Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, The Netherlands.
Eur J Epidemiol. 2011 Jun;26(6):463-73. doi: 10.1007/s10654-011-9583-4. Epub 2011 May 5.
Recent genome-wide association (GWA) studies identified several common variants for obesity: rs9939609 in FTO, rs7566605 near INSIG2 and both rs17782313 and rs17700633 near the MC4R gene. This study aimed to assess the influence of these polymorphisms on development of adiposity in European- (EA) and African-American (AA) youth in two ongoing longitudinal studies including 986 and 606 participants with age ranges of 10-25.8 and 4.0-23.9 years, respectively. Individual growth curve modeling was conducted separately in the two studies. We tested the effect of the SNPs on levels and increase with age (i.e., slope) of weight, body mass index (BMI), waist circumference and skinfolds from childhood to adulthood, and potential moderation by ethnicity or gender. Beta coefficients computed in the two studies were pooled using meta-analysis. Rs9939609 was associated with logtransformed levels of BMI (β = 0.021, P = 0.01), weight (β = 0.019, P = 0.04) and waist circumference (β = 0.012, P = 0.04). Rs17782313 was associated with triceps (β = 0.05, P = 0.02). Significant interactions of rs17700633 with gender were observed on subscapular-, suprailiac- and sum of skinfolds, with significant associations limited to males (P < 0.05). No significant interactions with ethnicity were found. Only one effect on the slope was observed, rs17700633 showed a significant interaction with age on triceps (β = 0.004, P = 0.04). In two longitudinal studies of EA and AA youth, we replicated the effect of FTO and common variants near MC4R on general and central adiposity. These variants did not affect the increase with age of adiposity from childhood to adulthood with one exception. Common variants for obesity identified in GWA studies have detectable but modest effects on growth curves for adiposity in EA and AA youth.
最近的全基因组关联（GWA）研究鉴定出了几个与肥胖相关的常见变异：FTO 基因中的 rs9939609、INSIG2 附近的 rs7566605 以及 MC4R 基因附近的 rs17782313 和 rs17700633。本研究旨在评估这些多态性对两项正在进行的纵向研究中欧洲裔（EA）和非裔美国人（AA）青少年肥胖发展的影响，这两项研究共纳入了 986 名和 606 名年龄分别为 10-25.8 岁和 4.0-23.9 岁的参与者。个体生长曲线模型分别在这两项研究中进行。我们测试了 SNP 对体重、体重指数（BMI）、腰围和皮褶厚度从儿童到成年的水平和随年龄增长的变化（即斜率）的影响，以及对种族或性别潜在的调节作用。meta 分析合并了两项研究中计算出的β系数。rs9939609 与 BMI（β=0.021，P=0.01）、体重（β=0.019，P=0.04）和腰围（β=0.012，P=0.04）的对数转换水平相关。rs17782313 与三头肌（β=0.05，P=0.02）相关。rs17700633 与性别存在显著的交互作用，表现在肩胛下、髂嵴上和皮褶总和，仅男性存在显著相关性（P<0.05）。未发现与种族的显著相互作用。仅观察到一个斜率的影响，rs17700633 与三头肌的年龄存在显著交互作用（β=0.004，P=0.04）。在对 EA 和 AA 青少年进行的两项纵向研究中，我们复制了 FTO 和 MC4R 附近常见变异对一般和中心性肥胖的影响。这些变异并没有影响从儿童到成年的肥胖随年龄增长的变化，只有一个例外。GWA 研究中鉴定出的肥胖常见变异对 EA 和 AA 青少年的肥胖生长曲线有可检测但适度的影响。
