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

Katherine M Siewert, Derek Klarin, Scott M Damrauer, Kyong-Mi Chang, Philip S Tsao, Themistocles L Assimes, George Davey Smith, Benjamin F Voight*, The International Headache Genetics Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)1022-1031
Number of pages10
JournalInternational Journal of Epidemiology
Issue number3
Early online date19 Apr 2020
Publication statusPublished - 1 Jun 2020

Bibliographical note

© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.


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