Cilius E. Fonvig

Abstract Obesity is a heterogeneous condition not adequately captured by a single adiposity trait. We conducted a multi-trait genome-wide association analysis using individual-level data from 452,768 UK Biobank participants to study obesity in relation to cardiometabolic health. We defined continuous ‘uncoupling phenotypes’, ranging from high adiposity with healthy cardiometabolic profiles to low adiposity with unhealthy ones.

4 DISCUSSION The present study investigated the associations between genetic susceptibility for liver fat accumulation and liver and cardiometabolic risk outcomes in a well-characterized paediatric population. The GRS, which was based on eight genome-wide significant steatogenic variants, was robustly associated with higher liver fat content, plasma concentrations of liver enzymes, and with decreased circulating lipid levels in childhood.