Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies

摘要: Background: Large-scale genome-wide association studies have identified 12 genetic loci that are robustly associated with body mass index (BMI). Objectives: We examined associations and compared effect sizes of these newly obesity susceptibility various anthropometric traits assessed their cumulative effects predictive value for risk. Design: genotyped single nucleotide polymorphisms (SNPs) from each locus in 20,431 individuals (age: 39-79 y) the population-based European Prospective Investigation into Cancer Nutrition (EPIC)-Norfolk cohort. General linear model logistic regression were used to examine associations, area under receiver operating characteristic curve (AUC) was assess variants Results: Effect risk alleles ranged between 0.058 0.329 BMI (in kg/m 2 ), 0.094 0.866 kg weight, 0.085 0.819 cm waist circumference, rs1121980 (FTO locus) showing largest effect. Risk rs7132908 (FAIM2 rs17782313 (MC4R also taller height. On average, additional allele increases 0.149 (P = 1.54 x 10- 22 0.444 weight 9.88 10 -22 0.357 circumference (P= 1.10 -18 ) 10.8% (P=9.83 -16 5.5% 3.38 -10 increased risks overweight, respectively. All SNPs combined explained 0.9% variation, an AUC 0.574 (95% CI: 0.559, 0.590) prediction obesity. Conclusions: Common small on measures show different patterns traits, shown FTO locus. These effects, yet is limited.