Journal
NEUROLOGY
Volume 92, Issue 16, Pages E1899-E1911Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000007313
Keywords
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Categories
Funding
- BBMRI-NL, a research infrastructure - Dutch government (Netherlands Organization for Scientific Research [NWO] [184.021.007, 184033111]
- Netherlands Organization for the Health Research and Development (ZonMw) [90700217]
- NWO Gravitation Netherlands Organ-on-Chip Initiative [024.003.001]
- VIDI (ZonMw) [91711319]
- NWO VICI [918.56.602]
- Spinoza prize (2009) grants
- Centre for Medical Systems Biology (CMSB) within the Genomics of the Netherlands Initiative (NGI)/NWO
- Netherlands Consortium for Systems Biology (NCSB) within the Genomics of the Netherlands Initiative (NGI)/NWO
- FP7 EU project EUROHEADPAIN [602633]
- Centre for Medical Systems Biology (CMSB) of NGI/NWO
- Netherlands Consortium for Systems Biology (NCSB) of NGI/NWO
- European Network of Genomic and Genetic Epidemiology (ENGAGE) from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant [HEALTH-F4-2007-201413]
- JNPD under the project PERADES [733051021]
- European Union's Horizon 2020 research and innovation programme [667375]
- VENI grant
- CardioVasculair Onderzoek Nederland [CVON 2012-03]
- Erasmus MC University Medical Centre
- NWO
- Netherlands Organisation for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- NGI
- Ministry of Education, Culture and Science
- Ministry of Health, Welfare and Sports
- European Commission (DG XII)
- Erasmus University Rotterdam
- Municipality of Rotterdam
- NWO [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 480-15-001/674, 911-09-032]
- MagW/ZonMW [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 911-09-032]
- Amsterdam Public Health (APH) institute
- Avera Institute, Sioux Falls, South Dakota
- NIH [R01D004215701A, MH081802, 1RC2 MH089951]
- BBRMI-NL [184.033.111]
- Netherlands Twin Registry Repository (NWO Groot) [480-15-001/674]
- Netherlands Twin Registry Repository
- Royal Netherlands Academy of Science Professor Award [PAH/6635]
- Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw) [10-000-1002]
- VU University Medical Center
- GGZ inGeest
- Leiden University Medical Centre
- Leiden University
- GGZ Rivierduinen
- University Medical Centre Groningen
- University of Groningen
- Lentis
- GGZ Friesland
- GGZ Drenthe
- Rob Giel Onderzoekscentrum
- Dutch Government
- Northern Netherlands Collaboration of Provinces (SNN)
- European fund for regional development
- Dutch Ministry of Economic Affairs
- Pieken in de Delta
- Province of Groningen
- Province of Drenthe
- Target project
- University Medical Centre Groningen, the Netherlands
- VIDI (NWO) [864.13.013, 917.14.374]
- Top Institute of Food and Nutrition [TiFN GH0001]
- Stiftelsen Kristian Gerhard Jebsen foundation (Norway)
- RuG investment agenda grant Personalized Health
- European Regional Development Fund [K24DC016312]
- Province of Limburg
- department of Economic Affairs of the Netherlands [310.041]
- Stichting the Weijerhorst
- Pearl String Initiative Diabetes
- Cardiovascular Centre Maastricht
- Cardiovascular Research Institute Maastricht
- School of Nutrition, Toxicology and Metabolism
- Stichting Annadal
- Health Foundation Limburg
- Janssen
- Novo Nordisk
- Sanofi
- BiG Grid, the Dutch e-Science Grid (NWO) [176.010.2005.009]
- ERC advanced grant (FP/2007-2013/ERC grant) [2012322698]
- NWO Spinoza prize [NWO SPI 92-266]
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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 H-1-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 (beta -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) (beta -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 (beta -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.
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