Comparison of single-nucleotide polymorphisms and microsatellites in detecting quantitative trait loci for alcoholism: the Collaborative Study on the Genetics of Alcoholism

Abstract

Background: The feasibility of effectively analyzing high-density single nucleotide polymorphism (SNP) maps in whole genome scans of complex traits is not known. The purpose of this study was to compare variance components linkage results using different density marker maps in data from the Collaborative Study on the Genetics of Alcoholism (COGA). Marker maps having an average spacing of 10 cM (microsatellite), 0.78 cM (SNP1), and 0.31 cM (SNP2) were used to identify quantitative trait loci (QTLs) affecting maximum number of alcoholic drinks consumed in a 24-hour period (Inmaxalc).

Results: Heritability of Inmaxalc was estimated to be 15%. Multipoint variance components linkage analysis revealed similar linkage patterns among the three marker panels, with the SNP maps consistently yielding higher LOD scores. Robust LOD scores > 1.0 were observed on chromosomes 1 and 13 for all three marker maps. Additional LODs > 1.0 were observed on chromosome 4 with both SNP maps and on chromosomes 18 and 21 with the SNP2 map. Peak LOD scores for Inmaxalc were observed on chromosome 1, although none reached genome-wide statistical significance. Quantile-quantile plots revealed that the multipoint distribution of SNP results appeared to fit the asymptotic null distribution better than the twopoint results.

Conclusion: In conclusion, variance-components linkage analysis using high-density SNP maps provided higher LOD scores compared with the standard microsatellite map, similar to studies using nonparametric linkage methods. Widespread application of SNP maps will depend on further improvements in the computational methods implemented in current software packages.

Figure 1

Multipoint variance components LOD scores for log-transformed maximum number of alcoholic drinks per day (lnmaxalc), by marker panel. Adjusted for age, sex, and ethnicity; cM = sex-averaged distance from p-term.

Figure 2

Quantile-quantile plots of genome-wide LOD scores. Twopoint (A) and multipoint (B) genomewide LOD scores are plotted against the asymptotic null distribution (1/2 ; 1/2 point mass 0) for each marker map. The red vertical line corresponds to a LOD score of 1.5.