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

Author

Onderwater, GLJ, Ligthart, L, Bot, M, Demirkan, A, Fu, J, Van Der Kallen, CJH, Vijfhuizen, LS, Pool, R, Liu, J, Vanmolkot, FHM, Beekman, M, Wen, K-X, Amin, N, Thesing, CS, Pijpers, JA, Kies, DA, Zielman, R, De Boer, I, Van Greevenbroek, MMJ, Arts, ICW, Milaneschi, Y, Schram, MT, Dagnelie, PC, Franke, L, Ikram, MA, Ferrari, MD, Goeman, JJ, Slagboom, PE, Wijmenga, C, Stehouwer, CDA, Boomsma, DI, Van Duijn, CM, Penninx, BW, Hoen, PAC, Terwindt, GM, Van Den Maagdenberg, AMJM, Consortium, Bbmri Metabolomics, Epidemiology, Neurology, Radiology & Nuclear Medicine, Interne Geneeskunde, RS: CARIM - R3 - Vascular biology, MUMC+: MA Alg Interne Geneeskunde (9), Epidemiologie, RS: FHML MaCSBio, RS: FSE MaCSBio, RS: FPN MaCSBio, MUMC+: HVC Pieken Maastricht Studie (9), RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, MUMC+: MA Interne Geneeskunde (3), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: CAPHRI - R5 - Optimising Patient Care, MUMC+: MA Endocrinologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Hematologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Reumatologie (9), APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, APH - Digital Health, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, APH - Personalized Medicine, and APH - Health Behaviors & Chronic Diseases

Subjects
Male, Metabolite, Proton Magnetic Resonance Spectroscopy, Pharmacology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, EPIDEMIOLOGY, 0303 health sciences, biology, GLOBAL TEST, ASSOCIATION, Middle Aged, CARDIOVASCULAR-DISEASE, Meta-analysis, Metabolome, Apolipoprotein A1, Female, Lipoproteins, HDL, Adult, medicine.medical_specialty, Migraine Disorders, BIOMARKERS, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, LIPOPROTEINS, Metabolomics, Sex Factors, SDG 3 - Good Health and Well-being, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, Nuclear Magnetic Resonance, Biomolecular, 030304 developmental biology, Aged, business.industry, medicine.disease, Confidence interval, Endocrinology, chemistry, Migraine, Metabolite profiling, biology.protein, RISK-FACTORS, Neurology (clinical), business, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], 030217 neurology & neurosurgery, Lipoprotein
Abstract

ObjectiveTo identify a plasma metabolomic biomarker signature for migraine.MethodsPlasma 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.ResultsDecreases 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.ConclusionsMetabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.

Published
2019

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