Haplotype-sharing analysis for alcohol dependence based on quantitative traits and the Mantel statistic

Abstract

Haplotype-based methods have become increasingly popular in the last decade because shared lengths in haplotypes can be used for disease localization. In this contribution, we propose a novel linkage-based haplotype-sharing approach for quantitative traits based on the class of Mantel statistics which is closely related to the weighted pair-wise correlation statistic. Because these statistics are known to be liberal, we propose a permutation test to evaluate significance. We applied the Mantel statistic to the autosomal data from the genome-wide scan of the Collaborative Study on the Genetics of Alcoholism with the Affymetrix Genotype 10 K array that was provided for the Genetic Analysis Workshop 14. Four regions on chromosome 4, 8, 16, and 20 showed p-values less than 0.005 with a minimum p-value of < 0.0001 on chromosome 16 (tsc0520638 at 72.8 cM). Three of these four regions located on chromosome 4, 16, and 20 have been reported previously in the Genetic Analysis Workshop 11.

Figure 1

Selected region after second step of analysis for chromosome 4 (a), chromosome 8 (b), chromosome 16 (c), and chromosome 20 (d).