Comparison of genotype- and haplotype-based approaches for fine-mapping of alcohol dependence using COGA data.

It is generally assumed that the detection of disease susceptibility genes via fine-mapping association study is facilitated by consideration of marker haplotypes. In this study, we compared the performance of genotype-based and haplotype-based association studies using the Collaborative Study of Genetics of Alcoholism dataset, on several chromosomal regions showing evidence for linkage with ALDX1. After correction for multiple testing, the most significant results were observed with the genotype-based analyses on two regions of chromosomes 2 and 7. Interestingly, the analyses results from this dataset showed that there was no advantage of the haplotype-based analyses over genotype-based (single-locus) analyses. However, caution should be taken when generalizing these results to other chromosomal regions or to other populations.