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Chunk #28 — Results — Associations of CD with the positive variants identified in the EA family sample in the other three independent samples

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Interaction between two independent CNR1 variants increases risk for cocaine dependence in European Americans: a replication study in family-based sample and population-based sample.
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In the single-marker-wise analysis in EAs, we failed to observe that allele and genotype frequency distribution for SNP3 or SNP8 was significant differenct from controls (Table 3). However, as expected, in the EA case-control sample, the interaction between SNP3^G+ and SNP8^T/T significantly increased risk for CD (P=0.003) while adjusting for sex and age. This is consistent with our initial study, which showed that this interaction significantly increased risk for DD (P=0.0002), including CD (Table 2). Through permutation, haplotype trend regression (HTR) analysis using the Powermarker program showed a trend-level possible association between CD and the global haplotypes composed of these two SNPs (Pglobal= 0.069). Haplotype simulation association tests using Haplo.stats showed that global haplotypes and the GT haplotype (constructed from SNP3^G and SNP8^T) displayed significant association signals (Pglobal=0.054, PGT=0.018), adjusting for sex and age.