Dong Chuanhui, Li Wei-Dong, Li Ding, Price R Arlen
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Eur J Hum Genet. 2005 Jan;13(1):102-8. doi: 10.1038/sj.ejhg.5201292.
One of the chief complexities of genetic influences on human obesity appears to be gene-gene interactions. Here, we employed model-free approaches to look for gene-gene interaction effects in human obesity using genome scan data from 260 European American families. We found consistent evidence for statistical interaction between 2p25-p24 (18-38 cM) and 13q13-q21 (26-47 cM). For discrete traits, the positive correlations were significant at P<0.0001 (P</=0.0023 after correction for multiple tests) in both IBD-based and NPL-based analyses for BMI>/=40 kg/m(2). Other analytic approaches gave consistent, supportive results. For quantitative traits, interaction effects were significant for BMI (P=0.0012), percent fat (P=0.0265) and waist circumference (P=0.0023) in a Haseman-Elston regression model, and for BMI (P=0.0043) in variance component analysis. Our findings suggest that obesity-susceptibility loci in chromosome regions 2p25-p24 and 13q13-21 may interact to influence extreme human obesity. The identification of gene-gene interactions may prove crucial to understanding the contributions of genes, which, by themselves, have relatively small effects on obesity susceptibility and resistance.
基因对人类肥胖影响的主要复杂性之一似乎是基因与基因之间的相互作用。在此，我们采用无模型方法，利用来自260个欧美家庭的基因组扫描数据，寻找人类肥胖中的基因与基因相互作用效应。我们发现2p25 - p24（18 - 38厘摩）和13q13 - q21（26 - 47厘摩）之间存在统计学相互作用的一致证据。对于离散性状，在基于IBD和基于NPL的分析中，当BMI≥40 kg/m²时，正相关性在P<0.0001时显著（经多重检验校正后P≤0.0023）。其他分析方法给出了一致的支持性结果。对于数量性状，在Haseman - Elston回归模型中，BMI（P = 0.0012）、体脂百分比（P = 0.0265）和腰围（P = 0.0023）的相互作用效应显著，在方差成分分析中BMI（P = 0.0043）的相互作用效应显著。我们的研究结果表明，染色体区域2p25 - p24和13q13 - 21中的肥胖易感基因座可能相互作用，影响极端人类肥胖。基因与基因相互作用的识别可能对理解基因的作用至关重要，这些基因本身对肥胖易感性和抗性的影响相对较小。
