Predisposition of the Common MC4R rs17782313 Female Carriers to Elevated Obesity and Interaction with Eating Habits

The global rise in obesity is attributed to genetic predisposition interaction with an obesogenic environment. Melanocortin 4 receptor (MC4R) rs17782313 polymorphism has been linked to common obesity with varying influence across different populations. MC4R is a crucial player in the leptin proopiomelanocortin pathway that regulates weight hemostasis. We aimed to study MC4R rs17782313 and its interaction with eating behaviors on obesity predisposition in the Israeli population. Adults’ (n = 5785, >18 y) genotype and anthropometric and demographic data were analyzed using logistic regression models adjusting for age, sex, T1DM, and T2DM. MC4R rs17782313 significantly predisposes to elevated obesity risk under the recessive and additive models (OR = 1.38, 95% CI: 1.1–1.72, p = 0.005 and OR = 1.1, 95% CI: 1.01–1.2, p = 0.03, respectively) adjusted for confounders (age, sex, T1DM, and T2DM). Stratification by sex demonstrated that carrying the common MC4R rs17782313 is significantly associated with an elevated predisposition to obesity under the recessive model among females only (OR = 1.41, 95% CI: 1.09–1.82, p = 0.01), with an average of 0.85 BMI increment compared with wild type and one risk allele carriers. MC4R rs17782313 significantly interacted with several eating behaviors to enhance the risk of obesity. Our findings demonstrate that MC4R rs17782313 homozygous female carriers are significantly predisposed to obesity amplified by eating behaviors.