Abstract
We report the results of statistical genetic analyses of data from the Collaborative Study on the Genetics of Alcoholism prepared for the Genetic Analysis Workshop 14 to detect and characterize maternally inherited mitochondrial genetic effects on variation in latent class psychiatric/behavioral variables employed in the diagnosis of alcoholism. Using published extensions to variance decomposition methods for statistical genetic analysis of continuous and discrete traits we: 1) estimated the proportion of the variance in each trait due to the effects of mitochondrial DNA (mtDNA), 2) tested for pleiotropy, both mitochondrial genetic and residual additive genetic, between trait pairs, and 3) evaluated whether the simultaneous estimation of mitochondrial genetic effects on these traits improves our ability to detect and localize quantitative trait loci (QTL) in the nuclear genome. After correction for multiple testing, we find significant (p < 0.009) mitochondrial genetic contributions to the variance for two latent class variables. Although we do detect significant residual additive genetic correlations between the two traits, there is no evidence of a residual mitochondrial genetic correlation between them. Evidence for autosomal QTL for these traits is improved when linkage screens are conditioned on significant mitochondrial genetic effects. We conclude that mitochondrial genes may contribute to variation in some latent class psychiatric/behavioral variables associated with alcoholism.
Highlights
A number of studies have report associations between mtDNA variation and chronic alcoholism
Data The Collaborative Study of the Genetics of Alcoholism (COGA) dataset for the Genetic Analysis Workshop 14 includes 1,614 individuals, 788 females and 826 males, aged 17–91 years, in 143 pedigrees of varying size and complexity
Bivariate genetic analysis of the two traits identified above yielded the following correlation estimates when no mitochondrial genetic component was included in the model: ρG = 0.06 ± 0.17, ρE = 0.24 ± 0.07, and ρP = 0.06
Summary
A number of studies have report associations between mtDNA variation and chronic alcoholism. A small number of studies have detected associations between mtDNA polymorphisms and psychiatric disorders and syndromes that overlap those of chronic alcoholism [3,4]. These observations, plus the possibility that heritable mtDNA mutations could influence susceptibility to alcohol-induced oxidative stress damage, motivate our current study in which we analyze data from the Collaborative Study of the Genetics of Alcoholism (COGA) [5] to detect and characterize mitochondrial genetic effects on variation in latent class psychiatric/behavioral variables.
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