Discoveries from genome-wide association studies (GWAS) of metabolic phenotypes such as type 2 diabetes and obesity only explain less than ~10% of the heritability. However, we have recently shown that studying the historically small and isolated Greenlandic population constitutes a unique and very valuable alternative design, which offers increased statistical power and potential to disclose underlying biological mechanisms. In this context, we search for variation associated with cardiometabolic traits in the Greenlandic Inuit population with a focus on variants which are predicted to cause loss of protein function. We are mapping the loss of function variants through genome sequencing of the Greenlandic genome focusing on variants which segregate at higher frequency in the Greenlandic population than in the main populations.