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Author (up) Bjorngaard, J.H.; Carslake, D.; Lund Nilsen, T.I.; Linthorst, A.C.E.; Davey Smith, G.; Gunnell, D.; Romundstad, P.R. url  doi
  Title Association of Body Mass Index with Depression, Anxiety and Suicide-An Instrumental Variable Analysis of the HUNT Study Type Journal Article
  Year 2015 Publication PloS one Abbreviated Journal PLoS One  
  Volume 10 Issue 7 Pages e0131708  
  Keywords HUNT3; Young-HUNT  
  Abstract OBJECTIVE: While high body mass index is associated with an increased risk of depression and anxiety, cumulative evidence indicates that it is a protective factor for suicide. The associations from conventional observational studies of body mass index with mental health outcomes are likely to be influenced by reverse causality or confounding by ill-health. In the present study, we investigated the associations between offspring body mass index and parental anxiety, depression and suicide in order to avoid problems with reverse causality and confounding by ill-health. METHODS: We used data from 32,457 mother-offspring and 27,753 father-offspring pairs from the Norwegian HUNT-study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale and suicide death from national registers. Associations between offspring and own body mass index and symptoms of anxiety and depression and suicide mortality were estimated using logistic and Cox regression. Causal effect estimates were estimated with a two sample instrument variable approach using offspring body mass index as an instrument for parental body mass index. RESULTS: Both own and offspring body mass index were positively associated with depression, while the results did not indicate any substantial association between body mass index and anxiety. Although precision was low, suicide mortality was inversely associated with own body mass index and the results from the analysis using offspring body mass index supported these results. Adjusted odds ratios per standard deviation body mass index from the instrumental variable analysis were 1.22 (95% CI: 1.05, 1.43) for depression, 1.10 (95% CI: 0.95, 1.27) for anxiety, and the instrumental variable estimated hazard ratios for suicide was 0.69 (95% CI: 0.30, 1.63). CONCLUSION: The present study's results indicate that suicide mortality is inversely associated with body mass index. We also found support for a positive association between body mass index and depression, but not for anxiety.  
  Address Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491, Trondheim, Norway  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  ISSN 1932-6203 ISBN Medium  
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  Notes PMID:26167892; PMC4500562 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1706  
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Author (up) Bjornland, T.; Langaas, M.; Grill, V.; Mostad, I.L. url  doi
  Title Assessing gene-environment interaction effects of FTO, MC4R and lifestyle factors on obesity using an extreme phenotype sampling design: Results from the HUNT study Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume 12 Issue 4 Pages e0175071  
  Keywords Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics; Body Mass Index; *Gene-Environment Interaction; Humans; *Life Style; Obesity/*genetics; *Phenotype; Receptor, Melanocortin, Type 4/*genetics; Waist-Hip Ratio  
  Abstract BACKGROUND: Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. METHODS: The HUNT study comprises health information on the population of Nord-Trondelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI >/= 35 kg/m2) in the third survey, HUNT3 (2006-08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995-97). RESULTS: Cross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20-40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive. CONCLUSIONS: In a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity.  
  Address Department of Clinical Nutrition and Speech-Language Therapy, Clinic of Clinical Services, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway  
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  Notes PMID:28384342; PMCID:PMC5383228 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1884  
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Author (up) Borte, S.; Winsvold, B.S.; Stensland, S.O.; Smastuen, M.C.; Zwart, J.-A. url  doi
  Title The effect of foetal growth restriction on the development of migraine and tension-type headache in adulthood. The HUNT Study Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume 12 Issue 4 Pages e0175908  
  Keywords Adult; Birth Weight; Female; Fetal Growth Retardation/epidemiology/*etiology; Gestational Age; Health Surveys; Humans; Infant, Newborn; Logistic Models; Male; Migraine Disorders/complications/*diagnosis/epidemiology; Norway/epidemiology; Odds Ratio; Pregnancy; Registries; Risk Factors; Tension-Type Headache/complications/*diagnosis/epidemiology; Young Adult  
  Abstract BACKGROUND: There is little knowledge about how factors early in life affect the development of migraine and tension-type headache. We aimed to examine whether growth restriction in utero is associated with development of migraine and frequent tension-type headache in adults. METHODS: The population-based Nord-Trondelag Health Study (HUNT 3) contained a validated headache questionnaire, which differentiated between migraine and tension-type headache. These data were linked to information on weight and gestational age at birth from the Norwegian Medical Birth Registry. In total 4557 females and 2789 males, aged 19-41 years, were included in this registry-based study. Participants were categorized as appropriate for gestational age (AGA, 10th-90th percentile), small for gestational age (SGA, 3rd-10th percentile) or very small for gestational age (VSGA, < 3rd percentile). Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for migraine and tension-type headache, with exposure being growth restriction at birth. RESULTS: The effect of growth restriction on migraine was modified by sex, with a significant association in males (p<0.001), but not in females (p = 0.20). In particular, males born VSGA were at increased risk of developing migraine (OR 2.73, 95% CI 1.63-4.58, p<0.001), with an intermediate risk among those born SGA (OR 1.50, 95% CI 0.96-2.35, p = 0.08) compared to those born AGA. There was no significant association between growth restriction and frequent TTH (p = 0.051). CONCLUSION: Growth restriction was associated with increased risk of migraine in adulthood among males, but not among females. This suggests that migraine might, in part, be influenced by early life events, and that males seem to be particularly vulnerable.  
  Address Department of Neurology, Oslo University Hospital, Oslo, Norway  
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  Notes PMID:28410431; PMCID:PMC5391957 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1885  
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Author (up) Bye, A.; Rosjo, H.; Aspenes, S.T.; Condorelli, G.; Omland, T.; Wisloff, U. url  doi
  Title Circulating microRNAs and aerobic fitness--the HUNT-Study Type Journal Article
  Year 2013 Publication PloS one Abbreviated Journal PLoS One  
  Volume 8 Issue 2 Pages e57496  
  Keywords Adult; Cohort Studies; *Exercise; Female; Humans; Male; MicroRNAs/*blood; Oxygen Consumption; *Physical Fitness  
  Abstract Aerobic fitness, measured as maximal oxygen uptake (VO2max), is a good indicator of cardiovascular health, and a strong predictor of cardiovascular mortality. Biomarkers associated with low VO2max may therefore represent potential early markers of future cardiovascular disease (CVD). The aim of this study was to assess whether circulating microRNAs (miRs) are associated with VO2max-level in healthy individuals. In a screening study, 720 miRs were measured in serum samples from healthy individuals (40-45 yrs) with high (n = 12) or low (n = 12) VO2max matched for gender, age and physical activity. Candiate miRs were validated in a second cohort of subjects with high (n = 38) or low (n = 38) VO2max. miR-210 and miR-222 were found to be higher in the low VO2max-group (p<0.05). In addition, miR-21 was increased in male participants with low VO2max (p<0.05). There were no correlations between traditional risk factors for CVD (blood pressure, cholesterol, smoking habit, or obesity) and miR-21, miR-210 and miR-222. DIANA-mirPath identified 611 potential gene-targets of miR-21, miR-210 and miR-222, and pathway analysis indicated alterations in several important signaling systems in subjects with low VO2max. Potential bias involve that blood was collected from non-fasting individuals, and that 8 performed exercise within 24 h before sampling. In conclusion, we found that miR-210, miR-21, and miR-222 were increased in healthy subjects with low VO2max. The lack of association between these three miRs, and other fitness related variables as well as traditional CVD risk factors, suggests that these miRs may have a potential as new independent biomarkers of fitness level and future CVD.  
  Address K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Anja.Bye@ntnu.no  
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  Notes PMID:23469005; PMC3585333 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1459  
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Author (up) Bye, A.; Vettukattil, R.; Aspenes, S.T.; Giskeodegard, G.F.; Gribbestad, I.S.; Wisloff, U.; Bathen, T.F. url  doi
  Title Serum levels of choline-containing compounds are associated with aerobic fitness level: the HUNT-study Type Journal Article
  Year 2012 Publication PloS one Abbreviated Journal PLoS One  
  Volume 7 Issue 7 Pages e42330  
  Keywords Choline/*blood; *Exercise; Female; Humans; Male; Oxygen Consumption; Reference Values  
  Abstract BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death worldwide, and the number of people at risk is continuously growing. New methods for early risk prediction are therefore needed to actuate prevention strategies before the individuals are diagnosed with CVD. Several studies report that aerobic fitness level, measured as maximal oxygen uptake (VO(2max)), is the single best predictor of future CVD mortality in healthy people. Based on this, we wanted to study differences between healthy individuals with a large difference in VO(2max)-level to identify new biomarkers of low aerobic fitness that may also have potential as early biomarkers of CVD risk. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples from 218 healthy individuals with a low VO(2max) (n = 108, 63 women) or high VO(2max) (n = 110, 64 women) were analysed with MR metabolomics. In addition, standard clinical-chemical analyses for glucose, lipids, liver enzymes, micro-CRP, and colorimetric analysis on circulating choline were performed. Individuals in the low VO(2max)-group had increased serum levels of free choline, decreased phosphatidylcholine, increased glucose and decreased unsaturated fatty acids compared to the individuals in the high VO(2max)-group. CONCLUSIONS/SIGNIFICANCE: Aerobic fitness dependent differences in serum levels of free choline and phosphatidylcholine are observed. They should be further studied as potential early markers of CVD risk.  
  Address Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway  
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  Notes PMID:22860113; PMC3408491 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1510  
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Author (up) De Ridder, K.A.A.; Pape, K.; Johnsen, R.; Holmen, T.L.; Westin, S.; Bjorngaard, J.H. url  doi
  Title Adolescent health and high school dropout: a prospective cohort study of 9000 Norwegian adolescents (the young-HUNT) Type Journal Article
  Year 2013 Publication PloS one Abbreviated Journal PLoS One  
  Volume 8 Issue 9 Pages e74954  
  Keywords  
  Abstract BACKGROUND: High school dropout is of major concern in the western world. Our aims were to estimate the risk of school dropout in adolescents following chronic somatic disease, somatic symptoms, psychological distress, concentration difficulties, insomnia or overweight and to assess to which extent the family contributes to the association between health and school dropout. METHODS: A population of 8950 school-attending adolescents (13-21 years) rated their health in the Young-HUNT 1 Study (90% response rate) in 1995-1997. High school dropout or completion, was defined with the Norwegian National Education Database in the calendar year the participant turned 24 years old. Parental socioeconomic status was defined by using linkages to the National Education Database, the National Insurance Administration and the HUNT2 Survey. We used logistic regression to estimate odds ratios and risk differences of high school dropout, both in the whole population and among siblings within families differentially exposed to health problems. RESULTS: All explored health dimensions were strongly associated with high school dropout. In models adjusted for parental socioeconomic status, the risk differences of school dropout according to health exposures varied between 3.6% (95% CI 1.7 to 5.5) for having >/= 1 somatic disease versus none and 11.7% (6.3 to 17.0) for being obese versus normal weight. The results from the analyses comparing differentially exposed siblings, confirmed these results with the exception of weaker associations for somatic diseases and psychological distress. School dropout was strongly clustered within families (family level conditional intraclass correlation 0.42). CONCLUSIONS: Adolescent health problems are markers for high school dropout, independent of parental socioeconomic status. Although school dropout it strongly related to family-level factors, also siblings with poor health have reduced opportunity to complete high school compared to healthy siblings. Public health policy should focus on ensuring young people with poor health the best attainable education.  
  Address Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway ; Department of Physical Medicine and Rehabilitation, Levanger Hospital, Nord-Trondelag Health Trust, Levanger, Norway  
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  Language English Summary Language Original Title  
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  ISSN 1932-6203 ISBN Medium  
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  Notes PMID:24086408; PMC3781164 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1455  
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Author (up) Haberg, A.K.; Hammer, T.A.; Kvistad, K.A.; Rydland, J.; Muller, T.B.; Eikenes, L.; Garseth, M.; Stovner, L.J. url  doi
  Title Incidental Intracranial Findings and Their Clinical Impact; The HUNT MRI Study in a General Population of 1006 Participants between 50-66 Years Type Journal Article
  Year 2016 Publication PLoS One Abbreviated Journal PloS one  
  Volume 11 Issue 3 Pages e0151080  
  Keywords Adolescent; Adult; Aged; *Brain; Brain Diseases/diagnosis/surgery; False Positive Reactions; Female; Humans; *Incidental Findings; *Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Neurosurgical Procedures; Referral and Consultation; Young Adult  
  Abstract OBJECTIVES: Evaluate types and prevalence of all, incidental, and clinically relevant incidental intracranial findings, i.e. those referred to primary physician or clinical specialist, in a cohort between 50 and 66 years from the Nord-Trondelag Health (HUNT) study. Types of follow-up, outcome of repeated neuroimaging and neurosurgical treatment were assessed. MATERIAL AND METHODS: 1006 participants (530 women) underwent MRI of the head at 1.5T consisting of T1 weighted sagittal IR-FSPGR volume, axial T2 weighted, gradient echo T2* weighted and FLAIR sequences plus time of flight cerebral angiography covering the circle of Willis. The nature of a finding and if it was incidental were determined from previous radiological examinations, patient records, phone interview, and/or additional neuroimaging. Handling and outcome of the clinically relevant incidental findings were prospectively recorded. True and false positives were estimated from the repeated neuroimaging. RESULTS: Prevalence of any intracranial finding was 32.7%. Incidental intracranial findings were present in 27.1% and clinically relevant findings in 15.1% of the participants in the HUNT MRI cohort. 185 individuals (18.4%) were contacted by phone about their findings. 40 participants (6.2%) underwent >/= 1 additional neuroimaging session to establish etiology. Most false positives were linked to an initial diagnosis of suspected glioma, and overall positive predictive value of initial MRI was 0.90 across different diagnoses. 90.8% of the clinically relevant incidental findings were developmental and acquired cerebrovascular pathologies, the remaining 9.2% were intracranial tumors, of which extra-axial tumors predominated. In total, 3.9% of the participants were referred to a clinical specialist, and 11.7% to their primary physician. 1.4% underwent neurosurgery/radiotherapy, and 1 (0.1%) experienced a procedure related postoperative deficit. CONCLUSIONS: In a general population between 50 and 66 years most intracranial findings on MRI were incidental, and >15% of the cohort was referred to clinical-follow up. Hence good routines for handling of findings need to be in place to ensure timely and appropriate handling.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway Editor  
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  Notes Haberg, Asta KristineHammer, Tommy ArildKvistad, Kjell ArneRydland, JanaMuller, Tomm BEikenes, LiveGarseth, MariStovner, Lars JacobengResearch Support, Non-U.S. Gov't2016/03/08 06:00PLoS One. 2016 Mar 7;11(3):e0151080. doi: 10.1371/journal.pone.0151080. eCollection 2016. Approved no  
  Call Number HUNT @ maria.stuifbergen @ Haberg2016 Serial 1743  
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Author (up) Heuch, I.; Heuch, I.; Hagen, K.; Zwart, J.-A. url  doi
  Title Do abnormal serum lipid levels increase the risk of chronic low back pain? The Nord-Trondelag Health Study Type Journal Article
  Year 2014 Publication PloS one Abbreviated Journal PLoS One  
  Volume 9 Issue 9 Pages e108227  
  Keywords HUNT2; HUNT3  
  Abstract BACKGROUND: Cross-sectional studies suggest associations between abnormal lipid levels and prevalence of low back pain (LBP), but it is not known if there is any causal relationship. OBJECTIVE: The objective was to determine, in a population-based prospective cohort study, whether there is any relation between levels of total cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides and the probability of experiencing subsequent chronic (LBP), both among individuals with and without LBP at baseline. METHODS: Information was collected in the community-based HUNT 2 (1995-1997) and HUNT 3 (2006-2008) surveys of an entire Norwegian county. Participants were 10,151 women and 8731 men aged 30-69 years, not affected by chronic LBP at baseline, and 3902 women and 2666 men with LBP at baseline. Eleven years later the participants indicated whether they currently suffered from chronic LBP. RESULTS: Among women without LBP at baseline, HDL cholesterol levels were inversely associated and triglyceride levels positively associated with the risk of chronic LBP at end of follow-up in analyses adjusted for age only. Adjustment for the baseline factors education, work status, physical activity, smoking, blood pressure and in particular BMI largely removed these associations (RR: 0.96, 95% CI: 0.85-1.07 per mmol/l of HDL cholesterol; RR: 1.16, 95% CI: 0.94-1.42 per unit of lg(triglycerides)). Total cholesterol levels showed no associations. In women with LBP at baseline and men without LBP at baseline weaker relationships were observed. In men with LBP at baseline, an inverse association with HDL cholesterol remained after complete adjustment (RR: 0.83, 95% CI: 0.72-0.95 per mmol/l). CONCLUSION: Crude associations between lipid levels and risk of subsequent LBP in individuals without current LBP are mainly caused by confounding with body mass. However, an association with low HDL levels may still remain in men who are already affected and possibly experience a higher pain intensity.  
  Address Department of Neurology and FORMI, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway  
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  Notes PMID:25233233; PMC4169450 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1646  
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Author (up) Johnsen, M.B.; Hellevik, A.I.; Smastuen, M.C.; Langhammer, A.; Furnes, O.; Flugsrud, G.B.; Nordsletten, L.; Zwart, J.A.; Storheim, K. url  doi
  Title The mediating effect of body mass index on the relationship between smoking and hip or knee replacement due to primary osteoarthritis. A population-based cohort study (the HUNT Study) Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume 12 Issue 12 Pages e0190288  
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  Abstract To investigate the total effect of smoking on total hip or knee replacement (THR/TKR) due to primary osteoarthritis (OA) and to quantify the indirect effect of smoking through body mass index (BMI). Participants from the Nord-Trondelag Health Study (the HUNT Study) were linked to the Norwegian Arthroplasty Register to detect the first THR or TKR due to primary OA. A mediation analysis was used to decompose the total effect of smoking into a direct and indirect effect. BMI was considered a mediator in the analysis. All effects were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs). The indirect effect of smoking mediated through BMI was expressed as a percentage (proportion*100). In total 55 188 participants were followed up during 17.2 years (median). We identified 1322 THRs and 754 TKRs. For men, the total effect of current vs. never smoking revealed a decreased risk of THR (HR 0.59, 95% CI 0.46-0.76) and TKR (HR 0.47, 95% CI 0.32-0.66). For women, current smoking increased the risk of THR (HR 1.34, 95% CI 1.11-1.60). For men, 6% and 7% of the risk reduction for THR and TKR, respectively, was mediated by BMI. We found a negative association between smoking and THR or TKR for men. On the contrary, smoking was associated with increased risk of THR for women. Most of the effect of smoking on joint replacement risk remained unexplained by BMI.  
  Address Faculty of Medicine, University of Oslo, Oslo, Norway  
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  Notes PMID:29284048; PMCID:PMC5746263 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1933  
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Author (up) Johnson, M.P.; Brennecke, S.P.; East, C.E.; Goring, H.H.H.; Kent, J.W.J.; Dyer, T.D.; Said, J.M.; Roten, L.T.; Iversen, A.-C.; Abraham, L.J.; Heinonen, S.; Kajantie, E.; Kere, J.; Kivinen, K.; Pouta, A.; Laivuori, H.; Austgulen, R.; Blangero, J.; Moses, E.K. url  doi
  Title Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene Type Journal Article
  Year 2012 Publication PloS one Abbreviated Journal PLoS One  
  Volume 7 Issue 3 Pages e33666  
  Keywords Australia; Chromosomes, Human, Pair 2/*genetics; Cohort Studies; Computational Biology; Female; Finland; Gene Expression Regulation; Genetic Loci/*genetics; *Genetic Predisposition to Disease; Genome, Human/genetics; *Genome-Wide Association Study; Humans; Inhibin-beta Subunits/*genetics/metabolism; Norway; Polymorphism, Single Nucleotide/genetics; Pre-Eclampsia/*genetics; Pregnancy; Reproducibility of Results; Risk Factors; Sequence Analysis, DNA  
  Abstract Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58x10(-7), OR = 1.57; rs12711941, p = 4.26x10(-7), OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p<5.11x10(-7)). These SNPs reside in an intergenic region less than 15 kb downstream from the 3' terminus of the Inhibin, beta B (INHBB) gene on 2q14.2. They are in linkage disequilibrium (LD) with each other (r(2) = 0.92), but not (r(2)<0.80) with any other genotyped SNP +/-250 kb. DNA re-sequencing in and around the INHBB structural gene identified an additional 25 variants. Of the 21 variants that we successfully genotyped back in the case-control cohort the most significant association observed was for a third intergenic SNP (rs7576192, p = 1.48x10(-7), OR = 1.59) in strong LD with the two significant GWAS SNPs (r(2)>0.92). We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes +/-500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, approximately 250 kb centromeric to INHBB, and preeclampsia (p = 0.03). We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s).  
  Address Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America  
  Corporate Author FINNPEC Study Group Thesis  
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  ISSN 1932-6203 ISBN Medium  
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  Notes PMID:22432041; PMC3303857 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1534  
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Author (up) Kelly, M.A.; Rees, S.D.; Hydrie, M.Z.I.; Shera, A.S.; Bellary, S.; O'Hare, J.P.; Kumar, S.; Taheri, S.; Basit, A.; Barnett, A.H. url  doi
  Title Circadian gene variants and susceptibility to type 2 diabetes: a pilot study Type Journal Article
  Year 2012 Publication PloS one Abbreviated Journal PLoS One  
  Volume 7 Issue 4 Pages e32670  
  Keywords Circadian Rhythm Signaling Peptides and Proteins/*genetics; Diabetes Mellitus, Type 2/*genetics; Female; Gene Frequency; Genetic Association Studies; *Genetic Predisposition to Disease; Genotyping Techniques; Humans; Male; Pilot Projects; *Polymorphism, Single Nucleotide; Risk Factors  
  Abstract BACKGROUND: Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. METHODOLOGY/PRINCIPAL FINDINGS: The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66-0.86], p = 3.18 x 10(-5)), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07-1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01-1.08], p = 0.008 and OR = 0.95 [0.91-0.99], p = 0.015 respectively). CONCLUSIONS/SIGNIFICANCE: None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility.  
  Address College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. m.a.kelly@bham.ac.uk  
  Corporate Author SAT2D Consortium Thesis  
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  Notes PMID:22485135; PMC3317653 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1536  
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Author (up) Kvaloy, K.; Holmen, J.; Hveem, K.; Holmen, T.L. url  doi
  Title Genetic Effects on Longitudinal Changes from Healthy to Adverse Weight and Metabolic Status – The HUNT Study Type Journal Article
  Year 2015 Publication PLoS One Abbreviated Journal PloS one  
  Volume 10 Issue 10 Pages e0139632  
  Keywords HUNT2; HUNT3; Adolescent; Adult; Apolipoproteins A/genetics; Blood Glucose/analysis; Blood Pressure; Body Mass Index; Cholesterol, HDL/blood; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Metabolic Syndrome X/blood/*etiology/genetics; Middle Aged; Overweight/blood/*complications/*genetics; *Polymorphism, Single Nucleotide; Proteins/genetics; Receptors, Dopamine D2/genetics; Triglycerides/blood; Weight Gain; Young Adult  
  Abstract INTRODUCTION: The complexity of obesity and onset and susceptibility of cardio-metabolic disorders are still poorly understood and is addressed here through studies of genetic influence on weight gain and increased metabolic risk longitudinally. SUBJECTS/METHODS: Twenty seven previously identified obesity, eating disorder or metabolic risk susceptibility SNPs were tested for association with weight or metabolically related traits longitudinally in 3999 adults participating both in the HUNT2 (1995-97) and HUNT3 (2006-08) surveys. Regression analyses were performed with changes from normal weight to overweight/obesity or from metabolically healthy to adverse developments with regards to blood pressure, glucose, HDL cholesterol, triglycerides or metabolic syndrome as outcomes. Additionally, a sub-sample of 1380 adolescents was included for testing association of nine SNPs with longitudinal weight gain into young adulthood. RESULTS: The most substantial effect on BMI-based weight gain from normal to overweight/obesity in adults was observed for the DRD2 variant (rs6277)(OR: 0.79, 95% CI: 0.69-0.90, P = 3.9x10-4, adj. P = 0.015). DRD2 was not associated with BMI on a cross-sectional level. In the adolescent sample, FTO (rs1121980) was associated with change to overweight at adulthood in the combined male-female sample (OR: 1.27, 95% CI: 1.09-1.49, P = 3.0x10-3, adj. P = 0.019) and in females (OR: 1.53, 95% CI: 1.23-1.91, P = 1.8x10-4, adj. P = 0.003). When testing for association to longitudinal adverse developments with regard to blood pressure, blood lipids and glucose, only rs964184 (ZNF259/APOA5) was significantly associated to unfavourable triglyceride changes (OR: 1.66, 95% CI: 1.36-2.03, P = 5.7x10-7, adj. P = 0.001). Pleiotropic effects on metabolic traits, however, were observed for several genetic loci cross-sectionally, ZNF259/APOA5, LPL and GRB14 being the most important. CONCLUSIONS: DRD2 exhibits effects on weight gain from normal weight to overweight/obesity in adults, while, FTO is associated to weight gain from adolescence to young adulthood. Unhealthy longitudinal triglyceride development is strongly affected by ZNF259/APOA. Our main finding, linking the DRD2 variant directly to the longitudinal weight gain observed, has not previously been identified. It suggests a genetic pre-disposition involving the dopaminergic signalling pathways known to play a role in food reward and satiety linked mechanisms.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication HUNT Research Center, Department of Public Health and General Practice, Faculty of Medicine, Norwegi Editor  
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  Notes Kvaloy, KirstiHolmen, JosteinHveem, KristianHolmen, Turid Lingaaseng2015/10/09 06:00PLoS One. 2015 Oct 7;10(10):e0139632. doi: 10.1371/journal.pone.0139632. eCollection 2015. Approved no  
  Call Number HUNT @ maria.stuifbergen @ Kvaloy2015 Serial 1833  
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Author (up) Landmark, T.; Romundstad, P.R.; Borchgrevink, P.C.; Kaasa, S.; Dale, O. url  doi
  Title Longitudinal associations between exercise and pain in the general population--the HUNT pain study Type Journal Article
  Year 2013 Publication PloS one Abbreviated Journal PLoS One  
  Volume 8 Issue 6 Pages e65279  
  Keywords Age Factors; Exercise/*physiology; Humans; Linear Models; Longitudinal Studies; Pain/*physiopathology/*psychology; Prospective Studies; Questionnaires; Sex Factors  
  Abstract BACKGROUND: Population-based studies have reported conflicting findings on the relationship between physical activity and pain, and most studies reporting a relationship are cross sectional. Temporal relationships are therefore difficult to infer and associations may be subject to confounding from a variety of other factors. The aim of the current study was to investigate the association between exercise and pain longitudinally and to use within subjects analyses to remove between subjects confounding. METHODS: In the population-based HUNT 3 study, participants reported both pain and level of exercise. A random sub-sample of 6419 participants was in addition invited to report their last week pain and exercise every three months over a 12 month period (five measurements in total). We used multilevel mixed effects linear regression analyses to prospectively estimate the association between regular levels of exercise (measured in HUNT 3) and subsequent longitudinal reporting of pain. We also estimated within-subjects associations (i.e. the variation in pain as a function of variation in exercise, over time, within individuals) to avoid confounding from between subject factors. RESULTS: Among those invited to participate (N = 6419), 4219 subjects returned at least two questionnaires. Compared with subjects who reported no or light exercise, those who reported moderate levels of exercise or more at baseline, reported less pain in repeated measures over a 12 month period in analyses adjusted for age, sex,education and smoking. Adjusting for baseline level of pain distinctly attenuated the findings. Within subjects, an increase in exercise was accompanied by a concurrent reduction in intensity of pain. However, we found no indication that exercise level at one occasion was related to pain reporting three months later. CONCLUSION: This longitudinal population-based study indicates that exercise is associated with lower level of pain and that this association is close in time.  
  Address Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. tormod.landmark@ntnu.no  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
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  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23776464; PMC3680414 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1431  
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Author (up) Lier, R.; Mork, P.J.; Holtermann, A.; Nilsen, T.I. url  doi
  Title Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study, Norway Type Journal Article
  Year 2016 Publication PLoS One Abbreviated Journal PloS one  
  Volume 11 Issue 4 Pages e0153828  
  Keywords  
  Abstract The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995-97 and in 2006-08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Department of Public Health and General Practice, Norwegian University of Science and Technology, Tr Editor  
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  Notes Lier, RagnhildMork, Paul JarleHoltermann, AndreasNilsen, Tom Ivar Lundeng2016/04/16 06:00PLoS One. 2016 Apr 15;11(4):e0153828. doi: 10.1371/journal.pone.0153828. eCollection 2016. Approved no  
  Call Number HUNT @ maria.stuifbergen @ Lier2016 Serial 1765  
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Author (up) Loe, H.; Nes, B.M.; Wisloff, U. url  doi
  Title Predicting VO2peak from Submaximal- and Peak Exercise Models: The HUNT 3 Fitness Study, Norway Type Journal Article
  Year 2016 Publication PLoS One Abbreviated Journal PloS one  
  Volume 11 Issue 1 Pages e0144873  
  Keywords Adult; Body Weight; *Exercise Test; Female; Heart Rate; Humans; Linear Models; Male; Middle Aged; *Models, Biological; Norway; Oxygen Consumption/*physiology; Reproducibility of Results  
  Abstract PURPOSE: Peak oxygen uptake (VO2peak) is seldom assessed in health care settings although being inversely linked to cardiovascular risk and all-cause mortality. The aim of this study was to develop VO2peak prediction models for men and women based on directly measured VO2peak from a large healthy population. METHODS: VO2peak prediction models based on submaximal- and peak performance treadmill work were derived from multiple regression analysis. 4637 healthy men and women aged 20-90 years were included. Data splitting was used to generate validation and cross-validation samples. RESULTS: The accuracy for the peak performance models were 10.5% (SEE = 4.63 mLkg(-1)min(-1)) and 11.5% (SEE = 4.11 mLkg(-1)min(-1)) for men and women, respectively, with 75% and 72% of the variance explained. For the submaximal performance models accuracy were 14.1% (SEE = 6.24 mLkg(-1)min(-1)) and 14.4% (SEE = 5.17 mLkg(-1)min(-1)) for men and women, respectively, with 55% and 56% of the variance explained. The validation and cross-validation samples displayed SEE and variance explained in agreement with the total sample. Cross-classification between measured and predicted VO2peak accurately classified 91% of the participants within the correct or nearest quintile of measured VO2peak. CONCLUSION: Judicious use of the exercise prediction models presented in this study offers valuable information in providing a fairly accurate assessment of VO2peak, which may be beneficial for risk stratification in health care settings.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication K.G. Jebsen Center of Exercise in Medicine at Department of Circulation and Medical Imaging, Norwegi Editor  
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  Notes Loe, HenrikNes, Bjarne MWisloff, UlrikengResearch Support, Non-U.S. Gov't2016/01/23 06:00PLoS One. 2016 Jan 21;11(1):e0144873. doi: 10.1371/journal.pone.0144873. eCollection 2016. Approved no  
  Call Number HUNT @ maria.stuifbergen @ Loe2016 Serial 1767  
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Author (up) Nauman, J.; Aspenes, S.T.; Nilsen, T.I.L.; Vatten, L.J.; Wisloff, U. url  doi
  Title A prospective population study of resting heart rate and peak oxygen uptake (the HUNT Study, Norway) Type Journal Article
  Year 2012 Publication PloS one Abbreviated Journal PLoS One  
  Volume 7 Issue 9 Pages e45021  
  Keywords Adult; Female; Follow-Up Studies; Heart Rate/*physiology; Humans; Male; Middle Aged; Motor Activity; Norway; Oxygen Consumption/*physiology; Prospective Studies; Rest/*physiology; Time Factors  
  Abstract OBJECTIVES: We assessed the prospective association of resting heart rate (RHR) at baseline with peak oxygen uptake (VO(2peak)) 23 years later, and evaluated whether physical activity (PA) could modify this association. BACKGROUND: Both RHR and VO(2peak) are strong and independent predictors of cardiovascular morbidity and mortality. However, the association of RHR with VO(2peak) and modifying effect of PA have not been prospectively assessed in population studies. METHODS: In 807 men and 810 women free from cardiovascular disease both at baseline (1984-86) and follow-up 23 years later, RHR was recorded at both occasions, and VO(2peak) was measured by ergospirometry at follow-up. We used Generalized Linear Models to assess the association of baseline RHR with VO(2peak), and to study combined effects of RHR and self-reported PA on later VO(2peak). RESULTS: There was an inverse association of RHR at baseline with VO(2peak) (p<0.01). Men and women with baseline RHR greater than 80 bpm had 4.6 mL.kg(-1).min(-1) (95% confidence interval [CI], 2.8 to 6.3) and 1.4 mL.kg(-1).min(-1) (95% CI, -0.4 to 3.1) lower VO(2peak) at follow-up compared with men and women with RHR below 60 bpm at baseline. We found a linear association of change in RHR with VO(2peak) (p=0.03), suggesting that a decrease in RHR over time is likely to be beneficial for cardiovascular fitness. Participants with low RHR and high PA at baseline had higher VO(2peak) than inactive people with relatively high RHR. However, among participants with relatively high RHR and high PA at baseline, VO(2peak) was similar to inactive people with relatively low RHR. CONCLUSION: RHR is an important predictor of VO(2peak), and serial assessments of RHR may provide useful and inexpensive information on cardiovascular fitness. The results suggest that high levels of PA may compensate for the lower VO(2peak) associated with a high RHR.  
  Address K.G. Jebsen Center of Exercise in Medicine at Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Javaid.nauman@ntnu.no  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23028740; PMC3445602 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1558  
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Author (up) Palmer, N.D.; McDonough, C.W.; Hicks, P.J.; Roh, B.H.; Wing, M.R.; An, S.S.; Hester, J.M.; Cooke, J.N.; Bostrom, M.A.; Rudock, M.E.; Talbert, M.E.; Lewis, J.P.; Ferrara, A.; Lu, L.; Ziegler, J.T.; Sale, M.M.; Divers, J.; Shriner, D.; Adeyemo, A.; Rotimi, C.N.; Ng, M.C.Y.; Langefeld, C.D.; Freedman, B.I.; Bowden, D.W.; Voight, B.F.; Scott, L.J.; Steinthorsdottir, V.; Morris, A.P.; Dina, C.; Welch, R.P.; Zeggini, E.; Huth, C.; Aulchenko, Y.S.; Thorleifsson, G.; McCulloch, L.J.; Ferreira, T.; Grallert, H.; Amin, N.; Wu, G.; Willer, C.J.; Raychaudhuri, S.; McCarroll, S.A.; Langenberg, C.; Hofmann, O.M.; Dupuis, J.; Qi, L.; Segre, A.V.; van Hoek, M.; Navarro, P.; Ardlie, K.; Balkau, B.; Benediktsson, R.; Bennett, A.J.; Blagieva, R.; Boerwinkle, E.; Bonnycastle, L.L.; Bostrom, K.B.; Bravenboer, B.; Bumpstead, S.; Burtt, N.P.; Charpentier, G.; Chines, P.S.; Cornelis, M.; Couper, D.J.; Crawford, G.; Doney, A.S.F.; Elliott, K.S.; Elliott, A.L.; Erdos, M.R.; Fox, C.S.; Franklin, C.S.; Ganser, M.; Gieger, C.; Grarup, N.; Green, T.; Griffin, S.; Groves, C.J.; Guiducci, C.; Hadjadj, S.; Hassanali, N.; Herder, C.; Isomaa, B.; Jackson, A.U.; Johnson, P.R.V.; Jorgensen, T.; Kao, W.H.L.; Klopp, N.; Kong, A.; Kraft, P.; Kuusisto, J.; Lauritzen, T.; Li, M.; Lieverse, A.; Lindgren, C.M.; Lyssenko, V.; Marre, M.; Meitinger, T.; Midthjell, K.; Morken, M.A.; Narisu, N.; Nilsson, P.; Owen, K.R.; Payne, F.; Perry, J.R.B.; Petersen, A.-K.; Platou, C.; Proenca, C.; Prokopenko, I.; Rathmann, W.; Rayner, N.W.; Robertson, N.R.; Rocheleau, G.; Roden, M.; Sampson, M.J.; Saxena, R.; Shields, B.M.; Shrader, P.; Sigurdsson, G.; Sparso, T.; Strassburger, K.; Stringham, H.M.; Sun, Q.; Swift, A.J.; Thorand, B.; Tichet, J.; Tuomi, T.; van Dam, R.M.; van Haeften, T.W.; van Herpt, T.; van Vliet-Ostaptchouk, J.V.; Walters, G.B.; Weedon, M.N.; Wijmenga, C.; Witteman, J.; Bergman, R.N.; Cauchi, S.; Collins, F.S.; Gloyn, A.L.; Gyllensten, U.; Hansen, T.; Hide, W.A.; Hitman, G.A.; Hofman, A.; Hunter, D.J.; Hveem, K.; Laakso, M.; Mohlke, K.L.; Morris, A.D.; Palmer, C.N.A.; Pramstaller, P.P.; Rudan, I.; Sijbrands, E.; Stein, L.D.; Tuomilehto, J.; Uitterlinden, A.; Walker, M.; Wareham, N.J.; Watanabe, R.M.; Abecasis, G.R.; Boehm, B.O.; Campbell, H.; Daly, M.J.; Hattersley, A.T.; Hu, F.B.; Meigs, J.B.; Pankow, J.S.; Pedersen, O.; Wichmann, H.-E.; Barroso, I.; Florez, J.C.; Frayling, T.M.; Groop, L.; Sladek, R.; Thorsteinsdottir, U.; Wilson, J.F.; Illig, T.; Froguel, P.; van Duijn, C.M.; Stefansson, K.; Altshuler, D.; Boehnke, M.; McCarthy, M.I.; Soranzo, N.; Wheeler, E.; Glazer, N.L.; Bouatia-Naji, N.; Magi, R.; Randall, J.; Johnson, T.; Elliott, P.; Rybin, D.; Henneman, P.; Dehghan, A.; Hottenga, J.J.; Song, K.; Goel, A.; Egan, J.M.; Lajunen, T.; Doney, A.; Kanoni, S.; Cavalcanti-Proenca, C.; Kumari, M.; Timpson, N.J.; Zabena, C.; Ingelsson, E.; An, P.; O'Connell, J.; Luan, J.'an; Elliott, A.; McCarroll, S.A.; Roccasecca, R.M.; Pattou, F.; Sethupathy, P.; Ariyurek, Y.; Barter, P.; Beilby, J.P.; Ben-Shlomo, Y.; Bergmann, S.; Bochud, M.; Bonnefond, A.; Borch-Johnsen, K.; Bottcher, Y.; Brunner, E.; Bumpstead, S.J.; Chen, Y.-D.I.; Chines, P.; Clarke, R.; Coin, L.J.M.; Cooper, M.N.; Crisponi, L.; Day, I.N.M.; de Geus, E.J.C.; Delplanque, J.; Fedson, A.C.; Fischer-Rosinsky, A.; Forouhi, N.G.; Frants, R.; Franzosi, M.G.; Galan, P.; Goodarzi, M.O.; Graessler, J.; Grundy, S.; Gwilliam, R.; Hallmans, G.; Hammond, N.; Han, X.; Hartikainen, A.-L.; Hayward, C.; Heath, S.C.; Hercberg, S.; Hicks, A.A.; Hillman, D.R.; Hingorani, A.D.; Hui, J.; Hung, J.; Jula, A.; Kaakinen, M.; Kaprio, J.; Kesaniemi, Y.A.; Kivimaki, M.; Knight, B.; Koskinen, S.; Kovacs, P.; Kyvik, K.O.; Lathrop, G.M.; Lawlor, D.A.; Le Bacquer, O.; Lecoeur, C.; Li, Y.; Mahley, R.; Mangino, M.; Manning, A.K.; Martinez-Larrad, M.T.; McAteer, J.B.; McPherson, R.; Meisinger, C.; Melzer, D.; Meyre, D.; Mitchell, B.D.; Mukherjee, S.; Naitza, S.; Neville, M.J.; Oostra, B.A.; Orru, M.; Pakyz, R.; Paolisso, G.; Pattaro, C.; Pearson, D.; Peden, J.F.; Pedersen, N.L.; Perola, M.; Pfeiffer, A.F.H.; Pichler, I.; Polasek, O.; Posthuma, D.; Potter, S.C.; Pouta, A.; Province, M.A.; Psaty, B.M.; Rayner, N.W.; Rice, K.; Ripatti, S.; Rivadeneira, F.; Rolandsson, O.; Sandbaek, A.; Sandhu, M.; Sanna, S.; Sayer, A.A.; Scheet, P.; Seedorf, U.; Sharp, S.J.; Shields, B.; Sijbrands, E.J.G.; Silveira, A.; Simpson, L.; Singleton, A.; Smith, N.L.; Sovio, U.; Swift, A.; Syddall, H.; Syvanen, A.-C.; Tanaka, T.; Tonjes, A.; Uitterlinden, A.G.; van Dijk, K.W.; Varma, D.; Visvikis-Siest, S.; Vitart, V.; Vogelzangs, N.; Waeber, G.; Wagner, P.J.; Walley, A.; Ward, K.L.; Watkins, H.; Wild, S.H.; Willemsen, G.; Witteman, J.C.M.; Yarnell, J.W.G.; Zelenika, D.; Zethelius, B.; Zhai, G.; Zhao, J.H.; Zillikens, M.C.; Borecki, I.B.; Loos, R.J.F.; Meneton, P.; Magnusson, P.K.E.; Nathan, D.M.; Williams, G.H.; Silander, K.; Salomaa, V.; Smith, G.D.; Bornstein, S.R.; Schwarz, P.; Spranger, J.; Karpe, F.; Shuldiner, A.R.; Cooper, C.; Dedoussis, G.V.; Serrano-Rios, M.; Lind, L.; Palmer, L.J.; Franks, P.W.; Ebrahim, S.; Marmot, M.; Kao, W.H.L.; Pramstaller, P.P.; Wright, A.F.; Stumvoll, M.; Hamsten, A.; Buchanan, T.A.; Valle, T.T.; Rotter, J.I.; Siscovick, D.S.; Penninx, B.W.J.H.; Boomsma, D.I.; Deloukas, P.; Spector, T.D.; Ferrucci, L.; Cao, A.; Scuteri, A.; Schlessinger, D.; Uda, M.; Ruokonen, A.; Jarvelin, M.-R.; Waterworth, D.M.; Vollenweider, P.; Peltonen, L.; Mooser, V.; Sladek, R. url  doi
  Title A genome-wide association search for type 2 diabetes genes in African Americans Type Journal Article
  Year 2012 Publication PloS one Abbreviated Journal PLoS One  
  Volume 7 Issue 1 Pages e29202  
  Keywords Adult; African Americans/*genetics; Aged; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2/*ethnology/*genetics; Female; Genetic Predisposition to Disease; *Genome-Wide Association Study; Genotype; Humans; Male; Meta-Analysis as Topic; Middle Aged; Polymorphism, Single Nucleotide; Validation Studies as Topic  
  Abstract African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5x10(-8)). SNP rs7560163 (P = 7.0x10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5x10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.  
  Address Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America. nallred@wfubmc.edu  
  Corporate Author MAGIC Investigators Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
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  ISSN 1932-6203 ISBN Medium  
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  Notes PMID:22238593; PMC3251563 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1565  
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Author (up) Petursson H, Sigurdsson JA, Bentsson C, Nilsen TIL, Getz L   
  Title Body configuration as a predictor of mortality: Comparison of five anthropometric measures in a 12 year follow-up of the Norwegian HUNT 2 Study Type Journal Article
  Year 2011 Publication PLoS One. 2011 Abbreviated Journal  
  Volume 6(10) Issue Pages e26621. Epub 2011 Oct 20.  
  Keywords HUNT2  
  Abstract  
  Address  
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  Publisher Place of Publication Editor  
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  Notes HUNT_ID:1160. HUNT2 Approved no  
  Call Number Serial 1120  
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Author (up) Prior, J.C.; Naess, M.; Langhammer, A.; Forsmo, S. url  doi
  Title Ovulation Prevalence in Women with Spontaneous Normal-Length Menstrual Cycles – A Population-Based Cohort from HUNT3, Norway Type Journal Article
  Year 2015 Publication PLoS One Abbreviated Journal PloS one  
  Volume 10 Issue 8 Pages e0134473  
  Keywords HUNT3; Adult; Anovulation/blood/*epidemiology; Cohort Studies; Cross-Sectional Studies; Female; Humans; Luteal Phase; Menstrual Cycle; Middle Aged; Norway/epidemiology; *Ovulation; *Premenopause; Prevalence; Progesterone/blood  
  Abstract BACKGROUND: Ovulatory menstrual cycles are essential for women's fertility and needed to prevent bone loss. There is a medical/cultural expectation that clinically normal menstrual cycles are inevitably ovulatory. Currently within the general population it is unknown the proportion of regular, normal-length menstrual cycles that are ovulatory. Thus, the objective of this study was to determine the population point prevalence of ovulation in premenopausal, normally menstruating women. The null hypothesis was that such cycles are ovulatory. METHODS: This is a single-cycle, cross-sectional, population-based study-a sub-study of the HUNT3 health study in the semi-rural county (Nord Trondelag) in mid-Norway. Participants included >3,700 spontaneously (no hormonal contraception) menstruating women, primarily Caucasian, ages 20-49.9 from that county. Participation rate was 51.9%. All reported the date previous flow started. A single, random serum progesterone level was considered ovulatory if >/=9.54 nmol/L on cycle days 14 to -3 days before usual cycle length (CL). RESULTS: Ovulation was assessed in 3,168 women mean age 41.7 (interquartile range, [IQR] 36.8 to 45.5), cycle length 28 days (d) (IQR 28 to 28) and body mass index (BMI) 26.3 kg/m2 (95% CI 26.1 to 26.4). Parity was 95.6%, 30% smoked, 61.3% exercised regularly and 18% were obese. 1,545 women with a serum progesterone level on cycle days 14 to -3 were presumed to be in the luteal phase. Of these, 63.3% of women had an ovulatory cycle (n = 978) and 37% (n = 567) were anovulatory. Women with/ without ovulation did not differ in age, BMI, cycle day, menarche age, cigarette use, physical activity, % obesity or self-reported health. There were minimal differences in parity (96.7% vs. 94.5%, P = 0.04) and major differences in progesterone level (24.5 vs. 3.8 nmol/L, P = 0.001). CONCLUSION: Anovulation in a random population occurs in over a third of clinically normal menstrual cycles.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Centre for Menstrual Cycle and Ovulation Research, University of British Columbia, Vancouver, Canada Editor  
  Language Summary Language Original Title  
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  Notes Prior, Jerilynn CNaess, MaritLanghammer, ArnulfForsmo, SiriengResearch Support, Non-U.S. Gov't2015/08/21 06:00PLoS One. 2015 Aug 20;10(8):e0134473. doi: 10.1371/journal.pone.0134473. eCollection 2015. Approved no  
  Call Number HUNT @ maria.stuifbergen @ Prior2015 Serial 1855  
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Author (up) Rangul, V.; Sund, E.R.; Mork, P.J.; Roe, O.D.; Bauman, A. url  doi
  Title The associations of sitting time and physical activity on total and site-specific cancer incidence: Results from the HUNT study, Norway Type Journal Article
  Year 2018 Publication PloS one Abbreviated Journal PLoS One  
  Volume 13 Issue 10 Pages e0206015  
  Keywords  
  Abstract BACKGROUND: Sedentary behavior is thought to pose different risks to those attributable to physical inactivity. However, few studies have examined the association between physical activity and sitting time with cancer incidence within the same population. METHODS: We followed 38,154 healthy Norwegian adults in the Nord-Trondelag Health Study (HUNT) for cancer incidence from 1995-97 to 2014. Cox proportional hazards regression was used to estimate risk of site-specific and total cancer incidence by baseline sitting time and physical activity. RESULTS: During the 16-years follow-up, 4,196 (11%) persons were diagnosed with cancer. We found no evidence that people who had prolonged sitting per day or had low levels of physical activity had an increased risk of total cancer incidence, compared to those who had low sitting time and were physically active. In the multivariate model, sitting >/=8 h/day was associated with 22% (95% CI, 1.05-1.42) higher risk of prostate cancer compared to sitting <8 h/day. Further, men with low physical activity (</=8.3 MET-h/week) had 31% (95% CI, 1.00-1.70) increased risk of colorectal cancer (CRC) and 45% (95% CI, 1.01-2.09) increased risk of lung cancer compared to participants with a high physical activity (>16.6 MET-h/week). The joint effects of physical activity and sitting time the indicated that prolonged sitting time increased the risk of CRC independent of physical activity in men. CONCLUSIONS: Our findings suggest that prolonged sitting and low physical activity are positively associated with colorectal-, prostate- and lung cancer among men. Sitting time and physical activity were not associated with cancer incidence among women. The findings emphasizing the importance of reducing sitting time and increasing physical activity.  
  Address Prevention Research Collaboration, School of Public Health, University of Sydney, New South Wales, Sydney, Australia  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
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  Notes PMID:30352079; PMCID:PMC6198967 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2146  
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Author (up) Skalicka, V.; Ringdal, K.; Witvliet, M.I. url  doi
  Title Socioeconomic inequalities in mortality and repeated measurement of explanatory risk factors in a 25 years follow-up Type Journal Article
  Year 2015 Publication PloS one Abbreviated Journal PLoS One  
  Volume 10 Issue 4 Pages e0124690  
  Keywords HUNT1; HUNT2  
  Abstract BACKGROUND: Socioeconomic inequalities in mortality can be explained by different groups of risk factors. However, little is known whether repeated measurement of risk factors can provide better explanation of socioeconomic inequalities in health. Our study examines the extent to which relative educational and income inequalities in mortality might be explained by explanatory risk factors (behavioral, psychosocial, biomedical risk factors and employment) measured at two points in time, as compared to one measurement at baseline. METHODS AND FINDINGS: From the Norwegian total county population-based HUNT Study (years 1984-86 and 1995-1997, respectively) 61 513 men and women aged 25-80 (82.5% of all enrolled) were followed-up for mortality in 25 years until 2009, employing a discrete time survival analysis. Socioeconomic inequalities in mortality were observed. As compared to their highest socioeconomic counterparts, the lowest educated men had an OR (odds ratio) of 1.41 (95% CI 1.29-1.55) and for the lowest income quartile OR = 1.59 (1.48-1.571), for women OR = 1.35 (1.17-1.55), and OR = 1.40 (1.28-1.52), respectively. Baseline explanatory variables attenuated the association between education and income with mortality by 54% and 54% in men, respectively, and by 69% and 18% in women. After entering time-varying variables, this attainment increased to 63% and 59% in men, respectively, and to 25% (income) in women, with no improvement in regard to education in women. Change in biomedical factors and employment did not amend the explanation. CONCLUSIONS: Addition of a second measurement for risk factors provided only a modest improvement in explaining educational and income inequalities in mortality in Norwegian men and women. Accounting for change in behavior provided the largest improvement in explained inequalities in mortality for both men and women, as compared to measurement at baseline. Psychosocial factors explained the largest share of income inequalities in mortality for men, but repeated measurement of these factors contributed only to modest improvement in explanation. Further comparative research on the relative importance of explanatory pathways assessed over time is needed.  
  Address Department of Sociology and Political Science, Norwegian University of Science and Technology, Trondheim, Norway  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:25853571 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1683  
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Author (up) Skaug, E.A.; Nes, B.; Aspenes, S.T.; Ellingsen, O. url  doi
  Title Non-Smoking Tobacco Affects Endothelial Function in Healthy Men in One of the Largest Health Studies Ever Performed; The Nord-Trondelag Health Study in Norway; HUNT3 Type Journal Article
  Year 2016 Publication PLoS One Abbreviated Journal PloS one  
  Volume 11 Issue 8 Pages e0160205  
  Keywords  
  Abstract BACKGROUND: Oral tobacco (snuff) is taking a large market share in Scandinavia, especially with young users. However, long-term health effects are unknown. Small studies show association between snuff and reduced endothelial function, representing an early stage of vascular injury that often precedes manifest cardiovascular disease by several years. We therefore determined the associations between snuff and endothelial function in a large sample of healthy Norwegian men. METHODS AND DESIGN: In the Fitness substudy of the Nord-Trondelag Health Study (HUNT3), endothelial function was measured by flow-mediated dilation (FMD). Aerobic fitness was measured by peak oxygen uptake (VO2peak). A cross-sectional design including 1 592 self-reported healthy men compared these observations with records of present tobacco use, standard cardiovascular risk factors, and socioeconomic status, using general linear models. RESULTS: FMD was lower in snuff users (FMD: 4.12%, 3.63, 4.61) compared to non-users (FMD: 4.52%, 4.27, 4.78) after adjustment for age (difference: -0.57%, -1.12, -0.01). After further adjustment for potential confounders, FMD still tended to be lower in snuff users than in non-users (difference: -0.53%, -1.09, 0.02). This difference was even more pronounced in the inactive snuff users (-0.83%, -1.59, -0.06) and in the low fit snuff users (-0.74%, CI -0.55, 0.079). CONCLUSIONS: Oral tobacco is associated with a tendency towards reduced endothelial function, indicating vascular changes that precede cardiovascular disease. The strongest associations were found in men with low physical activity or reduced aerobic fitness.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication K. G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegia Editor  
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  Notes Skaug, Eli-AnneNes, BjarneAspenes, Stian ThoresenEllingsen, OyvindENG2016/08/05 06:00PLoS One. 2016 Aug 4;11(8):e0160205. doi: 10.1371/journal.pone.0160205. eCollection 2016. Approved no  
  Call Number HUNT @ maria.stuifbergen @ Skaug2016 Serial 1782  
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Author (up) Steinsbekk A, Rise MB, Bishop F, Lewith G   
  Title Predictors for adolescent visits to practitioners of complementary and alternative medicine in a total population (the Young-HUNT studies) Type Journal Article
  Year 2011 Publication PLoS ONE 6(10): e25719. doi:10.1371/jounral.pone.0025719