Cladistic association analysis of Y chromosome effects on alcohol dependence and related personality traits

Abstract

Association between Y chromosome haplotype variation and alcohol dependence and related personality traits was investigated in a large sample of psychiatrically diagnosed Finnish males. Haplotypes were constructed for 359 individuals using alleles at eight loci (seven microsatellite loci and a nucleotide substitution in the DYZ3 alphoid satellite locus). A cladogram linking the 102 observed haplotype configurations was constructed by using parsimony with a single-step mutation model. Then, a series of contingency tables nested according to the cladogram hierarchy were used to test for association between Y haplotype and alcohol dependence. Finally, using only alcohol-dependent subjects, we tested for association between Y haplotype and personality variables postulated to define subtypes of alcoholism-antisocial personality disorder, novelty seeking, harm avoidance, and reward dependence. Significant association with alcohol dependence was observed at three Y haplotype clades, with significance levels of P = 0.002, P = 0.020, and P = 0.010. Within alcohol-dependent subjects, no relationship was revealed between Y haplotype and antisocial personality disorder, novelty seeking, harm avoidance, or reward dependence. These results demonstrate, by using a fully objective association design, that differences among Y chromosomes contribute to variation in vulnerability to alcohol dependence. However, they do not demonstrate an association between Y haplotype and the personality variables thought to underlie the subtypes of alcoholism.

Figure 1

Unrooted Y chromosome cladogram. Phylogeny of 102 Y chromosome haplotypes inferred by using maximum parsimony. Haplotype relationships are displayed as an unrooted phylogram with branch lengths proportional to the number of mutational steps between haplotypes. Total number of steps in the tree is 130. Observed haplotypes are depicted as circles (filled or open) whose sizes reflect haplotype frequency. Numbers in black are haplotypes noted in the text. Haplotypes found on branches A and B possessed the DYZ3 HindIII site, whereas haplotypes on branch C lacked the site. Haplotypes observed in Swedish and European American males are labeled S and E, respectively. Two-step clades 2-11, 2-13, and 2-20 (outlined in blue) were significantly associated with alcohol dependence, P = 0.002, P = 0.020, and P = 0.010, respectively. The association was attributable to 1-step clades 1-49, 1-21 and 1-57 (outlined in red). Every individual in clade 1-57 (haplotype 35) was also diagnosed with ASPD.