Hsieh Hsin-Ju, Palmer Christina G S, Sinsheimer Janet S
Biostatistics, University of California, Los Angeles, CA, USA.
Hum Hered. 2006;62(3):165-74. doi: 10.1159/000096444. Epub 2006 Oct 25.
Genes can be associated with disease through an individual's inherited genotype, the maternal genotype or the interaction between these two. When the gene is highly polymorphic, it is more difficult to identify the gene's functional role than for less polymorphic loci, because different alleles at the locus may be associated with the disease through separate and joint effects from maternal and offspring genotypes. Family-based studies are used to test genetic associations because of their robustness to population stratification. However, parental genotype data are often missing, and omitting incompletely genotyped families is inefficient. Methods have been proposed to accommodate incomplete families in family-based association studies. They are not easily generalized to allow simultaneous examination of offspring allelic, maternal allelic and maternal-fetal genotype (MFG) incompatibility effects. Since many MFG incompatibility effects occur through matching between maternal and offspring's genotypes, we present an identity-by-state (IBS) framework to incorporate incomplete families in the MFG test when modeling genetic effects produced by a polymorphic gene. Using simulations, we examine the MFG test's performance with incomplete parental genotype data and an IBS framework. The MFG test using the IBS framework is immune to population stratification and efficiently uses information from incomplete families.
基因可通过个体的遗传基因型、母体基因型或两者之间的相互作用与疾病相关联。当基因具有高度多态性时，相较于低多态性位点，识别该基因的功能作用更为困难，因为该位点的不同等位基因可能通过母体和后代基因型的单独及联合效应与疾病相关。基于家系的研究因其对群体分层具有稳健性而被用于检验基因关联性。然而，亲本基因型数据常常缺失，并且遗漏不完全基因分型的家系效率低下。已有人提出在基于家系的关联研究中处理不完全家系的方法。但这些方法不易推广以同时检验后代等位基因、母体等位基因和母胎基因型（MFG）不相容性效应。由于许多MFG不相容性效应是通过母体和后代基因型之间的匹配产生的，因此我们提出了一种状态相同（IBS）框架，以便在对多态性基因产生的遗传效应进行建模时，将不完全家系纳入MFG检验。通过模拟，我们使用不完全亲本基因型数据和IBS框架检验了MFG检验的性能。使用IBS框架的MFG检验不受群体分层影响，并能有效利用来自不完全家系的信息。
