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

Autor:	Siewert KM; Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Klarin D; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Boston VA Healthcare System, Boston, MA, USA., Damrauer SM; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA.; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Chang KM; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA.; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Tsao PS; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.; VA Palo Alto Health Care System, Palo Alto, CA, USA., Assimes TL; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.; VA Palo Alto Health Care System, Palo Alto, CA, USA., Davey Smith G; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK., Voight BF; Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	International journal of epidemiology [Int J Epidemiol] 2020 Jun 01; Vol. 49 (3), pp. 1022-1031.
DOI:	10.1093/ije/dyaa050
Abstrakt:	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. (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)
Databáze:	MEDLINE
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