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. 2005 Dec 30;6 Suppl 1(Suppl 1):S162.
doi: 10.1186/1471-2156-6-S1-S162.

Linkage analysis of alcohol dependence using MOD scores

Konstantin Strauch  1 , Robert Fürst, Franz Rüschendorf, Christine Windemuth, Johannes Dietter, Antonia Flaquer, Max P Baur, Thomas F Wienker
Affiliations

Linkage analysis of alcohol dependence using MOD scores

Konstantin Strauch et al. BMC Genet. .

Abstract

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.

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Figures

Figure 1
Figure 1
MOD-score results for microsatellite markers. Genome-wide plot of the GENEHUNTER-MODSCORE results for the microsatellite markers using the sex-specific map. The red graph shows the MOD scores obtained under four-penetrance trait models that take imprinting into account, and the blue graph shows the MOD scores obtained under the nonimprinting constraint.
Figure 2
Figure 2
MOD-score results for Affymetrix SNP markers. Genome-wide plot of the GENEHUNTER-MODSCORE results for the Affymetrix SNP markers. The red graph shows the MOD scores obtained under four-penetrance trait models which take imprinting into account, and the blue graph shows the MOD scores obtained under the nonimprinting constraint. Here, a sex-averaged map has been used.
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