Genetic susceptibility, birth weight and obesity risk in young chinese
J. Shi1, J. Hong1, L. Qi3, B. Cui2, W. Gu1, Y. Zhang1, L. Li1, M. Xu1, L. Wang1, Y. Zhai1, L. Miao1, R. Wang1, Y. Bi1, W. Wang1 & G. Ning1
Thus far, approximately 30 loci influencing body mass index (BMI) and the risk of obesity have been identified. In this study, we aimed to examine the individual and joint associations of 23 BMI-associated loci identified from recent genome-wide association studies in Caucasians with obesity risk in young Chinese. Birth weight reflects prenatal metabolic adaption and has been related to later-life obesity risk. We particularly assessed whether these genetic variants interacted with birth weight in relation to obesity risk. We recruited 540 young (1430 years) and obese patients (BMI ≥ 30 kg/m2), and 500 age- and sex-matched normal-weight healthy individuals (BMI < 23 kg/m2).We genotyped genetic variants in those 23 BMI-associated loci. 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. These risk loci accounted for 4.84% of the genetic variance in obesity. We created a genetic risk score (GRS) by summing the risk alleles of these associated genetic variants. Prediction of obesity was significantly improved (P< 0.001) when the GRS was added to a model with age and gender, with improvement of discrimination for obesity by 2.7%. In addition, we found that the GRS interacted with birth weight in relation to obesity (P interaction< 0.001). The genetic effect appeared to be more pronounced in individuals with normal range of birth weight (2575%) than those with either low (<25%) or high (>75%) birth weight. In conclusion, we showed that the combined genetic risk of variants identified from European populations might significantly improve the identification of high-risk group of obesity in young Chinese. For the first time, we demonstrated birth weight might interact with genetic susceptibility in relation to obesity risk in later life, which deserves consideration in future efforts to prevent obesity.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.