中国汉族人群中遗传风险评分与肥胖及相关性状的关联以及身体活动的调节作用
Associations of genetic risk score with obesity and related traits and the modifying effect of physical activity in a Chinese Han population.
作者信息
Zhu Jingwen, Loos Ruth J F, Lu Ling, Zong Geng, Gan Wei, Ye Xingwang, Sun Liang, Li Huaixing, Lin Xu
机构信息
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate University of the Chinese Academy of Sciences, Shanghai, People's Republic of China.
The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, The Genetics of Obesity and Related Metabolic Traits Program, Department of Preventive Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
出版信息
PLoS One. 2014 Mar 13;9(3):e91442. doi: 10.1371/journal.pone.0091442. eCollection 2014.
BACKGROUND/OBJECTIVES: Recent large-scale genome-wide association studies have identified multiple loci robustly associated with BMI, predominantly in European ancestry (EA) populations. However, associations of these loci with obesity and related traits have not been well described in Chinese Hans. This study aimed to investigate whether BMI-associated loci are, individually and collectively, associated with adiposity-related traits and obesity in Chinese Hans and whether these associations are modified by physical activity (PA).
SUBJECTS/METHODS: We genotyped 28 BMI-associated single nucleotide polymorphisms (SNPs) in a population-based cohort including 2,894 unrelated Han Chinese. Genetic risk score (GRS), EA and East Asian ancestry (EAA) GRSs were calculated by adding BMI-increasing alleles based on all, EA and EAA identified SNPs, respectively. Interactions of GRS and PA were examined by including the interaction-term in the regression model.
RESULTS
Individually, 26 of 28 SNPs showed directionally consistent effects on BMI, and associations of four loci (TMEM18, PCSK1, BDNF and MAP2K5) reached nominal significance (P<0.05). The GRS was associated with increased BMI, trunk fat and body fat percentages; and increased risk of obesity and overweight (all P<0.05). Effect sizes (0.11 vs. 0.17 kg/m2) and explained variance (0.90% vs. 1.45%) of GRS for BMI tended to be lower in Chinese Hans than in Europeans. The EA GRS and EAA GRS were associated with 0.11 and 0.13 kg/m2 higher BMI, respectively. In addition, we found that PA attenuated the effect of the GRS on BMI (Pinteraction = 0.022).
CONCLUSIONS
Our observations suggest that the combined effect of obesity-susceptibility loci on BMI tended to be lower in Han Chinese than in EA. The overall, EA and EAA GRSs exert similar effects on adiposity traits. Genetic predisposition to increased BMI is attenuated by PA in this population of Han Chinese.
背景/目的：近期大规模全基因组关联研究已确定多个与体重指数（BMI）密切相关的基因座，主要来自欧洲血统（EA）人群。然而，这些基因座与肥胖及相关性状在中国汉族人群中的关联尚未得到充分描述。本研究旨在调查BMI相关基因座单独及共同作用时，是否与中国汉族人群的肥胖相关性状及肥胖有关，以及这些关联是否会因体力活动（PA）而改变。
对象/方法：我们对一个包含2894名无血缘关系的汉族人群的队列进行了28个与BMI相关的单核苷酸多态性（SNP）基因分型。基于所有、EA和东亚血统（EAA）鉴定出的SNP，分别通过累加增加BMI的等位基因来计算遗传风险评分（GRS）、EA遗传风险评分和EAA遗传风险评分。通过在回归模型中纳入交互项来检验GRS与PA的相互作用。
结果
单独来看，28个SNP中有26个对BMI显示出方向一致的影响，4个基因座（TMEM18、PCSK1、BDNF和MAP2K5）的关联达到名义显著性（P<0.05）。GRS与BMI升高、躯干脂肪和体脂百分比增加相关；且肥胖和超重风险增加（所有P<0.05）。中国汉族人群中GRS对BMI的效应大小（0.11 vs. 0.17 kg/m²）和解释方差（0.90% vs. 1.45%）往往低于欧洲人。EA遗传风险评分和EAA遗传风险评分分别与BMI升高0.11和0.13 kg/m²相关。此外，我们发现PA减弱了GRS对BMI的影响（P交互作用=0.022）。
结论
我们的观察结果表明，肥胖易感基因座对BMI的综合影响在中国汉族人群中往往低于EA人群。总体、EA和EAA遗传风险评分对肥胖性状的影响相似。在这个中国汉族人群中，PA减弱了BMI升高的遗传易感性。
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