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Chunk #134 — IV. Results of tests of clustering within individual samples and tests of convergence between replicate samples for the same phenotypes — A. Polysubstance dependence vs controls (Samples 1 and 2)

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Molecular genetics of addiction and related heritable phenotypes: genome-wide association approaches identify "connectivity constellation" and drug target genes with pleiotropic effects.
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NIDA substance dependence samples were analyzed [12] by selecting “nominally positive SNPs” that displayed p values < 0.05 for comparisons between substance dependent vs control samples in both European-American and African-American samples. We assessed the extent to which nominally-positive SNPs that were identified in both samples by SNPs represented on at least two different array types cluster together in small chromosomal regions. Clusters contain at least three SNPs that display p < 0.05 in both samples and lie within 100 kb of each other. In this dataset, 6,666 of the 639,401 tested SNPs displayed reproducible, nominally-significant abuser vs control allele frequency differences (p < 0.05) in both samples. The criterion that the same SNP display nominally-significant association in each of two samples is more stringent than criteria used in other comparisons (see below). This criterion was applied to reduce the number of false positive results, but does not allow as much within-locus heterogeneity. 1,158 of these 6,666 reproducibly-positive SNPs lie in 320 chromosomal clusters. 184 of these clusters identify 244 annotated genes.