The other two significant SNPs to emerge from the two-stage association analysis are rs2294015, a non-synonymous variant of ANXA13 that encodes a phospholipid-binding protein involved in cellular growth and signal transduction (coefficients of 0.21 ± 0.05 μV and 0.09 ± 0.05 μV), and intronic rs7916403 from serotonin receptor gene HTR7 (effect sizes of 0.10 ± 0.05 μV and 0.17 ± 0.05 μV for the T allele). All four implicated SNPs were tested for association with alcohol dependence, with only rs7916403 showing a significant relationship to the disease under a recessive mode of genetic influence, with estimated ORs of 1.32 (P = 0.036) and 1.37 (P = 0.042) in the two samples (similar OR scores were observed for the European-American subsets). Haplotype-based testing of a 5.8 kb LD block encompassing the HTR7 variant lends support to this finding, revealing a significant joint-association to alcohol dependence (P = 0.0074) that weakens when the effects of rs7916403 are controlled for (P = 0.098).
