Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes

Aims/hypothesis Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. Methods The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m 2 and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p<0.05) with case–control status, from four selected annotation categories or from