To test a gene-environment interaction model with severe obesity in determining metabolic traits, we examined the relationship between PNPLA3 I148M genotypes, serum triglycerides, insulin resistance and type 2 diabetes susceptibility in a large obese cohort, the Swedish Obese Subjects (SOS) study, before and after bariatric surgery. The gene discussed is PNPLA3; the disease is Insulin resistance.