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Replication and meta‐analysis of common variants identifies a genome‐wide significant locus in migraine
Author(s) -
Esserlind A.L.,
Christensen A. F.,
Le H.,
Kirchmann M.,
Hauge A. W.,
Toyserkani N. M.,
Hansen T.,
Grarup N.,
Werge T.,
Steinberg S.,
Bettella F.,
Stefansson H.,
Olesen J.
Publication year - 2013
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12055
Subject(s) - genome wide association study , single nucleotide polymorphism , snp , migraine with aura , migraine , genetics , genetic association , medicine , aura , locus (genetics) , familial hemiplegic migraine , bioinformatics , genotype , biology , gene
Background and purpose Genetic factors contribute to the aetiology of the prevalent form of migraine without aura ( MO ) and migraine with typical aura ( MTA ). Due to the complex inheritance of MO and MTA , the genetic background is still not fully established. In a population‐based genome‐wide association study by C hasman et al . ( Nat Genet 2011: 43: 695–698), three common variants were found to confer risk of migraine at a genome‐wide significant level ( P < 5 × 10 −8 ). We aimed to evaluate the top association single nucleotide polymorphisms ( SNP s) from the discovery set by C hasman et al . in a primarily clinic‐based Danish and Icelandic cohort. Methods The top association SNP s were assessed in 2523 cases and 38 170 controls, and a meta‐analysis was performed, combining the discovery set with all the follow‐up studies. Finally the confirmed SNP s were assessed in a genotype–phenotype analysis. Results Two out of three SNP s that showed genome‐wide significant associations in the previous study: rs10166942 (near TRPM 8 ) and rs11172113 (in LRP 1 ) were significantly associated with migraine in the present study. The meta‐analysis confirmed the previous three genome‐wide significant associated SNP s (rs2651899, rs10166942 and rs11172113) to confer risk of migraine. In addition, the C‐allele of rs2078371 (near TSPAN ‐2 ) also reached genome‐wide significance for association with migraine [ OR = 1.14; CI = (1.09–1.20); P = 2.55 × 10 −8 ]. Conclusion TSPAN ‐2 encodes an integral membrane protein involved in oligodendrogenesis. This new finding supports the plausible implication of neuroglia in the pathophysiology of MO and MTA .