Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
36705326
TITLE
Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study.
ABSTRACT
OBJECTIVE
To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.
BACKGROUND
To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease. Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition.
METHODS
To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease. Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition. Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.
RESULTS
To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease. Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition. Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed. Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99-1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99-1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96-1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79-1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00-1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92-0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02-1.29, p = 0.025). However, the results were not significant after multiple testing correction.
CONCLUSIONS
To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease. Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition. Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed. Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99-1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99-1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96-1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79-1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00-1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92-0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02-1.29, p = 0.025). However, the results were not significant after multiple testing correction. We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.
© 2023 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.
DATE PUBLISHED
2023 May
HISTORY
PUBSTATUS PUBSTATUSDATE
revised 2022/12/01
received 2022/05/02
accepted 2022/12/05
medline 2023/05/16 06:42
pubmed 2023/01/28 06:00
entrez 2023/01/27 07:53
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Welander NZ Welander Nike Zoe NZ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Rukh G Rukh Gull G Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Rask-Andersen M Rask-Andersen Mathias M Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Harder AVE Harder Aster V E AVE Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
International Headache Genetics Consortium
van den Maagdenberg AMJM van den Maagdenberg Arn M J M AMJM Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Schiöth HB Schiöth Helgi Birgir HB Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Mwinyi J Mwinyi Jessica J Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Gormley Padhraig P
Anttila Verneri V
Winsvold Bendik S BS
Palta Priit P
Esko Tonu T
Pers Tune H TH
Farh Kai-How KH
Cuenca-Leon Ester E
Muona Mikko M
Furlotte Nicholas A NA
Kurth Tobias T
Ingason Andres A
McMahon George G
Ligthart Lannie L
Terwindt Gisela M GM
Kallela Mikko M
Freilinger Tobias M TM
Ran Caroline C
Gordon Scott G SG
Stam Anine H AH
Steinberg Stacy S
Borck Guntram G
Koiranen Markku M
Quaye Lydia L
Adams Hieab H H HHH
Lehtimäki Terho T
Sarin Antti-Pekka AP
Wedenoja Juho J
Hinds David A DA
Buring Julie E JE
Schürks Markus M
Ridker Paul M PM
Hrafnsdottir Maria Gudlaug MG
Stefansson Hreinn H
Ring Susan M SM
Hottenga Jouke-Jan JJ
Penninx Brenda W J H BWJH
Färkkilä Markus M
Artto Ville V
Kaunisto Mari M
Vepsäläinen Salli S
Malik Rainer R
Heath Andrew C AC
Madden Pamela A F PAF
Martin Nicholas G NG
Montgomery Grant W GW
Kurki Mitja M
Kals Mart M
Mägi Reedik R
Pärn Kalle K
Hämäläinen Eija E
Huang Hailiang H
Byrnes Andrea E AE
Franke Lude L
Huang Jie J
Stergiakouli Evie E
Lee Phil H PH
Sandor Cynthia C
Webber Caleb C
Cader Zameel Z
Muller-Myhsok Bertram B
Schreiber Stefan S
Meitinger Thomas T
Eriksson Johan G JG
Salomaa Veikko V
Heikkilä Kauko K
Loehrer Elizabeth E
Uitterlinden Andre G AG
Hofman Albert A
van Duijn Cornelia M CM
Cherkas Lynn L
Pedersen Linda M LM
Stubhaug Audun A
Nielsen Christopher S CS
Männikö Minna M
Mihailov Evelin E
Milani Lili L
Göbel Hartmut H
Esserlind Ann-Louise AL
Christensen Anne Francke AF
Hansen Thomas Folkmann TF
Werge Thomas T
Børte Sigrid S
Cormand Bru B
Eising Else E
Griffiths Lyn L
Hamalainen Eija E
Hiekkala Marjo M
Kajanne Risto R
Launer Lenore L
Lehtimaki Terho T
Lessel Davor D
Macaya Alfons A
Mangino Massimo M
Pedersen Nancy N
Posthuma Danielle D
Pozo-Rosich Patricia P
Pressman Alice A
Sintas Celia C
Vila-Pueyo Marta M
Zhao Huiying H
Kaprio Jaakko J
Aromaa Arpo J AJ
Raitakari Olli O
Ikram M Arfan MA
Spector Tim T
Järvelin Marjo-Riitta MR
Metspalu Andres A
Kubisch Christian C
Strachan David P DP
Ferrari Michel D MD
Belin Andrea C AC
Dichgans Martin M
Wessman Maija M
van den Maagdenberg Arn M J M AMJM
Zwart John-Anker JA
Boomsma Dorret I DI
Smith George Davey GD
Stefansson Kari K
Eriksson Nicholas N
Daly Mark J MJ
Neale Benjamin M BM
Olesen Jes J
Chasman Daniel I DI
Nyholt Dale R DR
Palotie Aarno A
JOURNAL
VOLUME: 63
ISSUE: 5
TITLE: Headache
ISOABBREVIATION: Headache
YEAR: 2023
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1526-4610
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Headache
COUNTRY: United States
ISSNLINKING: 0017-8748
NLMUNIQUEID: 2985091R
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
Åke Wiberg Stiftelse
Marcus Borgströms Stiftelse
SLS-935235 Svenska Läkaresällskapet
SSMF 30072019 Svenska Sällskapet för Medicinsk Forskning
2019-01066 Vetenskapsrådet
Vleugels Stiftelse
GENERAL NOTE
KEYWORDS
KEYWORD
Mendelian randomization
celiac disease
gastrointestinal disease
genetic correlation
inflammatory bowel disease
migraine
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Humans
Colitis, Ulcerative complications
Celiac Disease genetics
Genome-Wide Association Study genetics
Mendelian Randomization Analysis genetics
Migraine without Aura complications
Inflammatory Bowel Diseases genetics
Epilepsy genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's