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. 2005 Dec 30;6 Suppl 1(Suppl 1):S35.
doi: 10.1186/1471-2156-6-S1-S35.

Simulation-based homozygosity mapping with the GAW14 COGA dataset on alcoholism

Ondrej Libiger  1 , Nicholas J Schork
Affiliations

Simulation-based homozygosity mapping with the GAW14 COGA dataset on alcoholism

Ondrej Libiger et al. BMC Genet. .

Abstract

Background: We have developed a simulation-based approach to the analysis of shared homozygous chromosomal segments and have applied it to data on allele sharing among alcoholics in a single Collaborative Study on the Genetics of Alcoholism pedigree. Our assessment of sharing involved the use of a single-nucleotide polymorphism (SNP) marker map provided by Affymetrix.

Results: All 11 affected individuals in the selected pedigree shared 2 copies of an allele at 4 adjacent SNPs in a region on chromosome 5. Via simulation, we determined that the probability that such sharing is caused by mere chance is less than 0.0000001. After correcting for undocumented inbreeding, this probability rose to 0.0016. The probability that the shared segment emanates from a single ancestor and is unrelated to the affection status is less than 0.0000001 in the corrected pedigree. Haplotype association analysis and a search for a protective locus using unaffected individuals yielded no significant results.

Conclusion: Homozygosity mapping results on chromosome 5 provide suggestive evidence of the region's role as one that may harbor a genetic determinant of alcoholism. Furthermore, the probabilities of chance homozygous allele sharing for the original and for the inbreeding-corrected pedigree provide insight into the impact that inbreeding can have on such calculations.

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Figures

Figure 1
Figure 1
COGA pedigree 10022. The 11 individuals with black shading were considered to be affected, the unshaded individuals in the last 2 generations (857, 191, and 658) were considered unaffected, and the gray individuals were treated as unknown. There was no available information about the phenotypes or genotypes of the 3 distinct founders in the first generation (268, 997, and 221). Note: The 2 circles in the first generation that are marked with an arrow represent a single individual.
Figure 2
Figure 2
The inbreeding-corrected pedigree. The second, third and fourth generations correspond to COGA pedigree 10022 depicted in Figure 1.
See this image and copyright information in PMC

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