Hormonal
Carrying a high genetic burden of obesity-risk variants (FTO, SH2B1, MTCH2, MC4R, NEGR1, GNPDA2) causally increases total, abdominal, and gynoid adipose mass, which in turn drives a significantly higher risk of type 2 diabetes.
Your genes can make you heavier and increase your diabetes risk, but they don't dictate your fate. This study shows that genetic risk is largely mediated by body fat. While you can't change your DNA, you can manage the outcome by focusing on maintaining a healthy weight and metabolic health, as the genetic risk is not strong enough to justify ignoring lifestyle factors or relying on genetic tests for clinical decisions.
our results suggest that the weight-inducing effects of these variants are explained largely by increased adipose accumulation... The genetic burden score significantly increased diabetes risk... When all SNPs were simultaneously entered into the model... BMI explained all the predictive power attributable to the SNPs
Why this rating
Large sample size (n=4923), replication of previous GWAS, objective DEXA measurements, but observational design.
Source
Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden
Frida Renström et al. · Human Molecular Genetics · 2009
DOI 10.1093/hmg/ddp041
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