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Chunk #32 — Discussion

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Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid alcohol and drug dependence.
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The major risk variants identified in the ND study delineate a haplotype spanning TTC12 and ANKK1. This haplotype is composed of four SNPs, T6-A1-A3-A5 (Figure 1), where T6 is very close to the identified risk region in TTC12 exon 3 from the other two studies, and the other 3 SNPs are located in the small ANKK1 region extending from intron 1 to exon 6. This study was analyzed by a different approach, without the “sliding window” exhaustive search for risk variants employed in the other two studies. The identified risk variants were very strongly supported in terms of their statistical significance and were close to the risk regions from the other two studies. In addition, since the ND sample was ascertained for a sib-pair linkage analysis for the primary traits of cocaine and opioid dependence, there is especially high comorbidity with DD in this sample.