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Chunk #35 — Discussion — Candidate Gene Analysis

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Genomewide association analysis of symptoms of alcohol dependence in the molecular genetics of schizophrenia (MGS2) control sample.
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Two genes which had previously shown association with AD in the large COGA sample were also broadly replicated in the EA sample, with analyses producing encouraging results with ANKK1 (ankyrin repeat and kinase domain containing 1; p=0.068) and NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; p=0.024). Studies in the COGA sample had reported nominal association with two SNPs in ANKK1 (p=0.03) (Dick et al. 2007) and examination of NFKB1 had shown experiment-wide significant association (p=0.01), after correction for multiple testing. Just as replication of previously reported candidate genes is necessary to assess the validity of the findings, results of GWAS also need to be tested in other samples and our set-based analyses provided supporting evidence for PECR (peroxisomal trans-2-enoyl-CoA reductase). One SNP (rs7590720) produced genome-wide significance with P=9.72×10-9 in a German sample (Treutlein et al. 2009). Although no single SNP produced p<10-3 in our study, gene-wise permutation produced a trend result: p=0.06.