Variants in common diseases

Abstract

Most common diseases arise from interaction between multiple genetic variations and factors such as diet. Studies of such diseases that exploit the rich data on variation in the human genome are just beginning. Overeating and physical inactivity are major causes of type 2 diabetes mellitus, but they affect only genetically susceptible individuals and the genetic basis of the disease is notoriously complex. Recent research has suggested that specific genes may be associated with the risk of developing the disease, however. Now a genome-wide search using high-density genotyping arrays has identified four previously unknown genes as diabetes risk factors, and confirmed a known association with the TCF7L2 gene. Together these five genes may contribute a sizeable fraction of the disease risk in type 2 diabetes, and analysis of their function should clarify the pathogenesis of diabetes and point to new drug targets. In addition, individuals shown to have these mutations could minimize their risk by adjusting diet.