Genetic susceptibility, birth weight and obesity risk in young Chinese.
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.


CONCLUSIONS
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.
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Endocrine and Metabolic E-Institutes of Shanghai Universities (EISU) and Key Laboratory for Endocrinology and Metabolism of Chinese Health Ministry, Rui-jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
J
J
Hong
J
J
Shi
L
L
Qi
B
B
Cui
W
W
Gu
Y
Y
Zhang
L
L
Li
M
M
Xu
L
L
Wang
Y
Y
Zhai
L
L
Miao
R
R
Wang
Y
Y
Bi
W
W
Wang
G
G
Ning
D000293:Adolescent; D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data*; D001724:Birth Weight; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009765:Obesity / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data*
D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; C470072:MC4R protein, human; D008565:Membrane Proteins; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; C443860:SEC16B protein, human; C579455:BDNF protein, human; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human