rs8050136

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.

This cross-sectional study of 792 Latin American subjects examined associations between FTO and IRX3 gene variants with obesity and metabolic disorders. While FTO and IRX3 SNPs were not in linkage disequilibrium, the TT genotype of rs9939609 (FTO) was associated with increased waist circumference (adj-p=0.01), and rs3751723 (IRX3) was associated with body weight excess (OR=1.06, adj-p=0.03). A FTO-IRX3 haplotype (G-A-A-T) was also associated with body weight excess (OR=0.67, p=0.04), suggesting gene-gene interaction effects independent of genetic ancestry.

This study demonstrates a significant gene-gene interaction between the obesity-risk FTO rs8050136 polymorphism and the dopamine D2 receptor ANKK1/TaqIA rs1800497 polymorphism affecting body composition and insulin sensitivity. Among 2245 participants from the Tübingen Family study and 2921 from the Malmö Diet and Cancer study, the FTO variant was associated with increased body fat (β 0.056±0.016) and waist circumference (β 0.017±0.008) and reduced insulin sensitivity (β -0.121±0.037) only in carriers of the ANKK1 T risk allele; no associations were found in ANKK1 C allele homozygotes. Brain fMRI imaging in 45 participants also showed the interaction on central insulin sensitivity in the caudate nucleus.

This doctoral thesis examines the role of physical activity, physical fitness, and exercise on immunometabolism during pregnancy across six studies in overweight/obese pregnant women. In the genetic analysis (n=81), neonatal birth weight was significantly greater in mothers carrying the CC genotype at rs6567160 and rs17782313 in the MC4R gene, though gestational weight gain was not influenced by maternal FTO or MC4R genotypes.

This two-stage association study followed up an obesity-related SNP in SYPL2 to reveal novel associations with hip circumference (HC). In a combined cohort of 3,693 individuals, rs9661614 (T>C) was significantly associated with HC in women (FDR-corrected p=1.7×10⁻²), with heterozygotes showing ~1.3-1.4 cm narrower hips compared to homozygotes. A second SNP, rs485660 (G>A), showed weaker evidence (FDR p=0.2 in women). The associations were sex-specific, present in women but absent in men, suggesting SYPL2 preferentially affects gynoid fat distribution.

Study examined association between FTO (obesity-related gene) and ADHD using family-based association tests. Found statistically significant association between rs8050136 (risk allele A) and ADHD traits, with stronger associations in children not exposed to maternal smoking during pregnancy. Suggests FTO may help explain the complex link between obesity and ADHD.

This systematic study screened 18 T2D-associated SNPs and 5 environmental factors (trans-β-carotene, cis-β-carotene, γ-tocopherol, heptachlor epoxide, PCB170) for gene-environment interactions using NHANES data (1999-2000, 2001-2002). The strongest interaction was between rs13266634 (SLC30A8) and trans-β-carotene: in subjects with low trans-β-carotene levels, the per-risk-allele OR was 1.8 (95% CI 1.3-2.6), 40% higher than the marginal effect, and this interaction withstood Bonferroni correction (p = 0.006, FDR 1.5%). Four interactions total achieved FDR < 20%, suggesting that nutrient levels modify genetic risk for T2D.

Case-control study of 673 preterm birth (PTB) cases vs 1,119 controls across four maternal cohorts testing 35 SNPs in cardiovascular, inflammatory, and metabolic disease genes. Found 13 statistically significant associations with PTB (P<0.05), more than expected by chance (binomial P=0.02). Most significant was HLA-DQA1 rs9272346 G allele protective effect in US White mothers (P=0.02, OR=0.65, 95% CI 0.46-0.94), which nominally replicated in Danish cohort (P=0.02, OR=0.85, 95% CI 0.75-0.97) but lost significance after correction for multiple testing.

This comprehensive review examines the association between type 2 diabetes mellitus (T2DM) and multiple myeloma (MM) risk. Genetic variants linked to T2DM show opposite associations with MM compared to diabetes GWAS: variants like CDKN2A-2B rs2383208, IGF1 rs35767, KCNQ1 rs2237892, and MADD rs7944584 increase MM risk, while FTO rs8050136, KCNJ11 rs5215/rs5219, LTA rs1041981, and THADA rs7578597 decrease risk. The IGF1 rs35767 promoter polymorphism is strongly associated with MM risk via cell proliferation mechanisms. A meta-analysis of 20 observational studies (>3 million participants) found T2DM patients had OR=1.53 (95% CI, 1.30-1.81) for MM, and MetS patients had OR=1.39 (95% CI, 1.17-1.64), mediated through insulin resistance, hyperinsulinemia, inflammatory cytokines (IL-6, TNF-α, IL-1β), dyslipidemia, and acidosis pathways.

This case-control study of 2,033 colorectal cancer cases and 9,640 controls investigated whether BMI and waist size susceptibility variants are associated with colorectal cancer risk. Two obesity SNPs showed significant associations: KCTD15 rs29941 (OR = 0.90, p = 0.01) was protective, while MC4R rs17782313 (OR = 1.12, p = 0.02) increased risk. However, neither association remained significant after multiple comparisons correction, and overall obesity variants showed minimal effects on colorectal cancer.

This case-control study investigated 25 T2DM-associated SNPs in a multi-ethnic Hawaiian cohort (291 GDM cases, 734 controls) and found ethnicity-specific associations with gestational diabetes. Key findings in Filipinos included rs1113132 (EXT2, OR=1.52, p=0.028), rs1111875 (HHEX, OR=1.5, p=0.047), rs2237892 (KCNQ1, OR=0.49, p<0.001), rs10830963 (MTNR1B, OR=0.63, p=0.025), and rs13266634 (SLC30A8, OR=0.58, p=0.011). In Japanese women, rs4402960 (IGFBP2, OR=0.5, p=0.031) and rs2237892 (KCNQ1, OR=0.5, p=0.03) were significant. Pacific Islanders showed associations with rs10830963 (MTNR1B, OR=0.52, p=0.037) and rs13266634 (SLC30A8, OR=2.43, p=0.03). No SNPs showed consistent associations across all three ethnic groups.

This association study of 4,213 Danish individuals examined 25 type 2 diabetes risk variants and their association with birthweight. The study found that type 2 diabetes risk alleles near ADCY5 (rs11708067, β = -33 g, p = 0.004), CDKAL1 (rs7756992, β = -22 g, p = 0.04), and HHEX-IDE (rs1111875, β = -16 g in meta-analysis, p = 8×10⁻⁵, n = 25,164) were associated with reduced birthweight, supporting the fetal insulin hypothesis. Meta-analyses confirmed these associations and showed no strong general effect on birthweight from the 25 common type 2 diabetes risk alleles combined.

This case-control study in 869 Korean women with gestational diabetes mellitus (GDM) and 632 non-diabetic controls examined whether type 2 diabetes-associated genetic variants discovered in recent GWAS are also associated with GDM. Multiple variants showed significant associations with GDM, including rs7756992 and rs7754840 in CDKAL1 (OR 1.55, p=4.17×10⁻⁹), rs10811661 in CDKN2A-CDKN2B (OR 1.49, p=1.05×10⁻⁷), variants in HHEX, rs4402960 in IGF2BP2 (OR 1.18, p=0.03), rs13266634 in SLC30A8 (OR 1.24, p=0.005), and rs7903146 in TCF7L2 (OR 1.58, p=0.038).

Analysis of 27 FTO gene variants in 1,424 Hispanic Americans and 604 African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS) found multiple SNPs associated with BMI, waist circumference, and subcutaneous adipose tissue (p-values 0.001-0.05 in Hispanics), confirming FTO's role in overall fat mass rather than visceral fat distribution. Key variants rs9939609, rs8050136, rs1121980, rs1421085, rs17817449, and rs3751812 showed consistent associations with adiposity measures, with effect sizes of 0.3-2.4 kg/m² per allele for BMI in Hispanic Americans.

This study examined 704 Old Order Amish individuals and identified 26 FTO gene variants associated with BMI (P=.04 to <.001), with rs1861868 (0.75 BMI increase per A allele, P<.001) and rs1477196 (0.84 BMI increase per C allele, P<.001) showing the strongest associations. Notably, the study found a significant gene-by-environment interaction where increased physical activity substantially blunted the effects of FTO variants on body weight, suggesting that genetic predisposition to obesity can be mitigated through adequate physical activity.

In 55 Europid participants, FTO mRNA expression in adipose tissue was 3-fold higher in subcutaneous versus visceral depots and showed significant negative correlations with BMI and body fat percentage. However, the obesity-associated SNP rs8050136 (in linkage disequilibrium with rs9939609) was not associated with FTO or RPGRIP1L mRNA expression levels in either adipose tissue depot.

This comprehensive review article traces the evolution of pharmacogenetics from single-gene analysis to whole-genome approaches. It discusses validated pharmacogenetic biomarkers with clinical impact including CYP2D6, CYP2C9, CYP2C19, TPMT, DPD, VKORC1, UGT1A1, and ADRB1/ADRB2, providing examples of how genetic variants affect drug metabolism and response. The paper emphasizes the importance of integrating pharmacogenetic information into clinical practice and drug development.

This case-control association study in 864 Japanese type 2 diabetes patients and 864 controls confirmed that three SNPs in HHEX (rs5015480 OR=1.46, rs7923837 OR=1.40, rs1111875 OR=1.30) were significantly associated with type 2 diabetes across ethnic groups. SNPs in FTO, CDKAL1, CDKN2B, and SLC30A8 showed nominal associations, while several SNPs were associated with impaired pancreatic beta cell function measured by HOMA-beta index.