Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Rd, Zhunan, Miaoli 350, Taiwan, ROC.
Hum Genet. 2010 Nov;128(5):501-13. doi: 10.1007/s00439-010-0877-5. Epub 2010 Aug 20.
To dissect the genetic architecture of sexual dimorphism in obesity-related traits, we evaluated the sex-genotype interaction, sex-specific heritability and genome-wide linkages for seven measurements related to obesity. A total of 1,365 non-diabetic Chinese subjects from the family study of the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance were used to search for quantitative trait loci (QTLs) responsible for the obesity-related traits. Pleiotropy and co-incidence effects from the QTLs were also examined using the bivariate linkage approach. We found that sex-specific differences in heritability and the genotype-sex interaction effects were substantially significant for most of these traits. Several QTLs with strong linkage evidence were identified after incorporating genotype by sex (G × S) interactions into the linkage mapping, including one QTL for hip circumference [maximum LOD score (MLS) = 4.22, empirical p = 0.000033] and two QTLs: for BMI on chromosome 12q with MLS 3.37 (empirical p = 0.0043) and 3.10 (empirical p = 0.0054). Sex-specific analyses demonstrated that these linkage signals all resulted from females rather than males. Most of these QTLs for obesity-related traits replicated the findings in other ethnic groups. Bivariate linkage analyses showed several obesity traits were influenced by a common set of QTLs. All regions with linkage signals were observed in one gender, but not in the whole sample, suggesting the genetic architecture of obesity-related traits does differ by gender. These findings are useful for further identification of the liability genes for these phenotypes through candidate genes or genome-wide association analysis.
为了剖析肥胖相关特征的性别二态性的遗传结构，我们评估了七个肥胖相关特征的性别-基因型相互作用、性别特异性遗传力和全基因组连锁。总共使用了来自斯坦福亚太高血压和胰岛素抵抗计划家族研究的 1365 名非糖尿病中国个体，以寻找与肥胖相关特征相关的数量性状基因座（QTL）。还使用双变量连锁分析方法检查了来自 QTL 的多效性和巧合效应。我们发现，大多数这些特征的遗传力和基因型性别相互作用效应都存在显著的性别差异。在将基因型性别（G×S）相互作用纳入连锁映射后，确定了几个具有强连锁证据的 QTL，包括一个臀围的 QTL（最大 LOD 评分（MLS）= 4.22，经验 p = 0.000033）和两个 QTL：12q 染色体上的 BMI，MLS 为 3.37（经验 p = 0.0043）和 3.10（经验 p = 0.0054）。性别特异性分析表明，这些连锁信号都来自女性，而不是男性。这些肥胖相关特征的大多数 QTL 都复制了其他种族群体的发现。双变量连锁分析表明，几个肥胖特征受一组共同的 QTL 影响。所有具有连锁信号的区域都在一个性别中观察到，而不是在整个样本中，这表明肥胖相关特征的遗传结构确实因性别而异。这些发现有助于通过候选基因或全基因组关联分析进一步确定这些表型的易感性基因。
