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Sardahaee, F. S., Holmen, T. L., Micali, N., & Kvaloy, K. (2017). Effects of single genetic variants and polygenic obesity risk scores on disordered eating in adolescents – The HUNT study. Appetite, 118, 8–16.
Abstract: PURPOSE: Improving the understanding of the role of genetic risk on disordered eating (DE). METHODS: A case-control study including 1757 (F: 979, M: 778) adolescents (aged 13-19 years) from the Nord-Trondelag Health Study (HUNT), an ethnically homogenous Norwegian population based study. Cases and controls were defined using a shortened version of the Eating Attitude Test. Logistic regression was employed to test for associations between DE phenotypes and 24 obesity and eating disorder susceptibility SNPs, and the joint effect of a subset of these in a genetic risk score (GRS). RESULTS: COMT was shown to be associated with poor appetite/undereating (OR: 0.6, CI 95%: 0.43-0.83, p = 0.002). Independent of obesity associations, the weighted GRS was associated to overeating in 13-15 year old females (OR: 2.07, CI 95%: 1.14-3.76, p = 0.017). Additionally, a significant association was observed between the GRS and loss of control over eating in the total sample (OR: 1.62, CI 95%: 1.01-2.61, p = 0.046). CONCLUSIONS: The COMT variant (rs4680) was associated with poor appetite/undereating. Our study further confirms prior findings that obesity risk also confers risk for loss of control over eating; and overeating amongst girls.
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Lu, X., Peloso, G. M., Liu, D. J., Wu, Y., Zhang, H., Zhou, W., et al. (2017). Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease (Vol. 49).
Abstract: Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.
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Liu, D. J., Peloso, G. M., Yu, H., Butterworth, A. S., Wang, X., Mahajan, A., et al. (2017). Exome-wide association study of plasma lipids in >300,000 individuals. Nat Genet, 49(12), 1758–1766.
Abstract: We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
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Ueland, T., Laugsand, L. E., Vatten, L. J., Janszky, I., Platou, C., Michelsen, A. E., et al. (2017). Extracellular matrix markers and risk of myocardial infarction: The HUNT Study in Norway. Eur J Prev Cardiol, 24(11), 1161–1167.
Abstract: Aims Extracellular matrix remodelling may influence atherosclerotic progression and plaque stability. We hypothesized that evaluation of extracellular matrix markers, with potentially different roles during atherogenesis, could provide information on underlying mechanisms and risk of myocardial infarction (MI) in apparently healthy individuals. Methods We conducted a case-control study nested within the population-based HUNT2 cohort in Norway. A total of 58,761 men and women, free of known cardiovascular disease, were followed for a first MI. During 11.3 years of follow-up, 1587 incident MIs were registered, and these cases were compared with 3959 age- and sex-matched controls. Circulating levels of the ECM proteins CD147 (ECM metalloproteinase inducer; EMMPRIN), cartilage oligomeric matrix protein (COMP: thrombospondin-5) and YKL-40 (chitinase-3-like-1) were measured by enzyme immunoassays. Results We found an inverse association between COMP (quartile (Q) 4 vs. Q1: hazard ratio 0.81 (95% confidence interval: 0.67-0.98)) and YKL-40 (Q4 vs. Q1: hazard ratio 0.77 (0.62-0.95)) with incidence of MI after full multivariable adjustment. Serum CD147 was not associated with MI risk in adjusted analysis. Conclusion High levels of COMP and YKL-40 were associated with lower risk of incident MI, suggesting a potential beneficial role in promoting plaque stability in individuals without incident cardiovascular disease.
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Li, J., Wu, B., Selbaek, G., Krokstad, S., & Helvik, A. - S. (2017). Factors associated with consumption of alcohol in older adults – a comparison between two cultures, China and Norway: the CLHLS and the HUNT-study. BMC Geriatr, 17(1), 172.
Abstract: BACKGROUND: There is little knowledge about the consumption of alcohol among Chinese and Norwegian older adults aged 65 years and over. The aim of this study was to investigate the prevalence and factors related to alcohol consumption among older adults in China and Norway. METHODS: The Chinese Longitudinal Healthy Longevity Survey (CLHLS) data in 2008-2009 conducted in China and The Nord-Trondelag Health Study data in 2006-2008 (HUNT3) conducted in Norway were used. Mulitvariable logistic regression was used to test the factors related to alcohol consumption. RESULTS: The prevalence of participants who drink alcohol in the Chinese and Norwegian sample were 19.88% and 46.2%, respectively. The weighted prevalence of participants with consumption of alcohol in the Chinese sample of women and men were 7.20% and 34.14%, respectively. In the Norwegian sample, the prevalence of consumption of alcohol were 43.31% and 65.35% for women and men, respectively. Factors such as younger age, higher level of education, living in urban areas, living with spouse or partner, and better health status were related to higher likelihood of alcohol consumption among Norwegian older women and men; while reported better health status and poorer life satisfaction were related to higher likelihood of alcohol consumption among Chinese. In addition, rural males and older females with higher level of education were more likely to consume alcohol. CONCLUSION: The alcohol consumption patterns were quite different between China and Norway. Besides economic development levels and cultures in the two different countries, demographic characteristics, socioeconomic status, overall health status, and life satisfaction were associated with alcohol consumption as well.
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Machiela, M. J., Hofmann, J. N., Carreras-Torres, R., Brown, K. M., Johansson, M., Wang, Z., et al. (2017). Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma. Eur Urol, 72(5), 747–754.
Abstract: BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R(2)>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.
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Scelo, G., Purdue, M. P., Brown, K. M., Johansson, M., Wang, Z., Eckel-Passow, J. E., et al. (2017). Genome-wide association study identifies multiple risk loci for renal cell carcinoma. Nat Commun, 8, 15724.
Abstract: Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 x 10(-10)), 3p22.1 (rs67311347, P=2.5 x 10(-8)), 3q26.2 (rs10936602, P=8.8 x 10(-9)), 8p21.3 (rs2241261, P=5.8 x 10(-9)), 10q24.33-q25.1 (rs11813268, P=3.9 x 10(-8)), 11q22.3 (rs74911261, P=2.1 x 10(-10)) and 14q24.2 (rs4903064, P=2.2 x 10(-24)). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
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Justice, A. E., Winkler, T. W., Feitosa, M. F., Graff, M., Fisher, V. A., Young, K., et al. (2017). Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun, 8, 14977.
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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Graff, M., Scott, R. A., Justice, A. E., Young, K. L., Feitosa, M. F., Barata, L., et al. (2017). Genome-wide physical activity interactions in adiposity – A meta-analysis of 200,452 adults (Vol. 13).
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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Bjorngaard, J. H., Nordestgaard, A. T., Taylor, A. E., Treur, J. L., Gabrielsen, M. E., Munafo, M. R., et al. (2017). Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis. Int J Epidemiol, .
Abstract: Background: There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods: We performed Mendelian randomization analyses in the UK Biobank ( N = 114 029), the Norwegian HUNT study ( N = 56 664) and the Copenhagen General Population Study (CGPS) ( N = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies. Results: Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI: -0.002, 0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.16 cups per day, 95% CI: 0.11, 0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers or that the coffee-related variants were associated with cigarette consumption. Conclusions: Higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking.
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Alsnes, I. V., Vatten, L. J., Fraser, A., Bjorngaard, J. H., Rich-Edwards, J., Romundstad, P. R., et al. (2017). Hypertension in Pregnancy and Offspring Cardiovascular Risk in Young Adulthood: Prospective and Sibling Studies in the HUNT Study (Nord-Trondelag Health Study) in Norway (Vol. 69).
Abstract: Women with hypertensive disorders in pregnancy are at increased lifetime risk for cardiovascular disease. We examined the offspring's cardiovascular risk profile in young adulthood and their siblings' cardiovascular risk profile. From the HUNT study (Nord-Trondelag Health Study) in Norway, 15 778 participants (mean age: 29 years), including 210 sibling groups, were linked to information from the Medical Birth Registry of Norway. Blood pressure, anthropometry, serum lipids, and C-reactive protein were assessed. Seven hundred and six participants were born after exposure to maternal hypertension in pregnancy: 336 mothers had gestational hypertension, 343 had term preeclampsia, and 27 had preterm preeclampsia. Offspring whose mothers had hypertension in pregnancy had 2.7 (95% confidence interval, 1.8-3.5) mm Hg higher systolic blood pressure, 1.5 (0.9-2.1) mm Hg higher diastolic blood pressure, 0.66 (0.31-1.01) kg/m2 higher body mass index, and 1.49 (0.65-2.33) cm wider waist circumference, compared with offspring of normotensive pregnancies. Similar differences were observed for gestational hypertension and term preeclampsia. Term preeclampsia was also associated with higher concentrations of non-high-density lipoprotein cholesterol (0.14 mmol/L, 0.03-0.25) and triglycerides (0.13 mmol/L, 0.06-0.21). Siblings born after a normotensive pregnancy had nearly identical risk factor levels as siblings born after maternal hypertension. Offspring born after maternal hypertension in pregnancy have a more adverse cardiovascular risk profile in young adulthood than offspring of normotensive pregnancies. Their siblings, born after a normotensive pregnancy, have a similar risk profile, suggesting that shared genes or lifestyle may account for the association, rather than an intrauterine effect. All children of mothers who have experienced hypertension in pregnancy may be at increased lifetime risk of cardiovascular disease.
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Theofylaktopoulou, D., Midttun, O., Ueland, P. M., Meyer, K., Fanidi, A., Zheng, W., et al. (2017). Impaired functional vitamin B6 status is associated with increased risk of lung cancer. Int J Cancer, .
Abstract: Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4thvs.1st ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.
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Zhou, W., Fritsche, L. G., Das, S., Zhang, H., Nielsen, J. B., Holmen, O. L., et al. (2017). Improving power of association tests using multiple sets of imputed genotypes from distributed reference panels. Genet Epidemiol, 41(8), 744–755.
Abstract: The accuracy of genotype imputation depends upon two factors: the sample size of the reference panel and the genetic similarity between the reference panel and the target samples. When multiple reference panels are not consented to combine together, it is unclear how to combine the imputation results to optimize the power of genetic association studies. We compared the accuracy of 9,265 Norwegian genomes imputed from three reference panels-1000 Genomes phase 3 (1000G), Haplotype Reference Consortium (HRC), and a reference panel containing 2,201 Norwegian participants from the population-based Nord Trondelag Health Study (HUNT) from low-pass genome sequencing. We observed that the population-matched reference panel allowed for imputation of more population-specific variants with lower frequency (minor allele frequency (MAF) between 0.05% and 0.5%). The overall imputation accuracy from the population-specific panel was substantially higher than 1000G and was comparable with HRC, despite HRC being 15-fold larger. These results recapitulate the value of population-specific reference panels for genotype imputation. We also evaluated different strategies to utilize multiple sets of imputed genotypes to increase the power of association studies. We observed that testing association for all variants imputed from any panel results in higher power to detect association than the alternative strategy of including only one version of each genetic variant, selected for having the highest imputation quality metric. This was particularly true for lower frequency variants (MAF < 1%), even after adjusting for the additional multiple testing burden.
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Mauseth, S. A., Skurtveit, S., Langhammer, A., & Spigset, O. (2017). Incidence of and factors associated with anticholinergic drug use among Norwegian women with urinary incontinence. Int Urogynecol J, .
Abstract: INTRODUCTION AND HYPOTHESIS: The aims of this study were to investigate patterns of prescribing anticholinergic drugs among women with urinary incontinence (UI) and to identify factors associated with prescription of these drugs. METHODS: We analysed questionnaire data on UI from 21,735 women older than 20 years who participated in a cross-sectional population-based study in Nord-Trondelag county, Norway (the HUNT study). These data were linked at the individual level to a national prescription database, and analysed using a multivariate logistic regression model. RESULTS: Among the women with UI, 4.5% had been prescribed an anticholinergic drug during the previous 12 months. Prescription was most frequent in women with urge UI (10.5%) and mixed UI (7.0%). Of women with UI without treatment with an anticholinergic drug, 1.8% obtained such a prescription during the subsequent 12 months, corresponding to 3.1% of women with urge UI and 3.0% of women with mixed UI. Characteristics significantly associated with starting treatment were age above 50 years, urge or mixed UI, severe or very severe symptoms, consumption of four or more cups of coffee per day, and having visited a doctor for UI. No association was found with marital status, parity, smoking, alcohol, body mass index or anxiety/depression. CONCLUSIONS: In this population-based study, 4.5% of women with UI were prescribed an anticholinergic drug, and the 12-month incidence of starting treatment was 1.8%. Age above 50 years, urge or mixed UI, severe symptoms, high coffee consumption and having visited a doctor for UI were factors associated with first-time drug prescription.
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Hellevik, A. I., Johnsen, M. B., Langhammer, A., Fenstad, A. M., Furnes, O., Storheim, K., et al. (2017). Incidence of total hip or knee replacement due to osteoarthritis in relation to thyroid function: a prospective cohort study (The Nord-Trondelag Health Study). BMC Musculoskelet Disord, 18(1), 201.
Abstract: BACKGROUND: To study whether thyroid function was associated with risk of hip or knee replacement due to primary osteoarthritis. METHODS: In a prospective cohort study, data from the second and third survey of the Nord-Trondelag Health Study were linked to the Norwegian Arthroplasty Register in order to identify total hip or knee replacement as a result of primary osteoarthritis. RESULTS: Among 37 891 participants without previously known thyroid disease we recorded 978 total hip replacements (THRs) and 538 total knee replacements (TKRs) during a median follow-up time of 15.7 years. The analyses were adjusted for sex, age, BMI (body mass index), smoking, physical activity and diabetes. We did not find any association between TSH (thyroid stimulating hormone) and THR or TKR due to osteoarthritis. Neither were changes in TSH over time, or overt hypo- or hyperthyroidism, associated with incidence of THR or TKR. CONCLUSION: No association was found between thyroid function and hip or knee joint replacement due to osteoarthritis.
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Folling, I. S., Kulseng, B., Midthjell, K., Rangul, V., & Helvik, A. - S. (2017). Individuals at high risk for type 2 diabetes invited to a lifestyle program: characteristics of participants versus non-participants (the HUNT Study) and 24-month follow-up of participants (the VEND-RISK Study). BMJ Open Diabetes Res Care, 5(1), e000368.
Abstract: OBJECTIVE: Prevention of type 2 diabetes mellitus is possible through lifestyle programs, but the effect depends on the program's content, resources, and setting. Lifestyle programs are often confronted with high rates of non-participation and attrition. This study invited individuals at high risk for type 2 diabetes to a lifestyle program in the Norwegian primary healthcare setting. The aims were to investigate possible differences in characteristics between participants and non-participants and to study the effect of the lifestyle program at 24-month follow-up for participants. RESEARCH DESIGN AND METHODS: Individuals identified at high risk for type 2 diabetes during the third survey of the Nord-Trondelag Health Study (HUNT3) from two municipalities (n=332) were invited to a lifestyle program (the VEND-RISK Study). A cross-sectional design was used to explore if the participants' characteristics differed from non-participants. A non-randomized, single-arm, pre-post examination was used to examine the effect of the lifestyle program on participants' characteristics at 24-month follow-up. RESULTS: Of all individuals at high risk for type 2 diabetes invited to the lifestyle program, 86% (287/332) declined to participate. Non-participating women had fewer years of education (p<0.001), compared with participating women. For men, no differences were seen between non-participants and participants. Among all participants (n=45) at 24-month follow-up, none had developed type 2 diabetes, and HbA1c (p<0.001) had decreased significantly. There was a small reduction in mean body mass index from baseline to 24 months that was not statistically significant. For women, waist circumference (-4.0 cm, p<0.001) decreased significantly. CONCLUSIONS: Future research regarding individuals at high risk for type 2 diabetes in the primary healthcare lifestyle program should focus on how to promote recruitment of women with low education. Participants attending this study's lifestyle program improved their cardiometabolic markers. CLINICAL TRIALS REGISTRATION: NCT01135901; Results.
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Sen, A., Opdahl, S., Strand, L. B., Vatten, L. J., Laugsand, L. E., & Janszky, I. (2017). Insomnia and the Risk of Breast Cancer: The HUNT Study. Psychosom Med, 79(4), 461–468.
Abstract: OBJECTIVE: The association of insomnia with subsequent breast cancer risk is largely unknown. Therefore, we assessed whether different symptoms of insomnia and their combination are associated with incident breast cancer in a large population-based study. METHODS: In a prospective cohort study, 33,332 women were followed to monitor the occurrence of their first invasive breast cancer identified by the Cancer Registry of Norway. Insomnia symptoms including () nonrestorative sleep and () difficulty initiating and () maintaining sleep were self-reported using a study specific measure reflecting the current Diagnostic and Statistical Manual of Mental Disorders criteria. Hazard ratios and 95% confidence intervals were calculated using multiadjusted Cox proportional hazards models. RESULTS: A total of 862 incident breast cancer cases occurred during a mean follow-up of 14.7 years. No consistent association was observed between the individual insomnia symptoms and breast cancer risk. However, compared to women reporting no insomnia complaints, those who reported having all three aspects of insomnia simultaneously were at increased risk (hazard ratio, 2.38; 95% confidence interval = 1.11-5.09). CONCLUSION: Our results suggest that having only some aspects of insomnia may not predispose someone to breast cancer. In contrast, experiencing all insomnia symptoms simultaneously might confer considerable excess risk.
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Skaaby, T., Taylor, A. E., Jacobsen, R. K., Paternoster, L., Thuesen, B. H., Ahluwalia, T. S., et al. (2017). Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium. Sci Rep, 7(1), 2224.
Abstract: Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0.68, 95% confidence interval (CI): 0.61, 0.76; P < 0.001) and allergic sensitization (OR = 0.74, 95% CI: 0.64, 0.86; P < 0.001), but similar asthma risk (OR = 1.00, 95% CI: 0.91, 1.09; P = 0.967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0.958, 95% CI: 0.920, 0.998; P = 0.041), a lower risk of allergic sensitization (OR = 0.92, 95% CI: 0.84, 1.02; P = 0.117), but higher risk of asthma (OR = 1.06, 95% CI: 1.01, 1.11; P = 0.020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.
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Thorstensen, K., Kvitland, M. A., Irgens, W. O., Asberg, A., Borch-Iohnsen, B., Moen, T., et al. (2017). Iron loading in HFE p.C282Y homozygotes found by population screening: relationships to HLA-type and T-lymphocyte subsets. Scand J Clin Lab Invest, 77(7), 477–485.
Abstract: Iron loading in p.C282Y homozygous HFE hemochromatosis subjects is highly variable, and it is unclear what factors cause this variability. Finding such factors could aid in predicting which patients are at highest risk and require closest follow-up. The degree of iron loading has previously been associated with certain HLA-types and with abnormally low CD8 + cell counts in peripheral blood. In 183 Norwegian, p.C282Y homozygotes (104 men, 79 women) originally found through population screening we determined HLA type and measured total T-lymphocytes, CD4 + and CD8 + cells, and compared this with data on iron loading. In p.C282Y homozygous men, but not in homozygous women, we found that the presence of two HLA-A*03 alleles increased the iron load on average by approximately 2-fold compared to p.C282Y homozygous men carrying zero or one A*03 allele. On the other hand, the presence of two HLA-A*01 alleles, in male subjects, apparently reduced the iron loading. In p.C282Y homozygous individuals, the iron loading was increased if the CD8 + cell number was below the 25 percentile or if the CD4 + cell number was above the 75 percentile. This effect appeared to be additive to the effect of the number of HLA-A*03 alleles. Our data indicate that homozygosity for the HLA-A*03 allele significantly increases the risk of excessive iron loading in Norwegian p.C282Y homozygous male patients. In addition, low CD8 + cell number or high CD4 + cell number further increases the risk of excessive iron loading.
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Andre, B., Canhao, H., Espnes, G. A., Ferreira Rodrigues, A. M., Gregorio, M. J., Nguyen, C., et al. (2017). Is there an association between food patterns and life satisfaction among Norway's inhabitants ages 65 years and older? Appetite, 110, 108–115.
Abstract: The lack of information regarding older adults' health and lifestyles makes it difficult to design suitable interventions for people at risk of developing unhealth lifestyles. Therefore, there is a need to increase knowledge about older adults' food patterns and quality of life. Our aim was to determine associations among food patterns, anxiety, depression, and life satisfaction in Norwegian inhabitants ages 65+. The Nord-Trondelag Health Study (The HUNT Study) is a large, population-based cohort study that includes data for 125 000 Norwegian participants. The cohort used for this study is wave three of the study, consisting of 11 619 participants age 65 and over. Cluster analysis was used to categorize the participants based on similarities in food consumption; two clusters were identified based on similarities regarding food consumption among participants. Significant differences between the clusters were found, as participants in the healthy food-patterns cluster had higher life satisfaction and lower anxiety and depression than those in the unhealthy food-patterns cluster. The associations among food patterns, anxiety, depression, and life satisfaction among older adults show the need for increased focus on interactions among food patterns, food consumption, and life satisfaction among the elderly in order to explore how society can influence these patterns.
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Heuch, I., Heuch, I., Hagen, K., Mai, X. - M., Langhammer, A., & Zwart, J. - A. (2017). Is there an association between vitamin D status and risk of chronic low back pain? A nested case-control analysis in the Nord-Trondelag Health Study. BMJ Open, 7(11), e018521.
Abstract: OBJECTIVES: To explore potential associations between vitamin D status and risk of chronic low back pain (LBP) in a Norwegian cohort, and to investigate whether relationships depend on the season of blood sample collection. DESIGN: A nested case-control study in a prospective data set. SETTING: The Norwegian community-based Nord-Trondelag Health Study (HUNT). Data were collected in the HUNT2 (1995-1997) and HUNT3 (2006-2008) surveys. MAIN OUTCOME MEASURE: Chronic LBP, defined as LBP persisting at least 3 months continuously during the past year. PARTICIPANTS: Among individuals aged 19-55 years without LBP in HUNT2, a data set was generated including 1685 cases with LBP in HUNT3 and 3137 controls without LBP. METHODS: Blood samples from the participants collected in HUNT2 were analysed for serum 25-hydroxyvitamin D (25(OH)D) level. Associations with LBP in HUNT3 were evaluated by unconditional logistic regression analysis with adjustment for age, sex, work status, physical activity at work and in leisure time, education, smoking, and body mass index. RESULTS: No association between vitamin D status and risk of chronic LBP was found in the total data set (OR per 10 nmol/L 25(OH)D=1.01, 95% CI 0.97 to 1.06) or in individuals with blood samples collected in summer/autumn (OR per 10 nmol/L 25(OH)D=0.99, 95% CI 0.93 to 1.06). For blood samples drawn in winter/spring, associations differed significantly between women and men (p=0.004). Among women a positive association was seen (OR per 10 nmol/L 25(OH)D=1.11, 95% CI 1.02 to 1.20), but among men no significant association was observed (OR per 10 nmol/L 25(OH)D=0.90, 95% CI 0.81 to 1.01). CONCLUSIONS: Overall, no association between vitamin D status and risk of LBP was demonstrated. The association suggested in women for the winter/spring season cannot be regarded as established.
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Cai, Y., Hansell, A. L., Blangiardo, M., Burton, P. R., de Hoogh, K., Doiron, D., et al. (2017). Long-term exposure to road traffic noise, ambient air pollution, and cardiovascular risk factors in the HUNT and lifelines cohorts. Eur Heart J, 38(29), 2290–2296.
Abstract: Aims: Blood biochemistry may provide information on associations between road traffic noise, air pollution, and cardiovascular disease risk. We evaluated this in two large European cohorts (HUNT3, Lifelines). Methods and results: Road traffic noise exposure was modelled for 2009 using a simplified version of the Common Noise Assessment Methods in Europe (CNOSSOS-EU). Annual ambient air pollution (PM10, NO2) at residence was estimated for 2007 using a Land Use Regression model. The statistical platform DataSHIELD was used to pool data from 144 082 participants aged >/=20 years to enable individual-level analysis. Generalized linear models were fitted to assess cross-sectional associations between pollutants and high-sensitivity C-reactive protein (hsCRP), blood lipids and for (Lifelines only) fasting blood glucose, for samples taken during recruitment in 2006-2013. Pooling both cohorts, an inter-quartile range (IQR) higher day-time noise (5.1 dB(A)) was associated with 1.1% [95% confidence interval (95% CI: 0.02-2.2%)] higher hsCRP, 0.7% (95% CI: 0.3-1.1%) higher triglycerides, and 0.5% (95% CI: 0.3-0.7%) higher high-density lipoprotein (HDL); only the association with HDL was robust to adjustment for air pollution. An IQR higher PM10 (2.0 microg/m3) or NO2 (7.4 microg/m3) was associated with higher triglycerides (1.9%, 95% CI: 1.5-2.4% and 2.2%, 95% CI: 1.6-2.7%), independent of adjustment for noise. Additionally for NO2, a significant association with hsCRP (1.9%, 95% CI: 0.5-3.3%) was seen. In Lifelines, an IQR higher noise (4.2 dB(A)) and PM10 (2.4 microg/m3) was associated with 0.2% (95% CI: 0.1-0.3%) and 0.6% (95% CI: 0.4-0.7%) higher fasting glucose respectively, with both remaining robust to adjustment for air/noise pollution. Conclusion: Long-term exposures to road traffic noise and ambient air pollution were associated with blood biochemistry, providing a possible link between road traffic noise/air pollution and cardio-metabolic disease risk.
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Taylor, A. E., Carslake, D., de Mola, C. L., Rydell, M., Nilsen, T. I. L., Bjorngaard, J. H., et al. (2017). Maternal Smoking in Pregnancy and Offspring Depression: a cross cohort and negative control study. Sci Rep, 7(1), 12579.
Abstract: Previous reports suggest that offspring of mothers who smoke during pregnancy have greater risk of developing depression. However, it is unclear whether this is due to intrauterine effects. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK (N = 2,869), the Nord-Trondelag health study (HUNT) from Norway (N = 15,493), the Pelotas 1982 Birth Cohort Study from Brazil (N = 2,626), and the Swedish Sibling Health Cohort (N = 258 sibling pairs), we compared associations of maternal smoking during pregnancy and mother's partner's smoking during pregnancy with offspring depression and performed a discordant sibling analysis. In meta-analysis, maternal smoking during pregnancy was associated with higher odds of offspring depression (OR 1.20, 95% CI:1.08,1.34), but mother's partner's smoking during pregnancy was not (OR 1.05, 95% CI:0.94,1.17). However, there was only weak statistical evidence that the odds ratios for maternal and mother's partner's smoking differed from each other (p = 0.08). There was no clear evidence for an association between maternal smoking during pregnancy and offspring depression in the sibling analysis. Findings do not provide strong support for a causal role of maternal smoking during pregnancy in offspring depression, rather observed associations may reflect residual confounding relating to characteristics of parents who smoke.
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Ueland, T., Laugsand, L. E., Vatten, L. J., Janszky, I., Platou, C., Michelsen, A. E., et al. (2017). Monocyte/macrophage and T cell activation markers are not independently associated with MI risk in healthy individuals – results from the HUNT Study. Int J Cardiol, 243, 502–504.
Abstract: BACKGROUND: We hypothesized that circulating markers reflecting monocyte/macrophage and T cell activation are associated with increased risk of myocardial infarction (MI) in apparently healthy individuals. METHODS: Serum monocyte/macrophage and T cell activation markers soluble (s) CD163, sCD14, Gal3BP, sCD25 and sCD166 were analyzed by enzyme-immunoassay in a case-control study nested within the population-based HUNT2 cohort in Norway. Among 58,761 apparently healthy men and women followed a median 11.3years, 1587 incident MI cases were registered, and compared to 3959 age- and sex-matched controls. RESULTS: Higher serum sCD163 (Q4 vs. Q1 OR: 1.27, P-trend 0.002), sCD14 (Q4 vs. Q1 OR: 1.38, P-trend<0.001), and especially sCD25 (Q4 vs. Q1 OR: 1.45, P-trend<0.001), were associated with increased MI risk in the age-and sex adjusted models. However, after additional adjustment for cardiovascular risk factors these associations were strongly attenuated (Q4 vs Q1 ORs between 1.02 and 1.12, P-trends between 0.30 and 0.58). CONCLUSIONS: sCD163, sCD14 and sCD25 may reflect leukocyte activation and inflammatory mechanisms related to atherogenesis, but do not predict MI risk above and beyond conventional cardiovascular risk factors.
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Jorgensen, P., Langhammer, A., Krokstad, S., & Forsmo, S. (2017). Mortality in persons with undetected and diagnosed hypertension, type 2 diabetes, and hypothyroidism, compared with persons without corresponding disease – a prospective cohort study; The HUNT Study, Norway. BMC Fam Pract, 18(1), 98.
Abstract: BACKGROUND: Suggested strategies in reducing the impact of non-communicable diseases (NCD) are early diagnosing and screening. We have limited proof of benefit of population screening for NCD. Increased mortality in persons with diagnosed NCD has been shown for decades. However, mortality in undetected NCD has barely been studied. This paper explores whether all-cause mortality differed between persons with diagnosed hypothyroidism, type 2 diabetes (T2DM), and hypertension, compared with persons with undetected-, and with persons without the corresponding disease. METHODS: A prospective cohort study of the general population in Nord-Trondelag, Norway. Persons >/=20 years at baseline 1995-97 were followed until death or June 15, 2016. Cox proportional hazards models were used to compute age and multiple adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between disease status and all-cause mortality. The number of participants in the hypothyroidism study was 31,960, in the T2DM study 37,957, and in the hypertension study 63,371. RESULTS: Mortality was increased in persons with diagnosed type 2 diabetes and hypertension, compared to persons without corresponding disease; HR 1.69 (95% CI 1.55-1.84) and HR 1.23 (95% CI 1.09-1.39), respectively. Among persons with undetected T2DM, the HR was 1.21 (95% CI 1.08-1.37), whilst among undetected hypothyroidism and hypertension, mortality was not increased compared with persons without the diseases. Further, the association with mortality was stronger in persons with long duration of T2DM (HR 1.96 (95% CI 1.57-2.44)) and hypertension (HR 1.32 (95% CI 1.17-1.49)), compared with persons with short duration (HR 1.29 (1.09-1.53) and HR 1.16 (1.03-1-30) respectively). CONCLUSIONS: Mortality was increased in persons with diagnosed T2DM and hypertension, and in undetected T2DM, compared with persons without the diseases. The strength of the association with mortality in undetected T2DM was however lower compared with persons with diagnosed T2DM, and mortality was not increased in persons with undetected hypothyroidism and hypertension, compared with persons without the diseases. Thus, future research needs to test more thoroughly if early diagnosing of these diseases, such as general population screening, is beneficial for health.
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