GENETIC SUSCEPTIBILITY LOCI IN GENOME-WIDE ASSOCIATION STUDY OF CLUSTER HEADACHE 131 6 p-value 8.98 x 10-13; rs12121134 (EA: T), OR 1.40 (95% CI 1.29-1.53), p-value 9.18 x 10-15; rs6541998 (EA: C), OR 1.40 (95% CI 1.30-1.51), p-value 2.37 x 10-19; rs4519530 (EA: C), OR 1.41 (95% CI 1.31-1.52), p-value 4.18 x 10-29; rs10184573 (EA: T), OR 1.38 (95% CI 1.28-1.50), p-value 3.35 x 10-16; rs113658130 (EA: C), OR 1.54 (95% CI 1.41-1.69), p-value 1.28 x 10-21; rs2499799 (EA: C), OR 0.77 (95% CI 0.70-0.84), p-value 2.73 x 10-8; rs11153082 (EA: G), OR 1.33 (95% CI 1.23-1.43), p-value 2.98 x 10-14. The eight index variants in the overlapping loci showed a consistent effect direction across the two studies. Colocalization analysis, to determine whether the reported loci of both manuscripts represent the same causal variants, identified a high posterior probability for three loci (those on chromosomes 1 and 2) to likely represent the same causal variant.33 Rs12121134 and rs11579212 have a posterior probability that the causal variants are the same (H4) of 80.4%, for rs4519530 and rs6541998 H4 is 87.4% and for rs113658130 and rs10184573 H4 is 96.9%. For the locus on chromosome 6, the colocalization analysis shows a higher probability that the loci in the two studies represent distinct causal variants (H3: 78.7%) rather than the same causal variant (H4: 21.2%). Finally, the meta-analysis resulted in three additional loci becoming genome-wide significant: (1) a locus on chromosome 7 with 31 significant (p-value < 5 x 10-8) variants with index variant rs6966836 (chr7:117002998, EA: C), OR 1.25 (95% CI 1.16-1.35), p-value 2.06 x 10-9; (2) a locus on chromosome 10 with two significant variants with index variant rs10786156 (chr10:96014622, EA: C), OR 1.24 (95% CI 1.15-1.33), p-value 7.61 x 10-9; and (3) a locus on chromosome 19 with two significant variants with index variant rs60690598 (chr19:55052198, EA: T), OR 1.87 (95% CI 1.51-2.33), p-value 1.70 x 10-8.
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