Associations of Prenatal Nicotine Exposure and the Dopamine Related Genes ANKK1 and DRD2 to Verbal Language

... same variability in the locus. Interestingly, the ANKK1 haplotype block contained a marker in the DRD2 gene located adjacent to ANKK1 (rs6278) ( Figure 1 ). These associations persisted when examined in ALSPAC subjects not exposed to prenatal nicotine ( Table 7 ). There was no evidence of interaction between prenatal nicotine exposure and ND variants in the ALSPAC sample. Associations of SNPs within ANKK1 (rs2734849 and rs11604671) were replicated in the Iowa LI cohort with LI case-control status (OR=1.4 [1.12.0]; p7.4110 3 ) ( Table 9 ). 10.1371/journal.pone.0063762.g001 Figure 1 Linkage disequilibrium between ANKK1 and DRD2 . Linkage disequilibrium (LD), as measured by D, among markers in the ANKK1 and DRD2 genes. There is a 12kb haplotype block spanning the two genes (markers: rs11604671, rs2734849, rs1800497, and rs6278). 10.1371/journal.pone.0063762.t007 Table 7 Single marker genetic associations with average of Nonword Repetition and Verbal Comprehension tasks. Variant Gene p-value No SMK p-value a rs2734849 ANKK1 2.010 4 1.910 4 rs11604671 ANKK1 2.310 4 2.210 4 rs4938013 ANKK1 1.210 3 6.810 4 rs7118900 ANKK1 1.210 3 1.210 3 rs1800497 ANKK1 1.910 3 2.610 3 rs6278 DRD2 8.810 3 1.710 2 a No SMKg p-value refer to associations in cohort of subjects not exposed to prenatal nicotine. 10.1371/journal.pone.0063762.t008 Table 8 Haplotype Association of ANKK1 / DRD2 with average of Nonword Repetition and Verbal Comprehension tasks. Variants Genes Haplotype Beta p-value rs11604671, rs2734849, rs1800497, rs6278 ANKK1 / DRD2 ACCG 0.053 3.210 4 10.1371/journal.pone.0063762.t009 Table 9 Replication of genetic associations in Iowa LI cohort. Variant Gene Trait p-value OR rs11604671 ANKK1 Case-Control 3.8410 3 1.4 (1.12.0) rs2734849 ANKK1 Case-Control 7.4110 3 1.4 (1.12.0) rs1800497 ANKK1 Case-Control 1.910 2 1.5 (1.12.1) rs11604671 ANKK1 GORT Comp 3.310 2 N/A rs11604671 ANKK1 PPVT 2.510 2 N/A Abbreviations: OR, odds ratio; GORT Comp, Gray Oral Reading Test Comprehension; PPVT, Peabody

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