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Objective:Birth weight reflects prenatal metabolic adaption and has been related to later-life obesity risk. This study aimed to evaluate whether birth weight modifies the effect of genetic susceptibility on obesity risk in young Chinese.Methods:We recruited 540 young (14-30 years) and obese patients (body mass index, BMI30 kg m−2), and 500 age- and sex-matched normal-weight healthy individuals (BMI<23 kg m−2). We genotyped 23 BMI-associated genetic variants identified from recent genome-wide association studies (GWAS) in Caucasians with European ancestry with minor allele frequency>0.05 in HapMap Han Chinese in Beijing, China.Results:Six loci, including SEC16B, GNPDA2, BDNF, FTO, MC4R and TMEM160, were significantly associated with obesity risk, with odds ratio from 1.314 to 1.701. The 23 risk loci accounted for 6.38% of the genetic variance in obesity. We created two genetic risk scores (GRSs) by summing the risk alleles of all 23 (GRS1) and 6 obesity-associated (GRS2) genetic variants. Prediction of obesity was significantly improved (P<0.001) when the GRS1 and GRS2 were added to a model with age and gender, with improvement of discrimination for obesity by 0.8% and 2.7%, respectively. In addition, we found that the two GRSs interacted with birth weight in relation to obesity (Pinteraction<0.001). The genetic effect appeared to be more pronounced in individuals with normal range of birth weight (25-75%) than those with either low (<25%) or high (>75%) birth weight.Conclusion:We confirmed the associations of the single-nucleotide polymorphism tagging six loci reported in recent GWAS with obesity in young Chinese. Our data also suggest birth weight may significantly modify genetic susceptibility to obesity risk. [ABSTRACT FROM AUTHOR]