The role of polygenic susceptibility to obesity among carriers of pathogenic mutations in MC4R in the UK Biobank population.

ABSTRACT:

Background

Melanocortin 4 receptor (MC4R) deficiency, caused by mutations in MC4R, is the most common cause of monogenic forms of obesity. However, these mutations have often been identified in small-scale, case-focused studies. Here, we assess the penetrance of previously reported MC4R mutations at a population level. Furthermore, we examine why some carriers of pathogenic mutations remain of normal weight, to gain insight into the mechanisms that control body weight.

Methods and findings

We identified 59 known obesity-increasing mutations in MC4R from the Human Gene Mutation Database (HGMD) and Clinvar. We assessed their penetrance and effect on obesity (body mass index [BMI] ≥ 30 kg/m2) in >450,000 individuals (age 40-69 years) of the UK Biobank, a population-based cohort

SUBMITTER: Chami N 

PROVIDER: S-EPMC7373259 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature