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

doi:10.1093/ije/dyaa050

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

Bloomsburg University of Pennsylvania
Boston Children's Hospital and Harvard Medical School
Corporal Michael J Crescenz VA Medical Center Research
Stanford University School of Medicine
Bristol Medical School

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	1022-1031
Number of pages	10
Journal	International Journal of Epidemiology
Volume	49
Issue number	3
Early online date	19 Apr 2020
DOIs	https://doi.org/10.1093/ije/dyaa050
Publication status	Published - 1 Jun 2020

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SDG 3 Good Health and Well-being

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Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headacheFinal published version, 804 KBLicence: CC BY

Cite this

Siewert, K. M., Klarin, D., Damrauer, S. M., Chang, K.-M., Tsao, P. S., Assimes, T. L., Davey Smith, G., Voight, B. F., & The International Headache Genetics Consortium (2020). Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache. International Journal of Epidemiology, 49(3), 1022-1031. https://doi.org/10.1093/ije/dyaa050

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

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.",

author = "Siewert, \{Katherine M\} and Derek Klarin and Damrauer, \{Scott M\} and Kyong-Mi Chang and Tsao, \{Philip S\} and Assimes, \{Themistocles L\} and \{Davey Smith\}, George and Voight, \{Benjamin F\} and \{The International Headache Genetics Consortium\} and Hieab Adams and Elizabeth Loehrer and Andr{\'e} Uitterlinden and Bert Hofman and \{van Duijn\}, \{C.M. (Cornelia)\} and Arfan Ikram",

note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.",

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month = jun,

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doi = "10.1093/ije/dyaa050",

language = "English",

volume = "49",

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Siewert, KM, Klarin, D, Damrauer, SM, Chang, K-M, Tsao, PS, Assimes, TL, Davey Smith, G, Voight, BF & The International Headache Genetics Consortium 2020, '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. https://doi.org/10.1093/ije/dyaa050

TY - JOUR

T1 - Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache

AU - Siewert, Katherine M

AU - Klarin, Derek

AU - Damrauer, Scott M

AU - Chang, Kyong-Mi

AU - Tsao, Philip S

AU - Assimes, Themistocles L

AU - Davey Smith, George

AU - Voight, Benjamin F

AU - The International Headache Genetics Consortium

AU - Adams, Hieab

AU - Loehrer, Elizabeth

AU - Uitterlinden, André

AU - Hofman, Bert

AU - van Duijn, C.M. (Cornelia)

AU - Ikram, Arfan

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - 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.

AB - 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.

U2 - 10.1093/ije/dyaa050

DO - 10.1093/ije/dyaa050

M3 - Article

C2 - 32306029

SN - 0300-5771

VL - 49

SP - 1022

EP - 1031

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 3

ER -

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

Abstract

Bibliographical note

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