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Chunk #39 — RESULTS — Haplotype-Based Association Analysis of Serotonin Receptor Gene HTR7

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Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.
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According to NCBI Build 36.3, the HTR7 gene is positioned between bp 92,490,555 and 92,607,651 on chromosome 10, with its three splice variants encoding either 3 or 4 exon regions and varying in the length of their carboxy terminal ends. A total of 35 SNPs encompassing HTR7 and its adjacent upstream and downstream regions (within 20 kb) met the QC standards in the GWAS. Of these, 22 SNPs capture all observed alleles at r2 ≥ 0.8 as determined by the program Tagger [de Bakker et al., 2005]. Based on the D’ confidence interval algorithm, five LD blocks were identified within the HTR7 gene, with rs7916403 incorporated into a 5.8 kb block in intron 1 that includes SNPs rs11186309 and rs1935351. Omnibus tests (H–1 degrees of freedom) were conducted on this LD block, revealing significant joint-haplotype association with alcohol dependence (P = 0.0074). When correcting for rs7916403, the association with alcoholism largely disappears (P = 0.098). Three alternate haplotypes were observed at this particular LD block (rs7916403-rs11186309-rs1935351), with G-T-G (frequency 0.51) producing a significant OR of 1.24 for alcohol dependence (P = 0.0081). When controlling for the G-T-G haplotype, the significant omnibus association with alcoholism once again disappears (P = 0.098).