| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 3. |
- Nettleton, Jennifer A, et al.
(författare)
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Gene x dietary pattern interactions in obesity : analysis of up to 68 317 adults of European ancestry
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 24:16, s. 4728-4738
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
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| 4. |
- Hvidtfeldt, Ulla A., et al.
(författare)
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Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-Aged, and Older Adults
- 2010
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 121:14, s. 1589-1597
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Tidskriftsartikel (refereegranskat)abstract
- Background-Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men <40 years of age and in women <50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults. This study examined whether the beneficial effect of alcohol on coronary heart disease depends on age. Methods and Results-In this pooled analysis of 8 prospective studies from North America and Europe including 192 067 women and 74 919 men free of cardiovascular diseases, diabetes, and cancers at baseline, average daily alcohol intake was assessed at baseline with a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups; hazard ratios among moderately drinking men (5.0 to 29.9 g/d) 39 to 50, 50 to 59, and >= 60 years of age were 0.58 (95% confidence interval [CI], 0.36 to 0.93), 0.72 (95% CI, 0.60 to 0.86), and 0.85 (95% CI, 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference between abstainers and moderate consumers in younger adults (incidence rate difference, 45 per 100 000; 90% CI, 8 to 84) than in middle-aged (incidence rate difference, 64 per 100 000; 90% CI, 24 to 102) and older (incidence rate difference, 89 per 100 000; 90% CI, 44 to 140) adults. Similar results were observed in women. Conclusion-Alcohol is also associated with a decreased risk of coronary heart disease in younger adults; however, the absolute risk was small compared with middle-aged and older adults. (Circulation. 2010; 121: 1589-1597.)
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| 5. |
- Jakobsen, Marianne U, et al.
(författare)
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Major types of dietary fat and risk of coronary heart disease : a pooled analysis of 11 cohort studies.
- 2009
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 89:5, s. 1425-1432
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. OBJECTIVE: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. DESIGN: This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. RESULTS: During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. CONCLUSION: The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.
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| 7. |
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| 8. |
- Pukkala, Eero, et al.
(författare)
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Nordic biological specimen banks as basis for studies of cancer causes and control - more than 2 million sample donors, 25 million person years and 100 000 prospective cancers
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 46:3, s. 286-307
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at -20 degrees C to -135 degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.
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| 9. |
- Tolstrup, Janne S, et al.
(författare)
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Smoking and risk of coronary heart disease in younger, middle-aged, and older adults
- 2014
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Ingår i: American Journal of Public Health. - : AMER PUBLIC HEALTH ASSOC INC. - 0090-0036 .- 1541-0048. ; 104:1, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. We investigated associations of smoking and coronary heart disease (CHD) by age. Methods. Data came from the Pooling Project on Diet and Coronary Heart Disease (8 prospective studies, 1974-1996; n = 192 067 women and 74 720 men, aged 40-89 years). Results. During follow-up, 4326 cases of CHD were reported. Relative to never smokers, CHD risk among current smokers was highest in the youngest and lowest in the oldest participants. For example, among women aged 40 to 49 years the hazard ratio was 8.5 (95% confidence interval [CI] = 5.0, 14) and 3.1 (95% CI = 2.0, 4.9) among those aged 70 years or older. The largest absolute risk differences between current smokers and never smokers were observed among the oldest participants. Finally, the majority of CHD cases among smokers were attributable to smoking. For example, attributable proportions of CHD by age group were 88% (40-49 years), 81% (50-59 years), 71% for (60-69 years), and 68% (70+ years) among women who smoked. Conclusions. Among smokers, the majority of CHD cases are attributable to smoking in all age groups. Smoking prevention is important, irrespective of age.
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| 10. |
- Vedtofte, Mia Sadowa, et al.
(författare)
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Association between the intake of alpha-linolenic acid and the risk of CHD
- 2014
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 112:5, s. 735-743
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Tidskriftsartikel (refereegranskat)abstract
- The intake of the mainly plant-derived n-3 PUFA alpha-linolenic acid (ALA) has been reported to be associated with a lower risk of CHD. However, the results have been inconsistent. Therefore, the objective of the present study was to examine the association between the intake of ALA and the risk of CHD. Potential effect modification by the intake of long-chain n-3 PUFA (n-3 LCPUFA) was also investigated. Data from eight American and European prospective cohort studies including 148 675 women and 80 368 men were used. The outcome measure was incident CHD (CHD event and death). During 4-10 years of follow-up, 4493 CHD events and 1751 CHD deaths occurred. Among men, an inverse association (not significant) between the intake of ALA and the risk of CHD events and deaths was observed. For each additional gram of ALA consumed, a 15% lower risk of CHD events (hazard ratios (HR) 0.85, 95% CI 0.72, 1.01) and a 23% lower risk of CHD deaths (HR 0.77, 95% CI 0.58, 1.01) were observed. No consistent association was observed among women. No effect modification by the intake of n-3 LCPUFA was observed.
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