Ankra-Badu G A, Pomp D, Shriner D, Allison D B, Yi N
Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Int J Obes (Lond). 2009 Jan;33(1):89-95. doi: 10.1038/ijo.2008.215. Epub 2008 Nov 4.
The genetic architecture of body weight and body composition is complex because these traits are normally influenced by multiple genes and their interactions, even after controlling for the environment. Bayesian methodology provides an efficient way of estimating these interactions.
We used Bayesian model selection techniques to simultaneously estimate the main effects, epistasis and gene-sex interactions on age-related body weight (at 3, 6 and 10 weeks, denoted as WT3wk, WT6wk and WT10wk) and body composition (organ weights and fat-related traits) in an F(2) sample obtained from a cross between high-growth (M16i) mice and low-growth (L6) mice.
We observed epistatic and main-effect quantitative trait loci (QTL) that controlled both body weight and body composition. Epistatic effects were generally more significant for WT6wk than WT10wk. Chromosomes 5 and 13 interacted strongly to control body weight at 3 weeks. A pleiotropic QTL on chromosome 2 was associated with body weight and some body composition phenotypes. Testis weight was regulated by a QTL on chromosome 13 with a significantly large main effect (2log(e)BF approximately 15).
By analyzing epistatic interactions, we detected QTL not found in a previous analysis of this mouse population. Hence, the detection of gene-gene interactions may provide new information about the genetic architecture of complex obesity-related traits and may lead to the detection of additional obesity genes.
体重和身体成分的遗传结构很复杂，因为即使在控制了环境因素之后，这些性状通常仍受多个基因及其相互作用的影响。贝叶斯方法提供了一种估计这些相互作用的有效途径。
我们使用贝叶斯模型选择技术，在从高生长（M16i）小鼠和低生长（L6）小鼠杂交获得的F(2)样本中，同时估计与年龄相关的体重（3周、6周和10周时的体重，分别记为WT3wk、WT6wk和WT10wk）和身体成分（器官重量和脂肪相关性状）的主效应、上位性和基因-性别相互作用。
我们观察到控制体重和身体成分的上位性和主效应数量性状位点（QTL）。对于WT6wk，上位性效应通常比WT10wk更显著。第5号和第13号染色体强烈相互作用，控制3周时的体重。第2号染色体上的一个多效性QTL与体重和一些身体成分表型相关。睾丸重量受第13号染色体上一个QTL的调控，其主效应显著大（2log(e)BF约为15）。
通过分析上位性相互作用，我们检测到了在先前对该小鼠群体的分析中未发现的QTL。因此，基因-基因相互作用的检测可能为复杂的肥胖相关性状的遗传结构提供新信息，并可能导致发现更多的肥胖基因。
