Genome-wide linkage analysis of age at onset of alcohol dependence: a comparison between microsatellites and single-nucleotide polymorphisms.

Background: Using the dataset provided for Genetic Analysis Workshop 14 by the Collaborative Study on the Genetics of Alcoholism, we performed genome-wide linkage analysis of age at onset of alcoholism to compare the utility of microsatellites and single-nucleotide polymorphisms (SNPs) in genetic linkage study.

Methods: A multipoint nonparametric variance component linkage analysis method was applied to the survival distribution function obtained from semiparametric proportional hazards model of the age at onset phenotype of alcoholism. Three separate linkage analyses were carried out using 315 microsatellites, 2,467 and 9,467 SNPs, spanning the 22 autosomal chromosomes.

Results: Heritability of age at onset was estimated to be approximately 12% (p < 0.001). We observed weak correlation, both in trend and strength, of genome-wide linkage signals between microsatellites and SNPs. Results from SNPs revealed more and stronger linkage signals across the genome compared with those from microsatellites. The only suggestive evidence of linkage from microsatellites was on chromosome 1 (LOD of 1.43). Differences in map densities between the two sets of SNPs used in this study did not appear to confer an advantage in terms of strength of linkage signals.

Conclusion: Our study provided support for better performance of dense SNP maps compared with the sparse microsatellite maps currently available for linkage analysis of quantitative traits. This better performance could be attributable to precise definition and high map resolutions achievable with dense SNP maps, thus resulting in increased power to detect possible loci affecting given trait or disease.