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 alcoholismantisocial 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.

Early experience and serotonin transporter gene variation interact to influence primate CNS function

“…After the complete set of 10 000 pedigrees was simulated, the F-ratio above which the most extreme ␣100% of the simulated statistics lay was the empirical ␣100% significance level. With this procedure, [37][38][39] each random pedigree maintains the genotype and phenotype correlation structure that was inherent in the original sample, but there is no relationship between the genotype and phenotype, as stipulated by the null hypothesis.…”

Association Mapping With Single-Feature Polymorphisms

“…One could, for instance, successively test more inclusive clades. This idea is not directly helpful for LD mapping because the effects of recombination mean that the relationship between haplotypes is not tree-like (it might be used to test for phenotypic associations in nonrecombining data such as Y chromosomes, for example; see Kittles et al 1999). We require methods for estimating the treelike relationship at each point in a set of haplotypes (i.e., along the genome).…”

Association of the Human Y Chromosome with Cholesterol Levels in the General Population

“…Evidence for such a confounding influence of alcohol have been provided by investigations showing associations between alcoholism and certain variants of the human Y chromosome, 17 as well as studies suggesting correlation between alcohol consumption and lipid levels. 18,19 However, the current analysis does not seem to be affected by this confounder.…”