Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine

BBMRI Metabolomics Consortium

Research output: Contribution to JournalArticleAcademicpeer-review


OBJECTIVE: To identify a plasma metabolomic biomarker signature for migraine.

METHODS: Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses.

RESULTS: Decreases in the level of apolipoprotein A1 (β -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (β -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (β -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status.

CONCLUSIONS: Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.

Original languageEnglish
Pages (from-to)e1899-e1911
Number of pages13
Issue number16
Early online date3 Apr 2019
Publication statusPublished - 16 Apr 2019

Bibliographical note

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.


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    Onderwater, G. L. J. (Contributor), Ligthart, L. (Contributor), Bot, M. (Contributor), Demirkan, A. (Contributor), Fu, J. (Contributor), Van Der Kallen, C. J. H. (Contributor), Vijfhuizen, L. S. (Contributor), Pool, R. (Contributor), Liu, J. (Contributor), Vanmolkot, F. H. M. (Contributor), Beekman, M. (Contributor), Wen, H. (Contributor), Amin, N. (Contributor), Thesing, C. S. (Contributor), Pijpers, J. A. (Contributor), Kies, D. A. (Contributor), Zielman, R. (Contributor), De Boer, I. (Contributor), Van Greevenbroek, M. M. J. (Contributor), Arts, I. C. W. (Contributor), Milaneschi, Y. (Contributor), Schram, M. T. (Contributor), Dagnelie, P. C. (Contributor), Franke, L. (Contributor), Ikram, M. A. (Contributor), Ferrari, M. D. (Contributor), Goeman, J. J. (Contributor), Slagboom, P. E. (Contributor), Wijmenga, C. (Contributor), Stehouwer, C. D. A. (Contributor), Boomsma, D. (Contributor), Van Duijn, C. M. (Contributor), Penninx, B. W. (Contributor), ’T Hoen, P. A. C. (Contributor), Terwindt, G. M. (Contributor) & Van Den Maagdenberg, A. M. J. M. (Contributor), Unknown Publisher, 1 Jan 2019


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