Abstrakti

Epidemiological studies demonstrate an association between migraine and chronic kidney disease (CKD), while the genetic basis underlying the phenotypic association has not been investigated. We aimed to help avoid unnecessary interventions in individuals with migraine through the investigation of phenotypic and genetic relationships underlying migraine, CKD, and kidney function. We first evaluated phenotypic associations using observational data from UK Biobank (N = 255,896). We then investigated genetic relationships leveraging genomic data in European ancestry for migraine (N case/N control = 48,975/540,381), CKD (N case/N control = 41,395/439,303), and two traits of kidney function (estimated glomerular filtration rate [eGFR, N = 567,460] and urinary albumin-to-creatinine ratio [UACR, N = 547,361]). Observational analyses suggested no significant association of migraine with the risk of CKD (HR = 1.13, 95% CI = 0.85–1.50). While we did not find any global genetic correlation in general, we identified four specific genomic regions showing significant for migraine with eGFR. Cross-trait meta-analysis identified one candidate causal variant (rs1047891) underlying migraine, CKD, and kidney function. Transcriptome-wide association study detected 28 shared expression–trait associations between migraine and kidney function. Mendelian randomization analysis suggested no causal effect of migraine on CKD (OR = 1.03, 95% CI = 0.98–1.09; P = 0.28). Despite a putative causal effect of migraine on an increased level of UACR (log-scale-beta = 0.02, 95% CI = 0.01–0.04; P = 1.92 × 10−3), it attenuated to null when accounting for both correlated and uncorrelated pleiotropy. Our work does not find evidence supporting a causal association between migraine and CKD. However, our study highlights significant biological pleiotropy between migraine and kidney function. The value of a migraine prophylactic treatment for reducing future CKD in people with migraine is likely limited.

Alkuperäiskielienglanti
LehtiHuman Genetics
Vuosikerta142
Numero8
Sivut1185-1200
Sivumäärä16
ISSN0340-6717
DOI - pysyväislinkit
TilaJulkaistu - elok. 2023
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Lisätietoja

Funding Information:
We would like to thank the participants and researchers from the International Headache Genetics Consortium who contributed or collected data. We are grateful to the CKDGen Consortium for making the complete meta-GWAS summary statistics publicly available. International Headache Genetics Consortium: Verneri Anttila1,2,3, Ville Artto4, Andrea C Belin5, Anna Bjornsdottir6, Gyda Bjornsdottir7, Dorret I Boomsma8, Sigrid Børte9,10,11, Mona A Chalmer12, Daniel I Chasman13,14, Bru Cormand15, Ester Cuenca-Leon16, George Davey-Smith17, Irene de Boer18, Martin Dichgans19,20, Tonu Esko21, Tobias Freilinger22,23, Padhraig Gormley24, Lyn R Griffiths25, Eija Hämäläinen26, Thomas F Hansen12,27, Aster VE Harder18,28, Heidi Hautakangas26, Marjo Hiekkala29, Maria G Hrafnsdottir30, M. Arfan Ikram31, Marjo-Riitta Järvelin32,33,34,35, Risto Kajanne26, Mikko Kallela4, Jaakko Kaprio26, Mari Kaunisto29, Lisette JA Kogelman12, Espen S Kristoffersen36,37,38, Christian Kubisch39, Mitja Kurki40, Tobias Kurth41, Lenore Launer42, Terho Lehtimäki43, Davor Lessel39, Lannie Ligthart8, Sigurdur H Magnusson7, Rainer Malik19, Bertram Müller-Myhsok44, Carrie Northover45, Dale R Nyholt46, Jes Olesen12, Aarno Palotie26,47, Priit Palta26, Linda M Pedersen48, Nancy Pedersen49, Matti Pirinen26,50,51, Danielle Posthuma52, Patricia Pozo-Rosich53, Alice Pressman54, Olli Raitakari55,56,57, Caroline Ran5, Gudrun R Sigurdardottir6, Hreinn Stefansson7, Kari Stefansson7, Olafur A Sveinsson30, Gisela M Terwindt18, Thorgeir E Thorgeirsson7, Arn MJM van den Maagdenberg18,28, Cornelia van Duijn58, Maija Wessman26,29, Bendik S Winsvold9,48,59, John-Anker Zwart9,10,48.1Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA;2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA;3Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA;4Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland;5Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden;6Neurology private practice, Laeknasetrid, Reykjavik, Iceland;7deCODE genetics/Amgen Inc., Reykjavik, Iceland;8Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands;9K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway;10Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;11Research and Communication Unit for Musculoskeletal Health, Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway;12Danish Headache Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark;13Department of Medicine, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA;14Harvard Medical School, Boston, Massachusetts, USA;15Department of Genetics, Spain Centre for Biomedical Network Research on Rare Diseases, University of Barcelona, Barcelona, Spain;16Pediatric Neurology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain;17University of Bristol/Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK;18Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands;19Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany;20Munich Cluster for Systems Neurology, Munich, Germany;21Estonian Biobank Registry, the Estonian Genome Center, University of Tartu, Tartu, Estonia;22Department of Neurology, Klinikum Passau, Passau, Germany;23Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany;24GSK Inc., Cambridge, Massachusetts, USA;25Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia;26Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland;27Novo Nordic Foundation Center for Protein Research, Copenhagen University, Copenhagen, Denmark;28Department of Human Genetics, Leiden University Medical Centre, Leiden, the Netherlands;29Folkhälsan Research Center, Helsinki, Finland;30Landspitali University Hospital, Reykjavik, Iceland;31Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands;32Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK;33Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland;34Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland;35Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK;36Research and Communication Unit for Musculoskeletal Health, Department of Research, Innovation and Education, Division of Clinical Neuroscience, Akershus University Hospital and University of Oslo, Oslo, Norway;37Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway;38Department of Neurology, Akershus University Hospital, Lørenskog, Norway;39Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;40Psychiatric and Neurodevelopmental Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA;41Institute of Public Health, Charité – Universitätsmedizin, Berlin;42Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA;43Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland;44Max Planck Institute of Psychiatry, Munich, Germany;4523&Me Inc., Mountain View, California, USA;46School of Biomedical Sciences, Faculty of Health, Centre for Genomics and Personalised Health, Centre for Data Science, Queensland University of Technology, Brisbane, Queensland, Australia;47University of Helsinki, Helsinki, Finland;48Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway;49Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;50Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland;51Department of Public Health, University of Helsinki, Helsinki, Finland;52Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands;53Headache Unit, Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain;54Sutter Health, Sacramento, California, USA;55Centre for Population Health Research, University of Turku, Turku University Hospital, Turku, Finland;56Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland;57Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland;58Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, the Netherlands;59Department of Neurology, Oslo University Hospital, Oslo, Norway.

Funding Information:
Open access funding provided by Karolinska Institute. This study was supported by the National Key R&D Program of China (2022YFC3600600, 2022YFC3600604), the National Natural Science Foundation of China (U22A20359, 81874283, 81673255), the Recruitment Program for Young Professionals of China, the Promotion Plan for Basic Medical Sciences and the Development Plan for Cutting-Edge Disciplines, Sichuan University, and other Projects from West China School of Public Health and West China Fourth Hospital, Sichuan University. The sponsors of this study had no role in study design, data collection, analysis, interpretation, writing of the report, or the decision for submission.

Publisher Copyright:
© 2023, The Author(s).

Tieteenalat

  • 3112 Neurotieteet
  • 1184 Genetiikka, kehitysbiologia, fysiologia

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