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Marouli, E., Graff, M., Medina-Gomez, C., Lo, K. S., Wood, A. R., Kjaer, T. R., et al. (2017). Rare and low-frequency coding variants alter human adult height. Nature, 542(7640), 186–190.
Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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(2017). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants (Vol. 389).
Abstract: BACKGROUND: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. METHODS: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. FINDINGS: We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7-128.3) in men and 122.3 mm Hg (121.0-123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9-79.5) for men and 76.7 mm Hg (75.9-77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4-27.1) in men and 20.1% (17.8-22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. INTERPRETATION: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe. FUNDING: Wellcome Trust.
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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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Bjorngaard, J. H., Vie, G. A., Janszky, I., & Vatten, L. J. (2017). Reply to Letter to the editor “Comments on cardiovascular mortality – Comparing risk factor associations within couples and in the total population – The HUNT Study”. Int J Cardiol, 242, 8.
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Safiri, S., & Ayubi, E. (2017). Comments on cardiovascular mortality – Comparing risk factor associations within couples and in the total population – The HUNT study (Vol. 242).
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Bjorngaard, J. H., Vie, G. A., Krokstad, S., Janszky, I., Romundstad, P. R., & Vatten, L. J. (2017). Cardiovascular mortality – Comparing risk factor associations within couples and in the total population – The HUNT Study. Int J Cardiol, 232, 127–133.
Abstract: BACKGROUND: To compare associations of conventional risk factors with cardiovascular death within couples and in the population as a whole. METHODS: We analysed baseline data (1995-97) from the HUNT2 Study in Norway linked to the national Causes of Death Registry. We compared risk within couples using stratified Cox regression. RESULTS: During 914776 person-years, 3964 cardiovascular deaths occurred, and 1658 of the deaths occurred among 1494 couples. There were consistently stronger associations of serum lipids and blood pressure with cardiovascular mortality within couples compared to the population as a whole. For instance, for systolic blood pressure (per 20mmHg), the hazard ratio (HR) within couples was 1.28 (95% confidence interval: 1.17, 1.40) compared to 1.16 (1.12, 1.20) in the total population, and for diastolic pressure (per 10mmHg), the corresponding HRs were 1.16 (1.07, 1.26) and 1.11 (1.08, 1.13). Anthropometric factors (BMI, waist circumference, waist-hip ratio) as well as diabetes, smoking, physical activity, and education, showed nearly identical positive associations within couples and in the total population. CONCLUSIONS: Prospective population studies may tend to slightly underestimate associations of these factors with cardiovascular mortality.
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Modalsli, E. H., Asvold, B. O., Romundstad, P. R., Langhammer, A., Hoff, M., Forsmo, S., et al. (2017). Psoriasis, fracture risk and bone mineral density: the HUNT Study, Norway. Br J Dermatol, 176(5), 1162–1169.
Abstract: BACKGROUND: An association between psoriasis and osteoporosis has been reported. OBJECTIVES: To investigate, in a large prospective population-based Norwegian study, whether psoriasis is associated with increased risk of forearm or hip fracture; to investigate the cross-sectional association between psoriasis and bone mineral density (BMD) T-score in a subpopulation. METHODS: Hospital-derived fracture data from Nord-Trondelag County (1995-2013) were linked to psoriasis information, BMD measurements and lifestyle factors from the third survey of the Nord-Trondelag Health Study 2006-08 (HUNT3); socioeconomic data from the National Education Database; and use of medication from the Norwegian Prescription Database. RESULTS: Among 48 194 participants in HUNT3, we found no increased risk of forearm or hip fracture in 2804 patients with self-reported psoriasis [overall age- and sex-adjusted hazard ratio 1.03, 95% confidence interval (CI) 0.82-1.31]. No clear association was found between psoriasis and mean BMD T-score; overall age- and sex-adjusted differences in total hip, femoral neck and lumbar spine BMD T-scores were 0.02 (95% CI -0.11 to 0.14), 0.05 (95% CI -0.06 to 0.17) and 0.07 (95% CI -0.09 to 0.24), respectively. No clear association was found between psoriasis and prevalent osteoporosis in either total hip, femoral neck or lumbar spine; overall age- and sex-adjusted odds ratio was 0.77 (95% CI 0.54-1.10). Associations did not change substantially after adjustment for education, smoking, systemic steroid use and body mass index. CONCLUSIONS: We found no association between psoriasis and risk of fracture. The study did not indicate reduced BMD T-score or higher prevalence of osteoporosis among patients with psoriasis.
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Zijlema, W., Cai, Y., Doiron, D., Mbatchou, S., Fortier, I., Gulliver, J., et al. (2017). Corrigendum to “Road traffic noise, blood pressure and heart rate: Pooled analyses of harmonized data from 88,336 participants” [Environ. Res. 151 (2016) 804-813] (Vol. 152).
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Quanjer, P. H., Ruppel, G. L., Langhammer, A., Krishna, A., Mertens, F., Johannessen, A., et al. (2017). Bronchodilator Response in FVC Is Larger and More Relevant Than in FEV1 in Severe Airflow Obstruction. Chest, 151(5), 1088–1098.
Abstract: BACKGROUND: Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity, and severity of respiratory impairment. METHODS: BDR test data were available from clinical patients in the Netherlands, New Zealand, and the United States (n = 15,278; female subjects, 51.7%) and from surveys in Canada, Norway, and five Latin-American countries (n = 16,250; female subjects, 54.7%). BDR calculated according to FEV1, FVC, and FEV1/FVC was expressed as absolute change, a percentage of the baseline level (% baseline), a percentage of the predicted value (% predicted), and z score. RESULTS: Change (Delta) in FEV1 and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; DeltaFEV1 was significantly lower in African Americans. In 1,106 subjects with low FEV1 (200-1,621 mL) the FEV1 increased by 12% to 44.7% relative to baseline but < 200 mL. Expressing BDR as a percentage of the predicted value or as a z score attenuated the bias and made the 200-mL criterion redundant, but reduced positive responses by half. DeltaFEV1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z scores or % predicted; DeltaFVC, however expressed, increased with the level of airflow obstruction. CONCLUSIONS: Expressing FEV1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1 or FVC as % predicted or as z scores eliminates this artifact and renders the required 200-mL minimum increase redundant. In severe airways obstruction DeltaFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials.
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Snekvik, I., Smith, C. H., Nilsen, T. I. L., Langan, S. M., Modalsli, E. H., Romundstad, P. R., et al. (2017). Obesity, Waist Circumference, Weight Change, and Risk of Incident Psoriasis: Prospective Data from the HUNT Study. J Invest Dermatol, 137(12), 2484–2490.
Abstract: Although psoriasis has been associated with obesity, there are few prospective studies with objective measures. We prospectively examined the effect of body mass index, waist circumference, waist-hip ratio, and 10-year weight change on the risk of developing psoriasis among 33,734 people in the population-based Nord-Trondelag Health Study (i.e., HUNT), Norway. During follow-up, 369 incident psoriasis cases occurred. Relative risk (RR) of psoriasis was estimated by Cox regression. One standard deviation higher body mass index, waist circumference, and waist-hip ratio gave RRs of 1.22 (95% confidence interval [CI] = 1.11-1.34), 1.26 (95% CI = 1.15-1.39), and 1.18 (95% CI = 1.07-1.31), respectively. Compared with normal weight participants, obese people had an RR of 1.87 (95% CI = 1.38-2.52), whereas comparing the fourth with the first quartile of waist circumference gave an RR of 1.95 (95% CI = 1.46-2.61). One standard deviation higher weight change gave an RR of 1.20 (95% CI = 1.07-1.35), and people who increased their body weight by 10 kg or more had an RR of 1.72 (95% CI = 1.15-2.58) compared with being weight stable. In conclusion, obesity and high abdominal fat mass doubles the risk of psoriasis, and long-term weight gain substantially increases psoriasis risk. Preventing weight gain and promoting maintenance of a normal body weight could reduce incidence of psoriasis.
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Nes, B. M., Gutvik, C. R., Lavie, C. J., Nauman, J., & Wisloff, U. (2017). Personalized Activity Intelligence (PAI) for Prevention of Cardiovascular Disease and Promotion of Physical Activity. Am J Med, 130(3), 328–336.
Abstract: PURPOSE: To derive and validate a single metric of activity tracking that associates with lower risk of cardiovascular disease mortality. METHODS: We derived an algorithm, Personalized Activity Intelligence (PAI), using the HUNT Fitness Study (n = 4631), and validated it in the general HUNT population (n = 39,298) aged 20-74 years. The PAI was divided into three sex-specific groups (</=50, 51-99, and >/=100), and the inactive group (0 PAI) was used as the referent. Hazard ratios for all-cause and cardiovascular disease mortality were estimated using Cox proportional hazard regressions. RESULTS: After >1 million person-years of observations during a mean follow-up time of 26.2 (SD 5.9) years, there were 10,062 deaths, including 3867 deaths (2207 men and 1660 women) from cardiovascular disease. Men and women with a PAI level >/=100 had 17% (95% confidence interval [CI], 7%-27%) and 23% (95% CI, 4%-38%) reduced risk of cardiovascular disease mortality, respectively, compared with the inactive groups. Obtaining >/=100 PAI was associated with significantly lower risk for cardiovascular disease mortality in all prespecified age groups, and in participants with known cardiovascular disease risk factors (all P-trends <.01). Participants who did not obtain >/=100 PAI had increased risk of dying regardless of meeting the physical activity recommendations. CONCLUSION: PAI may have a huge potential to motivate people to become and stay physically active, as it is an easily understandable and scientifically proven metric that could inform potential users of how much physical activity is needed to reduce the risk of premature cardiovascular disease death.
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Lie, A., Engdahl, B., Hoffman, H. J., Li, C. - M., & Tambs, K. (2017). Occupational noise exposure, hearing loss, and notched audiograms in the HUNT Nord-Trondelag hearing loss study, 1996-1998. Laryngoscope, 127(6), 1442–1450.
Abstract: OBJECTIVES/HYPOTHESIS: To study the prevalence and usefulness of audiometric notches in the diagnosis of noise-induced hearing loss (NIHL). STUDY DESIGN: Audiograms and data on noise exposure from 23,297 men and 26,477 women, aged 20 to 101 years, from the Nord-Trondelag Hearing Loss Study, 1996-1998. METHODS: The prevalence of four types of audiometric notches (Coles, Hoffman, Wilson) and 4 kHz notch were computed in relation to occupational noise exposure, age, sex, and report of recurrent ear infections. RESULTS: The prevalence of notches in the 3 to 6 kHz range (Wilson, Hoffman, and Coles) ranged from 50% to 60% in subjects without occupational noise exposure, and 60% to 70% in the most occupationally noise-exposed men. The differences were statistically significant only for bilateral notches. For 4 kHz notches, the prevalence varied from 25% in occupationally nonexposed to 35% in the most occupationally exposed men, and the differences were statistically significant for both bilateral and unilateral notches. For women, the prevalence of notches was lower than in men, especially for 4 kHz notches, and the differences between occupationally noise exposed and nonexposed were smaller. Recreational exposure to high music was not associated with notched audiograms. CONCLUSIONS: The detection of bilateral notches and unilateral 4 kHz notches is of some value in diagnosing NIHL, especially in men. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1442-1450, 2017.
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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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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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Karlsen, T., Nauman, J., Dalen, H., Langhammer, A., & Wisloff, U. (2017). The Combined Association of Skeletal Muscle Strength and Physical Activity on Mortality in Older Women: The HUNT2 Study. Mayo Clin Proc, 92(5), 710–718.
Abstract: OBJECTIVE: To assess the isolated and combined associations of leg and arm strength with adherence to current physical activity guidelines with all-cause and cause-specific mortality in healthy elderly women. PATIENTS AND METHODS: This was a prospective cohort study of 2529 elderly women (72.6+/-4.8 years) from the Norwegian Healthy survey of Northern Trondelag (second wave) (HUNT2) between August 15, 1995, and June 18, 1997, with a median of 15.6 years (interquartile range, 10.4-16.3 years) of follow-up. Chair-rise test and handgrip strength performances were assessed, and divided into tertiles. The hazard ratio (HR) of all-cause and cause-specific mortality by tertiles of handgrip strength and chair-rise test performance, and combined associations with physical activity were estimated by using Cox proportional hazard regression models. RESULTS: We observed independent associations of physical activity and the chair-rise test performance with all-cause and cardiovascular mortality, and between handgrip strength and all-cause mortality. Despite following physical activity guidelines, women with low muscle strength had increased risk of all-cause mortality (HR chair test, 1.37; 95% CI, 1.07-1.76; HR handgrip strength, 1.39; 95% CI, 1.05-1.85) and cardiovascular disease mortality (HR chair test, 1.57; 95% CI, 1.01-2.42). Slow chair-test performance was associated with all-cause (HR, 1.32; 95% CI, 1.16-1.51) and cardiovascular disease (HR, 1.41; 95% CI, 1.14-1.76) mortality. The association between handgrip strength and all-cause mortality was dose dependent (P value for trend <.01). CONCLUSION: Handgrip strength and chair-rise test performance predicted the risk of all-cause and CVD mortality independent of physical activity. Clinically feasible tests of skeletal muscle strength could increase the precision of prognosis, even in elderly women following current physical activity guidelines.
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Nauman, J., Nes, B. M., Lavie, C. J., Jackson, A. S., Sui, X., Coombes, J. S., et al. (2017). Prediction of Cardiovascular Mortality by Estimated Cardiorespiratory Fitness Independent of Traditional Risk Factors: The HUNT Study. Mayo Clin Proc, 92(2), 218–227.
Abstract: OBJECTIVE: To assess the predictive value of estimated cardiorespiratory fitness (eCRF) and evaluate the additional contribution of traditional risk factors in cardiovascular disease (CVD) mortality prediction. PARTICIPANTS AND METHODS: The study included healthy men (n=18,721) and women (n=19,759) aged 30 to 74 years. A nonexercise algorithm estimated cardiorespiratory fitness. Cox proportional hazards models evaluated the primary (CVD mortality) and secondary (all-cause, ischemic heart disease, and stroke mortality) end points. The added predictive value of traditional CVD risk factors was evaluated using the Harrell C statistic and net reclassification improvement. RESULTS: After a median follow-up of 16.3 years (range, 0.04-17.4 years), there were 3863 deaths, including 1133 deaths from CVD (734 men and 399 women). Low eCRF was a strong predictor of CVD and all-cause mortality after adjusting for established risk factors. The C statistics for eCRF and CVD mortality were 0.848 (95% CI, 0.836-0.861) and 0.878 (95% CI, 0.862-0.894) for men and women, respectively, increasing to 0.851 (95% CI, 0.839-0.863) and 0.881 (95% CI, 0.865-0.897), respectively, when adding clinical variables. By adding clinical variables to eCRF, the net reclassification improvement of CVD mortality was 0.014 (95% CI, -0.023 to 0.051) and 0.052 (95% CI, -0.023 to 0.127) in men and women, respectively. CONCLUSION: Low eCRF is independently associated with CVD and all-cause mortality. The inclusion of traditional clinical CVD risk factors added little to risk discrimination and did not improve the classification of risk beyond this simple eCRF measurement, which may be proposed as a practical and cost-effective first-line approach in primary prevention settings.
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Naicker, K., Overland, S., Johnson, J. A., Manuel, D., Skogen, J. C., Sivertsen, B., et al. (2017). Symptoms of anxiety and depression in type 2 diabetes: Associations with clinical diabetes measures and self-management outcomes in the Norwegian HUNT study. Psychoneuroendocrinology, 84, 116–123.
Abstract: OBJECTIVE: To determine if symptoms of depression and anxiety are differentially associated with clinical diabetes measures and self-management behaviours in individuals with Type 2 diabetes, and whether these associations vary by patient sex. RESEARCH DESIGN AND METHODS: A cross-sectional analysis using data from 2035 adults with Type 2 diabetes in the Nord-Trondelag Health Study. Multivariate logistic regression was used to explore associations between symptoms of depression and anxiety and waist girth, HDL cholesterol, systolic blood pressure, triglycerides, c-reactive protein, glycemic control, diet adherence, exercise, glucose monitoring, foot checks for ulcers, and the subjective patient experience. Analyses were stratified by sex. RESULTS: Depression was associated with a lower likelihood of avoiding saturated fats (OR=0.20 [95% CI: 0.06, 0.68]) and increased odds of physical inactivity (OR=1.69 [95% CI: 1.37, 2.72]). Anxiety was associated with increased odds of eating vegetables (OR=1.66 [95% CI: 1.02, 2.73]), and an over two-fold increase of feeling that having diabetes is difficult. In women, anxiety was associated with elevated c-reactive protein levels (OR=1.57 [95% CI: 1.05, 2.34]). In men, depressive symptoms were associated with elevated HbA1c (OR=5.00 [95% CI: 1.15, 8.23). CONCLUSIONS: Symptoms of depression and anxiety were differentially associated with some key diabetes-related measures. Our results suggest sex-specific differences with respect to two important clinical outcomes (i.e., anxiety and CRP in women and depression and glycemic control in men). These findings should alert practitioners to the importance of detection and management of psychological symptoms in individuals with Type 2 diabetes.
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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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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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Vindenes, H. K., Svanes, C., Lygre, S. H. L., Hollund, B. - E., Langhammer, A., & Bertelsen, R. J. (2017). Prevalence of, and work-related risk factors for, hand eczema in a Norwegian general population (The HUNT Study). Contact Dermatitis, 77(4), 214–223.
Abstract: BACKGROUND: Chemical exposures at work and at home may cause hand eczema. However, this has been scarcely described for Norway. OBJECTIVES: To investigate the prevalence of, and occupational risk factors for, hand eczema in Norway. METHODS: Among 50 805 respondents (aged >/=20 years) to the third Nord-Trondelag Health Study (HUNT3), 5757 persons reported ever having hand eczema, and 4206 answered a hand eczema questionnaire. RESULTS: The lifetime prevalences of hand eczema were 8.4% in men and 13.8% in women (p < 0.001), with onset at age </=10 years in 24% (men) and 20% (women), and onset at age >/=30 years in 37% (men) and 25% (women) (p < 0.001). Work-related hand eczema affected 4.8% of the population, and was most frequently associated with health/social work (29%) and occupational cleaning (20%) in women, and with farming (26%) and industrial occupations (27%) in men. Cleaning detergents (75%) and other chemicals (36%) were the most common exacerbating factors. CONCLUSIONS: The prevalence of hand eczema was 11.3%, and that of work-related hand eczema was 4.8%. Hand eczema was more common in women than in men, but with a later onset in men. Cleaning detergents were the most common aggravating factors. A large proportion of the Nord-Trondelag population is employed in farming, providing the possibility to identify farming as an important risk factor for hand eczema.
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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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Evensen, M., Lyngstad, T. H., Melkevik, O., Reneflot, A., & Mykletun, A. (2017). Adolescent mental health and earnings inequalities in adulthood: evidence from the Young-HUNT Study. J Epidemiol Community Health, 71(2), 201–206.
Abstract: BACKGROUND: Previous studies have shown that adolescent mental health problems are associated with lower employment probabilities and risk of unemployment. The evidence on how earnings are affected is much weaker, and few have addressed whether any association reflects unobserved characteristics and whether the consequences of mental health problems vary across the earnings distribution. METHODS: A population-based Norwegian health survey linked to administrative registry data (N=7885) was used to estimate how adolescents' mental health problems (separate indicators of internalising, conduct, and attention problems and total sum scores) affect earnings (>/=30 years) in young adulthood. We used linear regression with fixed-effects models comparing either students within schools or siblings within families. Unconditional quantile regressions were used to explore differentials across the earnings distribution. RESULTS: Mental health problems in adolescence reduce average earnings in adulthood, and associations are robust to control for observed family background and school fixed effects. For some, but not all mental health problems, associations are also robust in sibling fixed-effects models, where all stable family factors are controlled. Further, we found much larger earnings loss below the 25th centile. CONCLUSIONS: Adolescent mental health problems reduce adult earnings, especially among individuals in the lower tail of the earnings distribution. Preventing mental health problems in adolescence may increase future earnings.
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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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Webb, T. R., Erdmann, J., Stirrups, K. E., Stitziel, N. O., Masca, N. G. D., Jansen, H., et al. (2017). Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. J Am Coll Cardiol, 69(7), 823–836.
Abstract: BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits. CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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Asvold, B. O., Midthjell, K., Krokstad, S., Rangul, V., & Bauman, A. (2017). Prolonged sitting may increase diabetes risk in physically inactive individuals: an 11 year follow-up of the HUNT Study, Norway. Diabetologia, 60(5), 830–835.
Abstract: AIMS/HYPOTHESIS: We examined the association between sitting time and diabetes incidence, overall and by strata of leisure-time physical activity and BMI. METHODS: We followed 28,051 adult participants of the Nord-Trondelag Health Study (the HUNT Study), a population-based study, for diabetes incidence from 1995-1997 to 2006-2008 and estimated HRs of any diabetes by categories of self-reported total daily sitting time at baseline. RESULTS: Of 28,051 participants, 1253 (4.5%) developed diabetes during 11 years of follow-up. Overall, sitting >/=8 h/day was associated with a 17% (95% CI 2, 34) higher risk of developing diabetes compared with sitting </=4 h/day, adjusted for age, sex and education. However, the association was attenuated to a non-significant 9% (95% CI -5, 26) increase in risk after adjustment for leisure-time physical activity and BMI. The association between sitting time and diabetes risk differed by leisure-time physical activity (p Interaction = 0.01). Among participants with low leisure-time physical activity (</=2 h light activity per week and no vigorous activity), sitting 5-7 h/day and >/=8 h/day were associated with a 26% (95% CI 2, 57) and 30% (95% CI 5, 61) higher risk of diabetes, respectively, compared with sitting </=4 h/day. There was no corresponding association among participants with high leisure-time physical activity (>/=3 h light activity or >0 h vigorous activity per week). There was no statistical evidence that the association between sitting time and diabetes risk differed by obesity (p Interaction = 0.65). CONCLUSIONS/INTERPRETATION: Our findings suggest that total sitting time has little association with diabetes risk in the population as a whole, but prolonged sitting may contribute to an increased diabetes risk among physically inactive people.
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