A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773)

Weihua Meng (Lead / Corresponding author), Mark J. Adams, Harry L. Hebert, Ian J. Deary, Andrew M. McIntosh, Blair H. Smith

Research output: Contribution to journalArticle

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Abstract

Background: Headache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort.
Methods: We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls.
Results: We identified 3,343 SNPs which reached the genome-wide significance level of P < 5 x 10-8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92 x 10-47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87 x 10-15 in the LINC02210-CRHR1 gene was the top SNP. Significant relationships between multiple brain tissues and genetic associations were identified through tissue expression analysis. We also identified significant positive genetic correlations between headache and many psychological traits.
Conclusions: Our results suggest that brain function is closely related to broadly-defined headache. In addition, we found that many psychological traits have genetic correlations with headache.
Original languageEnglish
Pages (from-to)180-186
Number of pages7
JournalEBioMedicine
Volume28
Early online date31 Jan 2018
DOIs
Publication statusPublished - Feb 2018

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Genome-Wide Association Study
Headache
Genes
Single Nucleotide Polymorphism
Brain
Tissue
Psychology
Migraine Disorders
Genome
Phenotype

Keywords

  • Genome-wide association study
  • Headache
  • LRP1
  • Tissue expression
  • UK biobank
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Headache/genetics
  • United Kingdom
  • Gene Expression Profiling
  • Genetic Loci
  • Case-Control Studies
  • Polymorphism, Single Nucleotide/genetics
  • Biological Specimen Banks
  • Linkage Disequilibrium/genetics
  • Cohort Studies

Cite this

@article{8477d68979864a8b8c75e82eaf45687d,
title = "A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773)",
abstract = "Background: Headache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort.Methods: We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls.Results: We identified 3,343 SNPs which reached the genome-wide significance level of P < 5 x 10-8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92 x 10-47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87 x 10-15 in the LINC02210-CRHR1 gene was the top SNP. Significant relationships between multiple brain tissues and genetic associations were identified through tissue expression analysis. We also identified significant positive genetic correlations between headache and many psychological traits.Conclusions: Our results suggest that brain function is closely related to broadly-defined headache. In addition, we found that many psychological traits have genetic correlations with headache.",
keywords = "Genome-wide association study, Headache, LRP1, Tissue expression, UK biobank, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Headache/genetics, United Kingdom, Gene Expression Profiling, Genetic Loci, Case-Control Studies, Polymorphism, Single Nucleotide/genetics, Biological Specimen Banks, Linkage Disequilibrium/genetics, Cohort Studies",
author = "Weihua Meng and Adams, {Mark J.} and Hebert, {Harry L.} and Deary, {Ian J.} and McIntosh, {Andrew M.} and Smith, {Blair H.}",
note = "This work was supported by the DOLORisk project [EU Horizon2020, grant number: 633491], the STRADL project [Wellcome Trust, grant number: 104036/Z/14/Z], and the Centre for Cognitive Ageing and Cognitive Epidemiology [Medical Research Council and Biotechnology and Biological Sciences Research Council, grant number: MR/K026992/1]. We are grateful for support from the the Dr Mortimer And Theresa Sackler Foundation. The funders had no role in study design, data collection, data analysis, interpretation, writing of the report.",
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A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773). / Meng, Weihua (Lead / Corresponding author); Adams, Mark J.; Hebert, Harry L.; Deary, Ian J.; McIntosh, Andrew M. ; Smith, Blair H.

In: EBioMedicine, Vol. 28, 02.2018, p. 180-186.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773)

AU - Meng, Weihua

AU - Adams, Mark J.

AU - Hebert, Harry L.

AU - Deary, Ian J.

AU - McIntosh, Andrew M.

AU - Smith, Blair H.

N1 - This work was supported by the DOLORisk project [EU Horizon2020, grant number: 633491], the STRADL project [Wellcome Trust, grant number: 104036/Z/14/Z], and the Centre for Cognitive Ageing and Cognitive Epidemiology [Medical Research Council and Biotechnology and Biological Sciences Research Council, grant number: MR/K026992/1]. We are grateful for support from the the Dr Mortimer And Theresa Sackler Foundation. The funders had no role in study design, data collection, data analysis, interpretation, writing of the report.

PY - 2018/2

Y1 - 2018/2

N2 - Background: Headache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort.Methods: We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls.Results: We identified 3,343 SNPs which reached the genome-wide significance level of P < 5 x 10-8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92 x 10-47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87 x 10-15 in the LINC02210-CRHR1 gene was the top SNP. Significant relationships between multiple brain tissues and genetic associations were identified through tissue expression analysis. We also identified significant positive genetic correlations between headache and many psychological traits.Conclusions: Our results suggest that brain function is closely related to broadly-defined headache. In addition, we found that many psychological traits have genetic correlations with headache.

AB - Background: Headache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort.Methods: We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls.Results: We identified 3,343 SNPs which reached the genome-wide significance level of P < 5 x 10-8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92 x 10-47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87 x 10-15 in the LINC02210-CRHR1 gene was the top SNP. Significant relationships between multiple brain tissues and genetic associations were identified through tissue expression analysis. We also identified significant positive genetic correlations between headache and many psychological traits.Conclusions: Our results suggest that brain function is closely related to broadly-defined headache. In addition, we found that many psychological traits have genetic correlations with headache.

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KW - Tissue expression

KW - UK biobank

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KW - Genome-Wide Association Study

KW - Humans

KW - Headache/genetics

KW - United Kingdom

KW - Gene Expression Profiling

KW - Genetic Loci

KW - Case-Control Studies

KW - Polymorphism, Single Nucleotide/genetics

KW - Biological Specimen Banks

KW - Linkage Disequilibrium/genetics

KW - Cohort Studies

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DO - 10.1016/j.ebiom.2018.01.023

M3 - Article

VL - 28

SP - 180

EP - 186

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -