rs1558902

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.

This genome-wide association study (GWAS) of radiographic tibiofemoral knee osteoarthritis in 3,898 cases and 3,168 controls from four North American cohorts identified one novel locus near LSP1P3 (rs4867568, OR=0.84, P=3.02×10⁻⁶) and confirmed associations with previously reported loci GDF5 (rs143383, OR=1.12, P=2.13×10⁻³) and FTO (rs8044769, OR=1.10, P=6.13×10⁻³). Despite the large sample size and standardized radiographic phenotyping, no variants achieved genome-wide significance, highlighting the polygenic nature of knee OA.

Mendelian Randomization study examining the causal relationship between obesity (BMI) and venous thromboembolism using 95 BMI-associated SNPs in 7,507 VTE cases and 52,632 European ancestry controls. FTO rs1558902 showed the strongest individual association with VTE (OR 1.07, P = 0.005), and genetically predicted high BMI was significantly associated with increased VTE risk (OR 1.59 per SD increase in BMI, P = 5.8 × 10^-6), providing evidence for a causal relationship between obesity and VTE.

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 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.

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 meta-analysis of eight PCOS cohorts (2,548 women) found that FTO rs9939609 and rs1421085 polymorphisms have significantly greater effects on BMI and body weight in PCOS patients than in the general population. Each additional effect allele increased BMI by 0.19 z-score units (p=2.26×10⁻¹¹) and body weight by 0.20 z-score units (p=1.02×10⁻¹⁰), demonstrating effects more than two times greater than previously reported.

Transethnic genome-wide meta-analysis in 159,940 individuals identified 60 common genetic variants associated with HbA1c levels. Variants were classified as glycemic (19), erythrocytic (22), or unclassified (19) based on their biological mechanisms. Glycemic variants were associated with higher type 2 diabetes risk (OR=1.05 per allele, p=3×10⁻²⁹), while erythrocytic variants were not. The X-linked G6PD G202A variant showed a large effect in African Americans (0.81% HbA1c reduction per allele) but minimal effects in other ancestries, potentially causing 2% of African American T2D cases to remain undiagnosed when using HbA1c screening.