DESCRIPTION:

List of positional candidate genes identified by clusters of SNPs that provide nominally-significant differences between individuals dependent on alcohol or at least one illegal substance in subjects of European-American heritage. Number of SNPs uploaded.

LABEL:

European GWAS Alcohol OR 1 drug

SCORE TYPE:

Effect

DATE ADDED:

None

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Johnson C, Drgon T, Walther D, Uhl GR

TITLE:

Genomic regions identified by overlapping clusters of nominally-positive SNPs from genome-wide studies of alcohol and illegal substance dependence.

JOURNAL:

PloS one None 2011, Vol 6, pp. e19210

ABSTRACT:

Declaring \"replication\" from results of genome wide association (GWA) studies is straightforward when major gene effects provide genome-wide significance for association of the same allele of the same SNP in each of multiple independent samples. However, such unambiguous replication is unlikely when phenotypes display polygenic genetic architecture, allelic heterogeneity, locus heterogeneity and when different samples display linkage disequilibria with different fine structures. We seek chromosomal regions that are tagged by clustered SNPs that display nominally-significant association in each of several independent samples. This approach provides one \"nontemplate\" approach to identifying overall replication of groups of GWA results in the face of difficult genetic architectures. We apply this strategy to 1 M SNP GWA results for dependence on: a) alcohol (including many individuals with dependence on other addictive substances) and b) at least one illegal substance (including many individuals dependent on alcohol). This approach provides high confidence in rejecting the null hypothesis that chance alone accounts for the extent to which clustered, nominally-significant SNPs from samples of the same racial/ethnic background identify the same sets of chromosomal regions. It identifies several genes that are also reported in other independent alcohol-dependence GWA datasets. There is more modest confidence in: a) identification of individual chromosomal regions and genes that are not also identified by data from other independent samples, b) the more modest overlap between results from samples of different racial/ethnic backgrounds and c) the extent to which any gene not identified herein is excluded, since the power of each of these individual samples is modest. Nevertheless, the strong overlap identified among the samples with similar racial/ethnic backgrounds supports contributions to individual differences in vulnerability to addictions that come from newer allelic variants that are common in subsets of current humans. PUBMED: 21818250
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