Association and genetic overlap between clinical chemistry tests and migraine

The International Headache Genetics Consortium (IHGC)

doi:10.1177/03331024211018131

Association and genetic overlap between clinical chemistry tests and migraine

The International Headache Genetics Consortium (IHGC)

Queensland University of Technology QUT
QIMR Berghofer Medical Research Institute
Massachusetts General Hospital
Broad Institute of MIT and Harvard
Wellcome Trust
University of Oslo
University of Helsinki
Estonian Biocentre
Boston Children's Hospital
Statens Serum Institut
University of Copenhagen
Illumina Inc.
Universitat Autònoma de Barcelona
Folkh€alsan Institute of Genetics
23andMe Inc.
Institute for Radiology, CCM
Brigham and Women's Hospital
deCODE Genetics
University of Bristol
VU Amsterdam
LUMC Leiden University Medical Center
HUCH Comprehensive Cancer Center
Hertie-Institut fur klinische Hirnforschung
Ludwig Maximilian University of Munich
Karolinska Institute
University of Ulm
Oulun Yliopisto
King's College London
Erasmus University Medical Center
University of Tampere
Harvard Medical School
University Hospital Essen
Landspitali University Hospital
VU University Hospital
Washington University School of Medicine in St. Louis
Institute of Biological Psychiatry
Medical and Population Genetics Program

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

13 Citations (Scopus)

Abstract

Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10⁻⁴ < p < 3 × 10⁻²). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

Original language	English
Pages (from-to)	1208-1221
Number of pages	14
Journal	Cephalalgia
Volume	41
Issue number	11-12
DOIs	https://doi.org/10.1177/03331024211018131
Publication status	Published - Oct 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Biochemistry tests
gene-based genetic overlap
genetic correlation
Mendelian randomisation
SNP-based genetic overlap

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10.1177/03331024211018131

Cite this

@article{e4e69f9c55ac42bb8522779c7af57684,

title = "Association and genetic overlap between clinical chemistry tests and migraine",

abstract = "Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10−4 < p < 3 × 10−2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.",

keywords = "Biochemistry tests, gene-based genetic overlap, genetic correlation, Mendelian randomisation, SNP-based genetic overlap",

author = "Tanha, \{Hamzeh M.\} and Martin, \{Nicholas G.\} and Whitfield, \{John B.\} and Nyholt, \{Dale R.\} and Padhraig Gormley and Verneri Anttila and Winsvold, \{Bendik S.\} and Priit Palta and Tonu Esko and Pers, \{Tune H.\} and Farh, \{Kai How\} and Ester Cuenca-Leon and Mikko Muona and Furlotte, \{Nicholas A.\} and Tobias Kurth and Andres Ingason and George McMahon and Lannie Ligthart and Terwindt, \{Gisela M.\} and Mikko Kallela and Freilinger, \{Tobias M.\} and Caroline Ran and Gordon, \{Scott G.\} and Stam, \{Anine H.\} and Stacy Steinberg and Guntram Borck and Markku Koiranen and Lydia Quaye and Adams, \{Hieab H.H.\} and Terho Lehtim€aki and Sarin, \{Antti Pekka\} and Juho Wedenoja and Hinds, \{David A.\} and Buring, \{Julie E.\} and Markus Schurks and Ridker, \{Paul M.\} and Hrafnsdottir, \{Maria Gudlaug\} and Hreinn Stefansson and Ring, \{Susan M.\} and Hottenga, \{Jouke Jan\} and Penninx, \{Brenda WJH\} and Markus F€arkkil€a and Ville Artto and Mari Kaunisto and Salli Veps€al€ainen and Rainer Malik and Madden, \{Pamela AF\} and Hansen, \{Thomas Folkmann\} and Tim Spector and Neale, \{Benjamin M.\} and \{The International Headache Genetics Consortium (IHGC)\}",

note = "Publisher Copyright: {\textcopyright} International Headache Society 2021.",

year = "2021",

month = oct,

doi = "10.1177/03331024211018131",

language = "English",

volume = "41",

pages = "1208--1221",

journal = "Cephalalgia",

issn = "0333-1024",

publisher = "SAGE Publications Ltd",

number = "11-12",

}

TY - JOUR

T1 - Association and genetic overlap between clinical chemistry tests and migraine

AU - Tanha, Hamzeh M.

AU - Martin, Nicholas G.

AU - Whitfield, John B.

AU - Nyholt, Dale R.

AU - Gormley, Padhraig

AU - Anttila, Verneri

AU - Winsvold, Bendik S.

AU - Palta, Priit

AU - Esko, Tonu

AU - Pers, Tune H.

AU - Farh, Kai How

AU - Cuenca-Leon, Ester

AU - Muona, Mikko

AU - Furlotte, Nicholas A.

AU - Kurth, Tobias

AU - Ingason, Andres

AU - McMahon, George

AU - Ligthart, Lannie

AU - Terwindt, Gisela M.

AU - Kallela, Mikko

AU - Freilinger, Tobias M.

AU - Ran, Caroline

AU - Gordon, Scott G.

AU - Stam, Anine H.

AU - Steinberg, Stacy

AU - Borck, Guntram

AU - Koiranen, Markku

AU - Quaye, Lydia

AU - Adams, Hieab H.H.

AU - Lehtim€aki, Terho

AU - Sarin, Antti Pekka

AU - Wedenoja, Juho

AU - Hinds, David A.

AU - Buring, Julie E.

AU - Schurks, Markus

AU - Ridker, Paul M.

AU - Hrafnsdottir, Maria Gudlaug

AU - Stefansson, Hreinn

AU - Ring, Susan M.

AU - Hottenga, Jouke Jan

AU - Penninx, Brenda WJH

AU - F€arkkil€a, Markus

AU - Artto, Ville

AU - Kaunisto, Mari

AU - Veps€al€ainen, Salli

AU - Malik, Rainer

AU - Madden, Pamela AF

AU - Hansen, Thomas Folkmann

AU - Spector, Tim

AU - Neale, Benjamin M.

AU - The International Headache Genetics Consortium (IHGC)

PY - 2021/10

Y1 - 2021/10

N2 - Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10−4 < p < 3 × 10−2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

AB - Introduction: In this paper, we studied several serum clinical chemistry tests of cardiovascular disease (CVD), iron deficiency anemia, liver and kidney disorders in migraine. Methods: We first explored the association of 22 clinical chemistry tests with migraine risk in 697 migraine patients and 2722 controls. To validate and interpret association findings, cross-trait genetic analyses were conducted utilising genome-wide association study (GWAS) data comprising 23,986 to 452,264 individuals. Results: Significant associations with migraine risk were identified for biomarkers of CVD risk, iron deficiency and liver dysfunction (odds ratios = 0.86–1.21; 1 × 10−4 < p < 3 × 10−2). Results from cross-trait genetic analyses corroborate the significant biomarker associations and indicate their relationship with migraine is more consistent with biological pleiotropy than causality. For example, association and genetic overlap between a lower level of HDL-C and increased migraine risk are due to shared biology rather than a causal relationship. Furthermore, additional genetic analyses revealed shared genetics among migraine, the clinical chemistry tests, and heart problems and iron deficiency anemia, but not liver disease. Conclusions: These findings highlight common biological mechanisms underlying migraine, heart problems and iron deficiency anemia and provide support for their investigation in the development of novel therapeutic and dietary interventions.

KW - Biochemistry tests

KW - gene-based genetic overlap

KW - genetic correlation

KW - Mendelian randomisation

KW - SNP-based genetic overlap

UR - https://www.scopus.com/pages/publications/85117387254

U2 - 10.1177/03331024211018131

DO - 10.1177/03331024211018131

M3 - Article

C2 - 34130515

AN - SCOPUS:85117387254

SN - 0333-1024

VL - 41

SP - 1208

EP - 1221

JO - Cephalalgia

JF - Cephalalgia

IS - 11-12

ER -

Association and genetic overlap between clinical chemistry tests and migraine

Abstract

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Keywords

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