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

BBMRI Metabolomics Consortium

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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
JournalNeurology
Volume92
Issue number16
Early online date3 Apr 2019
DOIs
Publication statusPublished - 16 Apr 2019

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Metabolome
HDL Lipoproteins
Migraine Disorders
Metabolomics
Omega-3 Fatty Acids
Confidence Intervals
Lipoproteins
Lipids
Apolipoprotein A-I
Meta-Analysis
Fatty Acids
Biomarkers
Logistic Models
Cholesterol

Bibliographical note

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

Cite this

BBMRI Metabolomics Consortium. / Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine. In: Neurology. 2019 ; Vol. 92, No. 16. pp. e1899-e1911.
@article{8945e00985cd41dea4057c0c45b87765,
title = "Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine",
abstract = "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.",
author = "Onderwater, {Gerrit L.J.} and Lannie Ligthart and Mariska Bot and Ayse Demirkan and Jingyuan Fu and {van der Kallen}, {Carla J.H.} and Vijfhuizen, {Lisanne S.} and Ren{\'e} Pool and Jun Liu and Vanmolkot, {Floris H.M.} and Marian Beekman and Wen, {Ke Xin} and Najaf Amin and Thesing, {Carisha S.} and Pijpers, {Judith A.} and Kies, {Dennis A.} and Ronald Zielman and {de Boer}, Irene and {van Greevenbroek}, {Marleen M.J.} and Arts, {Ilja C.W.} and Yuri Milaneschi and Schram, {Miranda T.} and Dagnelie, {Pieter C.} and Lude Franke and Ikram, {M. Arfan} and Ferrari, {Michel D.} and Goeman, {Jelle J.} and Slagboom, {P. Eline} and Cisca Wijmenga and Stehouwer, {Coen D.A.} and Boomsma, {Dorret I.} and {van Duijn}, {Cornelia M.} and Penninx, {Brenda W.} and {'t Hoen}, {Peter A.C.} and Terwindt, {Gisela M.} and {van den Maagdenberg}, {Arn M.J.M.} and {BBMRI Metabolomics Consortium}",
note = "Copyright {\circledC} 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.",
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Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine. / BBMRI Metabolomics Consortium.

In: Neurology, Vol. 92, No. 16, 16.04.2019, p. e1899-e1911.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine

AU - Onderwater, Gerrit L.J.

AU - Ligthart, Lannie

AU - Bot, Mariska

AU - Demirkan, Ayse

AU - Fu, Jingyuan

AU - van der Kallen, Carla J.H.

AU - Vijfhuizen, Lisanne S.

AU - Pool, René

AU - Liu, Jun

AU - Vanmolkot, Floris H.M.

AU - Beekman, Marian

AU - Wen, Ke Xin

AU - Amin, Najaf

AU - Thesing, Carisha S.

AU - Pijpers, Judith A.

AU - Kies, Dennis A.

AU - Zielman, Ronald

AU - de Boer, Irene

AU - van Greevenbroek, Marleen M.J.

AU - Arts, Ilja C.W.

AU - Milaneschi, Yuri

AU - Schram, Miranda T.

AU - Dagnelie, Pieter C.

AU - Franke, Lude

AU - Ikram, M. Arfan

AU - Ferrari, Michel D.

AU - Goeman, Jelle J.

AU - Slagboom, P. Eline

AU - Wijmenga, Cisca

AU - Stehouwer, Coen D.A.

AU - Boomsma, Dorret I.

AU - van Duijn, Cornelia M.

AU - Penninx, Brenda W.

AU - 't Hoen, Peter A.C.

AU - Terwindt, Gisela M.

AU - van den Maagdenberg, Arn M.J.M.

AU - BBMRI Metabolomics Consortium

N1 - Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

PY - 2019/4/16

Y1 - 2019/4/16

N2 - 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.

AB - 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.

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U2 - 10.1212/WNL.0000000000007313

DO - 10.1212/WNL.0000000000007313

M3 - Article

VL - 92

SP - e1899-e1911

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 16

ER -