Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S162. doi: 10.1186/1471-2156-6-S1-S162.
Alcohol dependence is a typical example of a complex trait that is governed by several genes and for which the mode of inheritance is unknown. We analyzed the microsatellite markers and the Affymetrix single-nucleotide polymorphisms (SNPs) for a subset of the Collaborative Study on the Genetics of Alcoholism family sample, 93 pedigrees of Caucasian ancestry comprising 919 persons, 390 of whom are affected according to DSM III-R and Feighner criteria. In particular, we performed parametric single-marker linkage analysis using MLINK of the LINKAGE package (for the microsatellite data), as well as multipoint MOD-score analysis with GENEHUNTER-MODSCORE (for the microsatellite and SNP data). By use of two liability classes, different penetrances were assigned to males and females. In order to investigate parent-of-origin effects, we calculated MOD scores under trait models with and without imprinting. In addition, for the microsatellite data, the MOD-score analysis was performed with sex-averaged as well as sex-specific maps. The highest linkage peaks were obtained on chromosomes 1, 2, 7, 10, 12, 13, 15, and 21. There was evidence for paternal imprinting at the loci on chromosomes 2, 10, 12, 13, 15, and 21. A tendency to maternal imprinting was observed at two loci on chromosome 7. Our findings underscore the fact that an adequate modeling of the genotype-phenotype relation is crucial for the genetic mapping of a complex trait.
酒精依赖是一种典型的复杂特征，受多个基因控制，其遗传模式未知。我们分析了协作酒精中毒遗传学研究（Collaborative Study on the Genetics of Alcoholism）家族样本的微卫星标记和 Affymetrix 单核苷酸多态性（SNP），这些样本来自于 93 个具有高加索血统的家系，共包含 919 人，其中 390 人根据 DSM III-R 和 Feighner 标准被诊断为受影响者。特别是，我们使用 LINKAGE 包中的 MLINK（用于微卫星数据）进行了参数单标记连锁分析，以及使用 GENEHUNTER-MODSCORE（用于微卫星和 SNP 数据）进行多点 MOD 评分分析。通过使用两个易感性类别，为男性和女性分配了不同的外显率。为了研究亲本来源效应，我们在没有印记和有印记的特征模型下计算了 MOD 评分。此外，对于微卫星数据，还使用性别平均和性别特异性图谱进行了 MOD 评分分析。最高的连锁峰位于染色体 1、2、7、10、12、13、15 和 21 上。在染色体 2、10、12、13、15 和 21 上的多个位点存在父系印记的证据。在染色体 7 上的两个位点观察到母系印记的趋势。我们的研究结果强调了这样一个事实，即对基因型-表型关系进行适当建模对于复杂特征的遗传作图至关重要。
