Genome-Wide and Abdominal Imaging Data Characterizes Common Alleles Associated with Higher BMI and Subcutaneous Fat but Less Liver Fat and Lower Risk of Type 2 Diabetes

Genetic studies have identified “favourable adiposity” variants - where the allele associated with higher adiposity is associated with lower risk of type 2 diabetes. We took a novel approach to find more of these alleles and find the underlying mechanisms. We first performed a genome wide association study (GWAS) of body fat percentage using 451000 individuals from UK Biobank. Second, we used published genetic data in a multivariate test to find alleles associated with higher adiposity but a “favourable” metabolic phenotype: higher HDL-C, adiponectin, sex hormone binding globulin, but lower triglycerides, fasting insulin and alanine transaminase. Third, we used abdominal imaging data from 4 studies to define the adiposity phenotype in more detail. We identified 620 variants associated with body fat percentage (p “Favourable adiposity” alleles associated with higher BMI but lower risk of type 2 diabetes are characterized by higher subcutaneous but lower liver fat. Disclosure H. Yaghootkar: None. Y. Ji: None. A.M. Yiorkas: None. F. Frau: None. D. Mook-Kanamori: None. R. de Mutsert: None. J. Tyrrell: None. S.E. Jones: None. R. Beaumont: None. A.R. Wood: None. L. Thomas: None. K.V. Allebrandt: None. N. Stefan: Consultant; Self; Merck Sharp & Dohme Corp.. Speaker9s Bureau; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca. Speaker9s Bureau; Self; AstraZeneca, OmniaMed Ltd.. H. Staiger: None. E. Pearson: Speaker9s Bureau; Self; Eli Lilly and Company. A.I. Blakemore: None. J.D. Bell: None. T.M. Frayling: None.