Association study uncovers obesity-linked variants in mobile elements as potential regulators of gene expression

Obesity results from excessive fat accumulation driven by both genetic and environmental influences. While genome-wide association studies have found over 1,000 obesity-related variants, most research has centered on individuals of European descent. This study conducted a candidate gene association meta-analysis in 3,866 unrelated Mexican participants, examining 356 genes linked to obesity, abdominal obesity, body mass index, and waist circumference. The analysis replicated 56 known single-nucleotide variant associations and identified previously unreported association signals in genes such as CNTN5, EML6, KCNMB2, LHFPL3, and FTO. Functional in silico annotation revealed that variants, both within and outside mobile genetic elements, act as expression quantitative trait loci for 116 genes, especially in nervous, digestive, and endocrine tissues. These findings confirm established loci's relevance in Mexicans and highlight potentially population-specific candidate variants, emphasizing the importance of including diverse and underrepresented populations in genetic research on obesity.