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Chunk #13 — MATERIALS AND METHODS — Linkage Analyses

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Autosomal linkage scan for loci predisposing to comorbid dependence on multiple substances.
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Linkage analyses were carried out using the model-free regression method implemented in Merlin-regression [Sham et al., 2002]. This method is based on a modified Haseman–Elston method that regresses the estimated identity-by-descent sharing between relative pairs on the squared sums and squared differences of trait values of the relative pairs. Given that marker–marker linkage disequilibrium (LD) inflates multi-point linkage signals [Abecasis and Wigginton, 2005], SNPs were grouped by LD into clusters using the Merlin “—rsq” option of pairwise r2 > 0.10 to reduce linkage bias. We repeated the analyses with r2 thresholds of 0.05, 0.2, and 0.3 to evaluate the robustness of the linkage results.