Whole-genome association studies on alcoholism comparing different phenotypes using single-nucleotide polymorphisms and microsatellites.
Alcoholism is a complex disease. As with other common diseases, genetic variants underlying alcoholism have been illusive, possibly due to the small effect from each individual susceptible variant, gene x environment and gene x gene interactions and complications in phenotype definition. We conducted association tests, the family-based association tests (FBAT) and the backward haplotype transmission association (BHTA), on the Collaborative Study of the Genetics of Alcoholism (COGA) data provided by Genetic Analysis Workshop (GAW) 14. Efron's local false discovery rate method was applied to control the proportion of false discoveries. For FBAT, we compared the results based on different types of genetic markers (single-nucleotide polymorphisms (SNPs) versus microsatellites) and different phenotype definitions (clinical diagnoses versus electrophysiological phenotypes). Significant association results were found only between SNPs and clinical diagnoses. In contrast, significant results were found only between microsatellites and electrophysiological phenotypes. In addition, we obtained the association results for SNPs and microsatellites using COGA diagnosis as phenotype based on BHTA. In this case, the results for SNPs and microsatellites are more consistent. Compared to FBAT, more significant markers are detected with BHTA.
Chen
Liang
L
Department of Epidemiology and Public Health, Yale University, New Haven, CT 06520, USA. liang.chen@yale.edu
Liu
Nianjun
N
Wang
Shuang
S
Oh
Cheongeun
C
Carriero
Nicholas J
NJ
Zhao
Hongyu
H
D000437:Alcoholism / Q000175:diagnosis / Q000235:genetics*; D003299:Cooperative Behavior; D005189:False Positive Reactions; D005190:Family; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*