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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity.
Using exome-sequencing in , individuals including , non-Europeans from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance.
We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. The ability to store excess calories in adipose tissue in the form of triglycerides is essential to metabolic health in humans 1 , 2 , 3 , 4 , 5 , 6 and the distribution of fat in the body is a major risk factor for cardiometabolic disease 6 , 7 , 8 , 9 , independent of overall adiposity.
In individuals from different world regions, a higher waist-to-hip circumference ratio WHR , a simple proxy-measure of the relative abundance of abdominal to gluteofemoral fat, is strongly associated with higher incidence of cardiovascular disease and diabetes 7 , 8 , 10 , independent of body mass index BMI. While fat distribution is a major epidemiological risk factor accounting for a large share of the global morbidity of cardiometabolic disease, there is a lack of therapeutic options to modify improper fat storage.
