Genomic Architecture of Migraine: A Multi ancestry GWAS Meta analysis of 2.5 Million Participants
- 1Yale Univ. School of Medicine
Abstract
Migraine is a leading cause of disability1, yet preventive treatment remains largely empirical despite the availability of several mechanistically distinct therapies2. Genetic data can clarify mechanisms and therapeutic hypotheses when association signals are integrated with molecular and clinical data3. We meta-analyzed migraine GWAS data from 12 European ancestry cohorts (206,893 cases and 2,093,175 controls) and four African ancestry cohorts (22,115 cases and 178,626 controls). We identified 311 lead variants in European-ancestry analyses and 316 lead variants in trans-ancestry analysis. Fine-mapping and transcriptome-wide analyses prioritized variants and genes implicated in sensory neuronal signaling, vascular tone, and immune regulation, with convergent evidence at several established loci including TRPM8 and PHACTR14. Drug-repurposing analyses identified therapeutic targets and compounds, including established migraine treatments and candidates requiring experimental validation. Genetic correlations, Mendelian randomization, and a phenome-wide scan linked migraine liability to psychiatric, pain, and gastrointestinal phenotypes. Together, these findings expand the known genetic architecture of migraine across ancestries and provide a genetics-led map connecting association signals with biological pathways, multimorbidity and candidate therapeutic mechanisms, providing a foundation for future functional and translational studies.
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BibTeX
@misc{overstreet2026genomic,
title = {{Genomic Architecture of Migraine: A Multi ancestry GWAS Meta analysis of 2.5 Million Participants}},
author = {C. Overstreet and M. Galimberti and K. T. Harsan and S. E. Beck and J. Hirsch and S. Sariya and B. R. Ferolito and Y. Zhou and Y. Zhang and E. I. Weinheimer and A. Lacobelle and Y. Nunez and The VA Million Veteran Program and H. R. Kranzler and J. M. Gaziano and M. Stein and C. Gottschalk and K. W. Choi and A. W. Pereira and J. D. Deak and G. A. Pathak and D. F. Levey and J. Gelernter},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.28.26361638},
url = {https://www.medrxiv.org/content/10.64898/2026.08.28.26361638v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Genomic Architecture of Migraine: A Multi ancestry GWAS Meta analysis of 2.5 Million Participants
AU - C. Overstreet
AU - M. Galimberti
AU - K. T. Harsan
AU - S. E. Beck
AU - J. Hirsch
AU - S. Sariya
AU - B. R. Ferolito
AU - Y. Zhou
AU - Y. Zhang
AU - E. I. Weinheimer
AU - A. Lacobelle
AU - Y. Nunez
AU - The VA Million Veteran Program
AU - H. R. Kranzler
AU - J. M. Gaziano
AU - M. Stein
AU - C. Gottschalk
AU - K. W. Choi
AU - A. W. Pereira
AU - J. D. Deak
AU - G. A. Pathak
AU - D. F. Levey
AU - J. Gelernter
PY - 2026
DA - 2026/08/28
PB - medRxiv
DO - 10.64898/2026.08.28.26361638
UR - https://www.medrxiv.org/content/10.64898/2026.08.28.26361638v1
AB - Migraine is a leading cause of disability1, yet preventive treatment remains largely empirical despite the availability of several mechanistically distinct therapies2. Genetic data can clarify mechanisms and therapeutic hypotheses when association signals are integrated with molecular and clinical data3. We meta-analyzed migraine GWAS data from 12 European ancestry cohorts (206,893 cases and 2,093,175 controls) and four African ancestry cohorts (22,115 cases and 178,626 controls). We identified 311 lead variants in European-ancestry analyses and 316 lead variants in trans-ancestry analysis. Fine-mapping and transcriptome-wide analyses prioritized variants and genes implicated in sensory neuronal signaling, vascular tone, and immune regulation, with convergent evidence at several established loci including TRPM8 and PHACTR14. Drug-repurposing analyses identified therapeutic targets and compounds, including established migraine treatments and candidates requiring experimental validation. Genetic correlations, Mendelian randomization, and a phenome-wide scan linked migraine liability to psychiatric, pain, and gastrointestinal phenotypes. Together, these findings expand the known genetic architecture of migraine across ancestries and provide a genetics-led map connecting association signals with biological pathways, multimorbidity and candidate therapeutic mechanisms, providing a foundation for future functional and translational studies.
ER -