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


CONCLUSIONS
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.
Libiger
Ondrej
O
Polymorphism Research Laboratory, Department of Psychiatry, The University of California, San Diego, La Jolla, California 92093-0603, USA. olibiger@ucsd.edu
Schork
Nicholas J
NJ
D000437:Alcoholism / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D003226:Congresses as Topic; D003241:Consanguinity; D003299:Cooperative Behavior; D030541:Databases, Genetic; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree