Journal
NATURE MEDICINE
Volume 25, Issue 9, Pages 1390-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41591-019-0563-7
Keywords
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Funding
- SNIC through the Uppsala Multidisciplinary Center for Advanced Computational Science [b2016021, sens2017538]
- Swedish Society for Medical Research
- Swedish Research Council [2015-03327]
- Kjell and Marta Beijers Foundation
- Goran Gustafssons Foundation
- Marcus Borgstrom Foundation
- Ake Wiberg Foundation [M16-0210]
- Swedish Heart and Lung Foundation [20170484]
- Swedish Diabetes Foundation
- Science for Life Laboratory
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Visceral adipose tissue (VAT)-fat stored around the internal organs-has been suggested as an independent risk factor for cardiovascular and metabolic disease(1-3), as well as all-cause, cardiovascular-specific and cancer-specific mortality(4,5). Yet, the contribution of genetics to VAT, as well as its disease-related effects, are largely unexplored due to the requirement for advanced imaging technologies to accurately measure VAT. Here, we develop sex-stratified, nonlinear prediction models (coefficient of determination = 0.76; typical 95% confidence interval (CI) = 0.74-0.78) for VAT mass using the UK Biobank cohort. We performed a genome-wide association study for predicted VAT mass and identified 102 novel visceral adiposity loci. Predicted VAT mass was associated with increased risk of hypertension, heart attack/angina, type 2 diabetes and hyperlipidemia, and Mendelian randomization analysis showed visceral fat to be a causal risk factor for all four diseases. In particular, a large difference in causal effect between the sexes was found for type 2 diabetes, with an odds ratio of 7.34 (95% CI= 4.48-12.0) in females and an odds ratio of 2.50 (95% CI =1.98-3.14) in males. Our findings bolster the role of visceral adiposity as a potentially independent risk factor, in particular for type 2 diabetes in Caucasian females. Independent validation in other cohorts is necessary to determine whether the findings can translate to other ethnicities, or outside the UK.
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