Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache
Siewert, Katherine M (University of Pennsylvania (Philadelphia, Estats Units d'Amèrica))
Klarin, Derek (Center for Genomic Medicine (Boston, Estats Units d'Amèrica))
Damrauer, Scott M (Universitat Autònoma de Barcelona. Departament de Cirurgia)
Chang, Kyong-Mi (University of Pennsylvania (Philadelphia, Estats Units d'Amèrica))
Tsao, Philip S (Stanford University School of Medicine (Standford, Estats Units d'América))
Assimes, Themistocles (Stanford University School of Medicine (Standford, Estats Units d'América))
Smith, George Davey (University of Bristol (Bristol, Estats Units d'Amèrica))
Voight, Benjamin (University of Pennsylvania (Philadelphia, Estats Units d'Amèrica))

Fecha:	2020
Resumen:	Nearly a fifth of the world's population suffer from migraine headache, yet risk factors for this disease are poorly characterized. 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. 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. 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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Genetic correlation ; Mendelian randomization ; Migraine ; Headache
Publicado en:	International journal of epidemiology, Vol. 49 (april 2020) , p. 1022-1031, ISSN 1464-3685

DOI: 10.1093/ije/dyaa050
PMID: 32306029

12 p, 720.7 KB

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