Migraine, chronic kidney disease and kidney function: observational and genetic analyses
Authors: Zhang Wenqiang , Zhang Li , Yang Luo , Xiao Chenghan , Wu Xueyao , Yan Peijing , Cui Huijie , Yang Chao , Zhu Jingwei , Wu Xuan , Tang Mingshuang , Wang Yutong , Chen Lin , Liu Yunjie , Zou Yanqiu , Zhang Ling , Yang Chunxia , Yao Yuqin , Li Jiayuan , Liu Zhenmi , Zhang Ben , Jiang Xia ,   International Headache Genetics Consortium, Anttila Verneri , Artto Ville , Belin Andrea C. , Bjornsdottir Anna , Bjornsdottir Gyda , Boomsma Dorret I. , Børte Sigrid , Chalmer Mona A. , Chasman Daniel I. , Cormand Bru , Cuenca-Leon Ester , Davey-Smith George , de Boer Irene , Dichgans Martin , Esko Tonu , Freilinger Tobias , Gormley Padhraig , Griffiths Lyn R. , Hämäläinen Eija , Hansen Thomas F. , Harder Aster V. E. , Hautakangas Heidi , Hiekkala Marjo , Hrafnsdottir Maria G. , Ikram M. Arfan , Järvelin Marjo-Riitta , Kajanne Risto , Kallela Mikko , Kaprio Jaakko , Kaunisto Mari , Kogelman Lisette J. A. , Kristoffersen Espen S. , Kubisch Christian , Kurki Mitja , Kurth Tobias , Launer Lenore , Lehtimäki Terho , Lessel Davor , Ligthart Lannie , Magnusson Sigurdur H. , Malik Rainer , Müller-Myhsok Bertram , Northover Carrie , Nyholt Dale R. , Olesen Jes , Palotie Aarno , Palta Priit , Pedersen Linda M. , Pedersen Nancy , Pirinen Matti , Posthuma Danielle , Pozo-Rosich Patricia , Pressman Alice , Raitakari Olli , Ran Caroline , Sigurdardottir Gudrun R. , Stefansson Hreinn , Stefansson Kari , Sveinsson Olafur A. , Terwindt Gisela M. , Thorgeirsson Thorgeir E. , van den Maagdenberg Arn M. J. M. , van Duijn Cornelia , Wessman Maija , Winsvold Bendik S. , Zwart John-Anker 
Published: June 2023

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 (Ncase/Ncontrol = 48,975/540,381), CKD (Ncase/Ncontrol = 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.