AUTHOR=Li Guanglu , Duan Shaojie , International Headache Genetics Consortium (IHGC) , Zheng Tao , Zhu Tiantian , Qu Baoquan , Liu Lei , Liu Zunjing , 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 , Boer Irene de , Dichgans Martin , Esko Tonu , Freilinger Tobias , Gormley Padhraig , Griffiths Lyn R , Hämäläinen Eija , Hansen Thomas F , Harder Aster VE , Hautakangas Heidi , Hiekkala Marjo , Hrafnsdottir Maria G , Ikram M. Arfan , Järvelin Marjo-Riitta , Kajanne Risto , Kallela Mikko , Kaprio Jaakko , Kaunisto Mari , Kogelman Lisette JA , 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 , Maagdenberg Arn MJM vanden , Duijn Cornelia van , Wessman Maija , Winsvold Bendik S , Zwart. John-Anker TITLE=Genetic causal relationship between immune diseases and migraine: a Mendelian randomization study JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1376698 DOI=10.3389/fimmu.2024.1376698 ISSN=1664-3224 ABSTRACT=Background

Migraine has an increased prevalence in several immune disorders, but genetic cause-effect relationships remain unclear. Mendelian randomization (MR) was used in this study to explore whether immune diseases are causally associated with migraine and its subtypes.

Methods

We conducted a two-sample bidirectional multivariate Mendelian randomization study. Single-nucleotide polymorphisms (SNP) for six immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), allergic rhinitis (AR), asthma and psoriasis, were used as genetic instrumental variables. Summary statistics for migraine were obtained from 3 databases: the International Headache Genetics Consortium (IHGC), UK Biobank, and FinnGen study. MR analyses were performed per outcome database for each exposure and subsequently meta-analyzed. Reverse MR analysis was performed to determine whether migraine were risk factors for immune diseases. In addition, we conducted a genetic correlation to identify shared genetic variants for these two associations.

Results

No significant causal relationship was found between immune diseases and migraine and its subtypes. These results were robust with a series of sensitivity analyses. Using the linkage disequilibrium score regression method (LDSC), we detected no genetic correlation between migraine and immune diseases.

Conclusion

The evidence from our study does not support a causal relationship between immune diseases and migraine. The mechanisms underlying the frequent comorbidity of migraine and several immune diseases need to be further elucidated.