GENETIC SUSCEPTIBILITY LOCI IN GENOME-WIDE ASSOCIATION STUDY OF CLUSTER HEADACHE 127 6 Table 3 Replication of the significant loci in an independent sample L Chr SNP discovery sample SNP replication sample Posa OR [95% CI] P-valueb Directionc 1 1 rs11579212 rs11579212 222072819 1.58 [1.16-2.15] 3.50 x 10-3 + 2 2 rs6541998 rs6541998 112785237 1.04 [0.78-1.40] 0.78 + 3 2 rs10184573 rs10184573 200448253 1.74 [1.29-2.34] 2.78 x 10-4 + 4 6 rs2499799 rs976357 (r2=1.0) 96849679 0.44 [0.30-0.64] 2.76 x 10-5 + a Chromosomal positions in GRCh37/hg19 coordinates for the replication SNP. b Significant result (p < 0.05/4). c Direction; Same (+) or opposite (-) direction of association for discovery and replication analyses. L = locus number; Chr = chromosome; SNP = single nucleotide polymorphism; Pos = chromosomal position; OR = odds ratio; CI = confidence interval. Table 4 The association of previously reported cluster headache loci in our discovery cluster headache sample Previously reported CH loci Association with CH discovery sample Nearest coding gene Index SNP EA OR [95%CI] P-value Ref OR [95%CI] Pcorrvaluea ADCYAP1R1 rs12668955 G 0.48 [0.34-0.07] 9.1 × 10-6 [13] 1.05 [0.91-1.21] 1 ADH4 rs1126671 A 2.33 [1.25-4.37] 0.006b [30] 0.87 [0.76-0.99] 0.36 ADH4 rs1126671 A - 0.03 [31] 0.87 [0.76-0.99] 0.36 ADH4 rs1800759 A - 0.03 [31] 0.80 [0.70-0.90] 0.0035 CLOCK rs12649507 A 1.29 [1.08-1.54] 0.02 [29] 0.92 [0.80-1.05] 1 CHRNA3CHRNA5 rs578776 A - 0.038 [27] 0.95 [0.83-1.09] 1 HCRTR2 rs2653349 G 6.79 [2.25-22.99] < 0.0002 [8] 1.08 [0.93-1.26] 1 HCRTR2 rs2653349 G 1.97 [1.32-2.92] 0.0007 [10] 1.08 [0.93-1.26] 1 HCRTR2 rs3122156 G 0.82 [0.68-0.99] 0.0421 (Pcorr 0.126) [9] 0.92 [0.80-1.06] 1 HCRTR2 rs10498801 G 0.69 [0.49-0.97] 0.030 [28] 1.03 [0.88-1.21] 1 MME rs147564881 C - 0.019 [13] 0.24 [0.42-41.51] 1 The SNPs previously reported to be associated with cluster headache and the corresponding OR (based on the same EA) and p-values for these SNPs in the discovery sample. a P-values were Bonferroni corrected for 9 tests. b P-value is based on the carriers with homozygous AA genotype compared with GG/GA genotypes. CH = cluster headache; SNP = single nucleotide polymorphism; EA = effect allele; OR = odds ratio; CI = confidence interval
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