{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:15:03Z","timestamp":1792818903602,"version":"4.5.0"},"reference-count":86,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R21NS104398"],"award-info":[{"award-number":["1R21NS104398"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Observational studies have linked migraine to a wide range of risk factors and diseases, although the causality of these associations is uncertain. Mendelian randomization (MR) is an analytic paradigm that exploits germline genetic variants as natural experiments, providing a framework for causal inference from observational data. In this narrative review, we summarize the core principles and assumptions of MR and highlight methodological considerations unique to its application to migraine research. We review key MR findings across several domains of migraine research, noting areas of consistent evidence, as well as conflicting results. We then discuss limitations of MR in the context of migraine research, emphasizing that MR is not a panacea for causal inference. We conclude by underscoring the need for interdisciplinary collaboration between methodologists and domain experts to prioritize patient-relevant questions, refine analytic approaches and translate genetic insights into more effective therapies.<\/jats:p>","DOI":"10.1177\/03331024251414834","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T03:31:38Z","timestamp":1769571098000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Mendelian randomization applied to migraine research: Opportunities and challenges"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-0641","authenticated-orcid":false,"given":"Iyas","family":"Daghlas","sequence":"first","affiliation":[{"name":"University of California San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel I.","family":"Chasman","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30322-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00211-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102414544976"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.wco.0000169750.52406.a2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad363"},{"key":"e_1_3_2_7_2","article-title":"Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study","volume":"357","author":"Hippisley-Cox J","year":"2017","unstructured":"Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. Br Med J 2017; 357: j2099.","journal-title":"Br Med J"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaa016"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2011-200375"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1212321"},{"key":"e_1_3_2_11_2","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies NM","year":"2018","unstructured":"Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. Br Med J 2018; 362: k601.","journal-title":"Br Med J"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyh132"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209128"},{"key":"e_1_3_2_14_2","first-page":"820","article-title":"Serum calcium and risk of migraine: a Mendelian randomization study","volume":"26","author":"Yin P","year":"2016","unstructured":"Yin P, Anttila V, Siewert KM, et al. Serum calcium and risk of migraine: a Mendelian randomization study. Hum Mol Genet 2016; 26: 820\u2013828.","journal-title":"Hum Mol Genet"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03607-5"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21998"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx034"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-018-0424-6"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.652"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.856"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00990-0"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01538-0"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01233-6"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05165-3"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00954-4"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.06.012"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn321"},{"key":"e_1_3_2_33_2","first-page":"96","article-title":"Migraine and risk of cardiovascular diseases: danish population based matched cohort study","volume":"360","author":"Adelborg K","unstructured":"Adelborg K, Sz\u00e9pligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: danish population based matched cohort study. Br Med J 2018 31; 360: 96.","journal-title":"Br Med J"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d0cc8b"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14851"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000653"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14111"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17002-0"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.40577"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201009"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15101"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102411401634"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaa154"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012919"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-023-02532-6"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413485658"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2014.00241"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14470"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200201"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/ane.13528"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420916751"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-024-01801-7"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-024-01956-x"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1401880"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01963-9"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1148458"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-025-02063-7"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac105"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3598"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14101"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13624"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay6690"},{"key":"e_1_3_2_63_2","article-title":"Cerebral small vessel disease genomics and its implications across the lifespan","volume":"11","author":"Sargurupremraj M","unstructured":"Sargurupremraj M, Suzuki H, Jian X, et al. Cerebral small vessel disease genomics and its implications across the lifespan. Nat Commun 11. Epub ahead of print 1 December 2020. DOI: 10.1038\/s41467-020-19111-2.","journal-title":"Nat Commun"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00826-4"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002360"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51228"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.13313"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2025.2504717"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-022-00398-w"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.70398"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02582-z"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.09.011"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1177\/03331024211018131"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011931"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1017\/pcm.2023.5"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.049808"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt179"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010823"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003428"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.3.283"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006650"},{"key":"e_1_3_2_82_2","article-title":"Migraine polygenic risk score associates with efficacy of migraine-specific drugs","volume":"5","author":"Kogelman LJA","unstructured":"Kogelman LJA, Esserlind A-L, Francke Christensen A, et al. Migraine polygenic risk score associates with efficacy of migraine-specific drugs. Neurol Genet 2019 24; 5: e364.","journal-title":"Neurol Genet"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.04.014"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.617472"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004366"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006944"},{"key":"e_1_3_2_87_2","first-page":"1866","article-title":"Triangulation in aetiological epidemiology","volume":"45","author":"Lawlor DA","year":"2016","unstructured":"Lawlor DA, Tilling K, Smith GD. Triangulation in aetiological epidemiology. Int J Epidemiol 2016; 45: 1866\u20131886.","journal-title":"Int J Epidemiol"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024251414834","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03331024251414834","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024251414834","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:44:18Z","timestamp":1777387458000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03331024251414834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":86,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1177\/03331024251414834"],"URL":"https:\/\/doi.org\/10.1177\/03331024251414834","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"03331024251414834"}}