Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Winsvold BS; Sigurdardottir GR; Kahonen M; Ran C; Kurth T; Farkkila M; Belin AC; Gormley P; Sveinsson OA; Ripatti S; Hrafnsdottir MG; Magnusson SH; Widen E; Aromaa A; van Dijk KW; Rosendaal FR; Ullum H; Buring JE; de Boer I; Skogholt AH; Ikram MA; Banasik K; Hautakangas H; Hottenga JJ; Nyholt DR; Noordam R; Dichgans M; Thomas LF; Wessman M; Chalmer MA; van den Maagdenberg AMJM; Freilinger T; Olesen J; Kallela M; Thorgeirsson TE; Bjornsdottir A; Hveem K; Kogelman LJA; Zwart JA; Penninx BWJH; Raitakari OT; Stefansson K; Hansen TF; Burgdorf KS; Hagen K; Garbrielsen ME; Benner C; Johnsen MB; Pedersen OB; Harder AVE; Lighart L; Malik R; Ruotsalainen SE; Ghanbari M; Vijfhuizen LS; Kristoffersen ES; Lehtimaki T; Pelzer N; Ridker PM; Happola P; Jarvelin MR; Pirinen M; Chasman DI; Bjornsdottir G; Brumpton B; Terwindt GM; Boomsma DI; Erikstrup C; Stefansson H; Artto V; Palotie A
Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Winsvold BS
Sigurdardottir GR
Kahonen M
Ran C
Kurth T
Farkkila M
Belin AC
Gormley P
Sveinsson OA
Ripatti S
Hrafnsdottir MG
Magnusson SH
Widen E
Aromaa A
van Dijk KW
Rosendaal FR
Ullum H
Buring JE
de Boer I
Skogholt AH
Ikram MA
Banasik K
Hautakangas H
Hottenga JJ
Nyholt DR
Noordam R
Dichgans M
Thomas LF
Wessman M
Chalmer MA
van den Maagdenberg AMJM
Freilinger T
Olesen J
Kallela M
Thorgeirsson TE
Bjornsdottir A
Hveem K
Kogelman LJA
Zwart JA
Penninx BWJH
Raitakari OT
Stefansson K
Hansen TF
Burgdorf KS
Hagen K
Garbrielsen ME
Benner C
Johnsen MB
Pedersen OB
Harder AVE
Lighart L
Malik R
Ruotsalainen SE
Ghanbari M
Vijfhuizen LS
Kristoffersen ES
Lehtimaki T
Pelzer N
Ridker PM
Happola P
Jarvelin MR
Pirinen M
Chasman DI
Bjornsdottir G
Brumpton B
Terwindt GM
Boomsma DI
Erikstrup C
Stefansson H
Artto V
Palotie A
Katso/Avaa
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NATURE PORTFOLIO
doi:10.1038/s41588-021-00990-0
URI
https://www.nature.com/articles/s41588-021-00990-0
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2022081153952
Tiivistelmä
Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants.Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
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