Benjamin Ashlee M, Suchindran Sunil, Pearce Kaela, Rowell Jennifer, Lien Lillian F, Guyton John R, McCarthy Jeanette J
Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
J Obes. 2011;2011:329038. doi: 10.1155/2011/329038. Epub 2010 Dec 26.
Obesity is an increasingly prevalent and severe health concern with a substantial heritable component and marked sex differences. We sought to determine if the effect of genetic variants also differed by sex by performing a genome-wide association study modeling the effect of genotype-by-sex interaction on obesity phenotypes. Genotype data from individuals in the Framingham Heart Study Offspring cohort were analyzed across five exams. Although no variants showed genome-wide significant gene-by-sex interaction in any individual exam, four polymorphisms displayed a consistent BMI association (P-values .00186 to .00010) across all five exams. These variants were clustered downstream of LYPLAL1, which encodes a lipase/esterase expressed in adipose tissue, a locus previously identified as having sex-specific effects on central obesity. Primary effects in males were in the opposite direction from females and were replicated in Framingham Generation 3. Our data support a sex-influenced association between genetic variation at the LYPLAL1 locus and obesity-related traits.
肥胖是一个日益普遍且严重的健康问题，具有显著的遗传成分和明显的性别差异。我们试图通过进行一项全基因组关联研究来确定基因变异的影响是否也因性别而异，该研究对基因型与性别的相互作用对肥胖表型的影响进行建模。对弗雷明汉心脏研究后代队列中个体的基因型数据进行了五次检查的分析。尽管在任何一次单独检查中没有变异显示出全基因组显著的基因与性别的相互作用，但有四个多态性在所有五次检查中都显示出一致的体重指数关联（P值为0.00186至0.00010）。这些变异聚集在LYPLAL1的下游，LYPLAL1编码一种在脂肪组织中表达的脂肪酶/酯酶，该位点先前被确定对中心性肥胖有性别特异性影响。男性的主要影响方向与女性相反，并在弗雷明汉第三代中得到了重复验证。我们的数据支持LYPLAL1基因座的遗传变异与肥胖相关性状之间存在性别影响的关联。
