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

Area of Science:

• Genetics
• Obesity Research
• Population Genetics

Background:

• Obesity is a complex trait influenced by genetic and environmental factors.
• Genome-wide association studies (GWAS) have identified over 1,000 obesity-related genetic variants.
• Most genetic research on obesity has focused on European populations, limiting generalizability.

Purpose of the Study:

• To conduct a candidate gene association meta-analysis in a Mexican population.
• To examine genetic variants associated with obesity, abdominal obesity, body mass index (BMI), and waist circumference.
• To identify novel obesity-related genetic associations in an underrepresented population.

Main Methods:

• A meta-analysis of candidate gene associations was performed.
• 3,866 unrelated Mexican participants were analyzed.
• 356 obesity-related genes and their single-nucleotide variants (SNVs) were examined.

Main Results:

• 56 known SNV associations with obesity-related traits were replicated.
• Novel association signals were identified in genes including CNTN5, EML6, KCNMB2, LHFPL3, and FTO.
• Functional annotation indicated that variants act as expression quantitative trait loci (eQTLs) for 116 genes, particularly in nervous, digestive, and endocrine tissues.

Conclusions:

• Established obesity-related genetic loci are relevant in the Mexican population.
• Potentially population-specific candidate variants were discovered.
• The study underscores the importance of including diverse populations in genetic research to understand obesity etiology comprehensively.