rs10938397

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

In a population-based cohort of 3,179 children, the study tested two weighted genetic risk scores based on 15 childhood and 97 adult BMI-associated SNPs, plus ten individual appetite/satiety SNPs, for association with eating behavior measures. The 97 SNP adult BMI risk score was nominally associated with lower satiety responsiveness (β: -0.007 SD, 95% CI -0.013, 0.000), while individual SNPs rs11030104 (BDNF) and rs10733682 (LMX1B) showed nominal associations with reduced satiety responsiveness (β: -0.057 to -0.087 SD). Overall, findings do not strongly support that BMI-associated SNPs influence eating behavior at this young age.

Association study of 35 GWAS-identified body mass SNPs in 949 elderly Swedish participants (mean age 70-75 years). Significant association found between rs10968576 (LINGO2, intron 4) and BMI with a larger effect size (β = 0.69 kg/m²) than reported in younger populations, suggesting age-specific genetic effects on body mass in the elderly.

This literature review examines the influence of genetic polymorphisms on obesity development and adaptive responses to physical activity, focusing on five candidate genes: COMT (rs4680, Val158Met), DRD2 (rs1800497 Taq1A and rs1799732), FABP2 (rs1799883, Ala54Thr), FTO (rs9939609, A/T), and UCP1 (rs1800592, A-3826G). The review synthesizes molecular mechanisms, phenotypic associations, and implications for human health and training adaptations, noting that physical activity reduces the FTO genetic effect on obesity risk by 30-80% and that various polymorphisms show differential impacts on body composition and metabolic responses to exercise.

This study examined whether 32 obesity-associated genetic risk alleles are associated with childhood ADHD in a German GWAS sample (495 cases, 1,300 controls) and a meta-analysis (2,064 trios, 896 cases, 2,455 controls). The obesity risk allele G at rs206936 in NUDT3 was associated with increased ADHD risk (OR=1.39, P=3.4×10⁻⁴), and rs6497416 in GPRC5B showed association with ADHD in the meta-analysis (P=7.2×10⁻⁴). Several obesity-related SNPs were associated with ADHD endophenotypes including inattention and hyperactivity/impulsivity.

Genome-wide association study examining common variants near BDNF (rs6265, rs925946) and SH2B1 (rs7498665) in relation to snacking behavior across three European cohorts (French obese children, Swiss obese, D.E.S.I.R.). The study reports nominal evidence of association, with rs925946 in BDNF showing OR=1.21 (p=5.03×10⁻³) in the D.E.S.I.R. cohort and rs7498665 in SH2B1 showing OR=1.17 (p=9.57×10⁻³) in the Swiss cohort.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Replication study of 14 obesity-associated SNPs from 13 loci in 18,264 Japanese participants, confirming associations at 11 loci including TMEM18 (rs4854344, p=7.1×10⁻⁷ for BMI), FTO, MC4R, BDNF, and others. Six obesity variants also associated with type 2 diabetes after BMI adjustment (OR 1.05-1.17), with FTO showing strong meta-analyzed association in East Asians (OR 1.13, p=7.8×10⁻¹⁰).

This study tests the thrifty genotype hypothesis by examining 17 confirmed type 2 diabetes susceptibility loci and 13 obesity-susceptibility loci for signatures of positive selection. Using ancestral/derived allele analysis, integrated haplotype scores (iHS), and population differentiation (FST), the authors found limited evidence supporting the thrifty genotype hypothesis. Only rs7901695 at TCF7L2 showed notably elevated FST values (0.579 between JPT+CHB and YRI populations), and FTO showed the strongest selection signal among obesity loci (iHS=1.991).