ArticleGenetics and molecular biology2026
Influence of reward-related genetic variants on BMI and predisposition to obesity: Systematic review and meta-analysis.
Article in Genetics and molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Obesity results from a chronic imbalance between caloric intake and energy expenditure, leading to the accumulation of excess body fat. This imbalance is influenced by endocrine, molecular, genetic, demographic, environmental, and lifestyle factors, with the brain reward cascade emerging as a key overlapping pathway. This study hypothesizes that cascade dysregulation leads to reward deficiency, causing stronger cravings and overeating. This study investigates the contribution of genetic variants in the brain reward cascade to body mass index (BMI), overweight, and obesity. A systematic search was conducted across five databases. Eligible studies evaluated associations between variants in reward-related genes (COMT, DRD2, DRD4, MAO-A, SLC6A3, SLC6A4) and BMI or obesity. In total, 117 studies were included in the systematic review, and 31 provided sufficient data for meta-analysis. Eighteen variants showed significant associations with BMI, with the strongest evidence observed for the Val158Met (COMT), Taq1A (DRD2), 48 bp VNTR (DRD4), 40 bp VNTR (SLC6A3) and 5-HTTLPR (SLC6A4). Meta-analyses of Taq1A showed a significant association of the A1 allele with obesity. This study highlights consistent associations between genetic variants in the reward cascade and susceptibility to weight gain, providing a foundation for more precise prevention and personalized obesity management.
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