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Chunk #18 — METHODS — Molecular Methods and Analysis — Association analyses

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Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.
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The program Plink [Purcell et al., 2007] (http://pngu.mgh.harvard.edu/purcell/plink/) was used to conduct all association tests. Logistic regression association analyses using an additive genetic model were conducted on the combined phenotype defined by the presence of AD with CD or SUI. The association analyses were run on each of the 82,562 SNPs genotyped across chromosome 2, using as covariates sex and ethnicity, as defined based on principal component-based analysis performed in PLINK to cluster the samples along with HapMap reference samples. Additional details are available in [Edenberg et al., 2010]. There were 1,134 genes across the chromosome. We used a gene-based strategy for association testing, an approach which can offer the advantage of identifying association to genes where multiple common variants may exist, rather than focusing on a single SNP [Moskvina et al., 2009]. In previous studies of AD in the COGA sample, we have frequently observed multiple signals across the gene [e.g., Wang et al., 2004; Edenberg et al., 2007; Dick et al., 2008; Wetherill et al., 2008]. The observation of multiple (not entirely correlated) signals across a gene enhances our confidence that an observed association is real.