SEARCHCOHORTneurology, nephrology

cohort·neurology, nephrology, epidemiology, internal medicine, preclinical research·PMC10449948

Migraine, chronic kidney disease and kidney function: observational and genetic analyses

Human Genetics · 22 authors, 7 centres

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TL;DR

This study used observational and genetic methods to investigate the relationship between migraine and chronic kidney disease (CKD) or kidney function. It found no strong evidence supporting a causal effect of migraine on CKD, but identified shared genetic pathways linking migraine to kidney function measures.

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The study conducted a comprehensive observational and genetic analysis using large-scale human data of European ancestry. Observational analyses from a cohort found a minimal phenotypic link between migraine and CKD, with a hazard ratio of 1.32 (95% CI = 1.07–1.61) that attenuated to null after full adjustment. Genetic analyses, including Mendelian randomization, found no significant genetic correlation or causal association between migraine and CKD. However, evidence supported a shared genetic architecture between migraine and continuous kidney function measures like eGFR, identifying pleiotropic loci such as rs1047891 near CPS1 and shared expression-trait associations. Limitations include the focus on European ancestry, potential sample overlap, and restricted analysis to overall migraine without subtypes. The findings suggest migraine does not appear to cause CKD, but highlight biological pleiotropy that may inform future research and prevention strategies.

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cohort

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neurology

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ORIGINAL PAPER

PMC10449948

Migraine, chronic kidney disease and kidney function: observational and genetic analyses

Human Genetics

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ABSTRACT

Abstract 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. Supplementary Information The online version contains supplementary material available at 10.1007/s00439-023-02575-9.

CITATION EXPORT

Wenqiang Zhang, Li Zhang, Luo Yang et al.. Migraine, chronic kidney disease and kidney function: observational and genetic analyses. Human Genetics. (2023). https://doi.org/10.1007/s00439-023-02575-9

AUTHORS

22 · 7 CENTRES

Wenqiang Zhang, Li Zhang, Luo Yang, Chenghan Xiao, Xueyao Wu, Peijing Yan, Huijie Cui, Chao Yang, Jingwei Zhu, Xuan Wu, Mingshuang Tang, Yutong Wang, Lin Chen, Yunjie Liu, Yanqiu Zou, Ling Zhang, Chunxia Yang, Yuqin Yao, Jiayuan Li, Zhenmi Liu, Ben Zhang, Xia Jiang

1Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041 China
2Department of Urology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
3Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
4Department of Iatrical Polymer Material and Artificial Apparatus, School of Polymer Science and Engineering, Sichuan University, Chengdu, China
5Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
6Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
7Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden