Repeat length variations in polyglutamine disease-associated genes affect body mass index.


Department of Neurology, Leiden University Medical Centre, 2300 RC, Leiden, The Netherlands. [Email]


The worldwide prevalence of obesity, a major risk factor for numerous debilitating chronic disorders, is increasing rapidly. Although a substantial amount of the variation in body mass index (BMI) is estimated to be heritable, the largest meta-analysis of genome-wide association studies (GWAS) to date explained only ~2.7% of the variation. To tackle this 'missing heritability' problem of obesity, here we focused on the contribution of DNA repeat length polymorphisms which are not detectable by GWAS.