| 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. |
- Fall, Tove, et al.
(författare)
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The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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| 3. |
- 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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