Genetics of Obesity

Abstract

Obesity is a major health problem that has reached epidemic levels worldwide. Obesity is considered a highly heritable and genetically heterogeneous disorder. Despite the improvement in our understanding of the genetic basis of obesity, the underlying genetic cause of most families with extreme obesity is still unknown. In this study, we aim to elucidate the missing heritability of obesity in bariatric surgery patients with familial history of obesity. About 100 probands from France, the UK and Qatar will be screened for known obesity variants in MC4R (and LEP if belong to consanguineous family) by Sanger sequencing and for two obesity-causing microdeletions at chr16p11.2 by MLPA. The families of ten of these probands not showing known monogenic obesity variants will be further analysed to seek new rare obesity-causing variants by whole exome sequencing and Illumina genotyping. We will examine the effect of the identified variants at the gene expression level by performing expression profiling analysis in blood and insulin-responsive tissues (muscle, liver, subcutaneous and visceral fat) from the probands and in blood for the other family members. Moreover, we will investigate the effect of the variants on obesity surgery outcomes such as weight loss and reoperation rates. Bariatric surgery offers a valuable opportunity to collect tissues from obese patients that can allow the integration of genetic information with gene expression to investigate the genetic basis of obesity. This research will provide novel insight into better health care protocols such as personalised medicine and genetic counselling for obesity, and could lead to the development of better treatment options for the future.