Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache

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The International Headache Genetics Consortium , Siewert , K M , Klarin , D , Damrauer , S M , Chang , K M , Tsao , P S , Assimes , T L , Smith , G D , Voight , B F , Anttila , V , Palta , P , Muona , M , Kallela , K M , Koiranen , M , Lehtimäki , T , Sarin , A-P , Wedenoja , J , Färkkilä , M , Artto , V , Kaunisto , M , Vepsäläinen , S , Kurki , M I , Hämäläinen , E I , Eriksson , J G , Salomaa , V , Heikkilä , K , Männikkö , M , Hiekkala , M , Kajanne , R , Kaprio , J , Aromaa , A J , Raitakari , O , Järvelin , M-R , Wessman , M & Palotie , A 2021 , ' Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache ' , International Journal of Epidemiology , vol. 49 , no. 3 , pp. 1022-1031 .

Title: Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache
Author: The International Headache Genetics Consortium; Siewert, Katherine M.; Klarin, Derek; Damrauer, Scott M.; Chang, Kyong Mi; Tsao, Philip S.; Assimes, Themistocles L.; Smith, George Davey; Voight, Benjamin F.; Anttila, Verneri; Palta, Priit; Muona, Mikko; Kallela, Kaarlo Mikko; Koiranen, Markku; Lehtimäki, Terho; Sarin, Antti-Pekka; Wedenoja, Juho; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Kurki, Mitja Ilari; Hämäläinen, Eija Inkeri; Eriksson, Johan G.; Salomaa, Veikko; Heikkilä, Kauko; Männikkö, Minna; Hiekkala, Marjo; Kajanne, Risto; Kaprio, Jaakko; Aromaa, Arpo J.; Raitakari, Olli; Järvelin, Marjo-Riitta; Wessman, Maija; Palotie, Aarno
Contributor organization: Institute for Molecular Medicine Finland
Genomics of Neurological and Neuropsychiatric Disorders
HUS Neurocenter
Department of Neurosciences
Department of Public Health
Neurologian yksikkö
HUS Helsinki and Uusimaa Hospital District
Research Programs Unit
Johan Eriksson / Principal Investigator
Department of General Practice and Primary Health Care
Centre of Excellence in Complex Disease Genetics
Aarno Palotie / Principal Investigator
Date: 2021
Language: eng
Number of pages: 10
Belongs to series: International Journal of Epidemiology
ISSN: 0300-5771
Abstract: Background: Nearly a fifth of the world's population suffer from migraine headache, yet risk factors for this disease are poorly characterized. Methods: To further elucidate these factors, we conducted a genetic correlation analysis using cross-trait linkage disequilibrium (LD) score regression between migraine headache and 47 traits from the UK Biobank. We then tested for possible causality between these phenotypes and migraine, using Mendelian randomization. In addition, we attempted replication of our findings in an independent genome-wide association study (GWAS) when available. Results: We report multiple phenotypes with genetic correlation (P < 1.06 × 10-3) with migraine, including heart disease, type 2 diabetes, lipid levels, blood pressure, autoimmune and psychiatric phenotypes. In particular, we find evidence that blood pressure directly contributes to migraine and explains a previously suggested causal relationship between calcium and migraine. Conclusions: This is the largest genetic correlation analysis of migraine headache to date, both in terms of migraine GWAS sample size and the number of phenotypes tested. We find that migraine has a shared genetic basis with a large number of traits, indicating pervasive pleiotropy at migraine-associated loci.
Subject: Genetic correlation
Mendelian randomization
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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