PubMed · 10665095
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E Gordis, R Fuller. 1999. Project MATCH.. https://pubmed.ncbi.nlm.nih.gov/10665095/
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Event-related brain potentials (ERPs) are altered in patients with a variety of psychiatric disorders and may represent quantitative correlates of disease liability that are more amenable to genetic analysis than disease status itself. Results of a genomewide linkage screen are presented for amplitude of the N4 and P3 components of the ERP, measured at 19 scalp locations in response to a semantic priming task for 604 individuals in 100 pedigrees ascertained as part of the Collaborative Study on the Genetics of Alcoholism. N4 and P3 amplitudes in response to three stimuli (nonwords, primed words [i.e., antonyms], and unprimed words) all showed significant heritabilities, the highest being.54. Both N4 and P3 showed significant genetic correlations across stimulus type at a given lead and across leads within a stimulus, indicating shared genetic influences among the traits. There were also substantial genetic correlations between the N4 and P3 amplitudes for a given lead, even across stimulus type. N4 amplitudes showed suggestive evidence of linkage in several chromosomal regions, and P3 amplitudes showed significant evidence of linkage to chromosome 5 and suggestive evidence of linkage to chromosome 4.
Numerous case-control studies have addressed the hypothesis that variant alleles of the dopamine D2 receptor gene (DRD2) increase the liability for alcohol and/or drug dependence, and both positive and negative results have been reported. Because population frequencies of these alleles vary considerably, the conflicting results could be due to population stratification bias. Using the transmission disequilibrium test, the present study examined linkage disequilibrium of alcohol and drug (opioid and/or cocaine) dependence with three DRD2 polymorphic systems: (a) TaqI A, (b) TaqI D, and (c) the functional -141CIns/Del promoter systems. DNA samples were collected from small nuclear families (SNFs), where one or more offspring met DSM-III-R or DSM-IV criteria for alcohol and/or drug dependence. Because positive association between DRD2 alleles and alcohol and/or drug dependence has been reported only in populations of European ancestry, we limited the present study to European Americans (EAs). No evidence for linkage disequilibrium was found for any of the polymorphic systems when examined in relation to any substance dependence, alcohol dependence (with or without drug dependence), or drug dependence (with or without alcohol dependence). These results are consistent with those from a recent family-based study of alcohol dependence. Together, these studies suggest that the conflicting findings from case-control studies of the association between alleles of DRD2 and substance dependence may be attributable to population stratification in some samples.
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