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

Gerrit L.J. Onderwater, Lannie Ligthart, Mariska Bot, Ayse Demirkan, Jingyuan Fu, Carla J.H. van der Kallen, Lisanne S. Vijfhuizen, René Pool, Jun Liu, Floris H.M. Vanmolkot, Marian Beekman, Ke Xin Wen, Najaf Amin, Carisha S. Thesing, Judith A. Pijpers, Dennis A. Kies, Ronald Zielman, Irene de Boer, Marleen M.J. van Greevenbroek, Ilja C.W. Arts & 17 others Yuri Milaneschi, Miranda T. Schram, Pieter C. Dagnelie, Lude Franke, M. Arfan Ikram, Michel D. Ferrari, Jelle J. Goeman, P. Eline Slagboom, Cisca Wijmenga, Coen D.A. Stehouwer, Dorret I. Boomsma, Cornelia M. van Duijn, Brenda W. Penninx, Peter A.C. 't Hoen, Gisela M. Terwindt, Arn M.J.M. van den Maagdenberg, 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
JournalNeurology
Volume92
Issue number16
DOIs
Publication statusPublished - 16 Apr 2019

Cite this

Onderwater, G. L. J., Ligthart, L., Bot, M., Demirkan, A., Fu, J., van der Kallen, C. J. H., ... BBMRI Metabolomics Consortium (2019). Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine. Neurology, 92(16), e1899-e1911. https://doi.org/10.1212/WNL.0000000000007313
Onderwater, Gerrit L.J. ; Ligthart, Lannie ; Bot, Mariska ; Demirkan, Ayse ; Fu, Jingyuan ; van der Kallen, Carla J.H. ; Vijfhuizen, Lisanne S. ; Pool, René ; Liu, Jun ; Vanmolkot, Floris H.M. ; Beekman, Marian ; Wen, Ke Xin ; Amin, Najaf ; Thesing, Carisha S. ; Pijpers, Judith A. ; Kies, Dennis A. ; Zielman, Ronald ; de Boer, Irene ; van Greevenbroek, Marleen M.J. ; Arts, Ilja C.W. ; Milaneschi, Yuri ; Schram, Miranda T. ; Dagnelie, Pieter C. ; Franke, Lude ; Ikram, M. Arfan ; Ferrari, Michel D. ; Goeman, Jelle J. ; Slagboom, P. Eline ; Wijmenga, Cisca ; Stehouwer, Coen D.A. ; Boomsma, Dorret I. ; van Duijn, Cornelia M. ; Penninx, Brenda W. ; 't Hoen, Peter A.C. ; Terwindt, Gisela M. ; van den Maagdenberg, Arn M.J.M. ; 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{48953a020c164791bff18b7c4a803a10,
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}",
year = "2019",
month = "4",
day = "16",
doi = "10.1212/WNL.0000000000007313",
language = "English",
volume = "92",
pages = "e1899--e1911",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "16",

}

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, KX, 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, 't Hoen, PAC, Terwindt, GM, van den Maagdenberg, AMJM & BBMRI Metabolomics Consortium 2019, 'Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine' Neurology, vol. 92, no. 16, pp. e1899-e1911. https://doi.org/10.1212/WNL.0000000000007313

Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine. / Onderwater, Gerrit L.J.; Ligthart, Lannie; Bot, Mariska; Demirkan, Ayse; Fu, Jingyuan; van der Kallen, Carla J.H.; Vijfhuizen, Lisanne S.; Pool, René; Liu, Jun; Vanmolkot, Floris H.M.; Beekman, Marian; Wen, Ke Xin; Amin, Najaf; Thesing, Carisha S.; Pijpers, Judith A.; Kies, Dennis A.; Zielman, Ronald; de Boer, Irene; van Greevenbroek, Marleen M.J.; Arts, Ilja C.W.; Milaneschi, Yuri; Schram, Miranda T.; Dagnelie, Pieter C.; Franke, Lude; Ikram, M. Arfan; Ferrari, Michel D.; Goeman, Jelle J.; Slagboom, P. Eline; Wijmenga, Cisca; Stehouwer, Coen D.A.; Boomsma, Dorret I.; van Duijn, Cornelia M.; Penninx, Brenda W.; 't Hoen, Peter A.C.; Terwindt, Gisela M.; van den Maagdenberg, Arn M.J.M.; 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

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.

UR - http://www.scopus.com/inward/record.url?scp=85064760662&partnerID=8YFLogxK

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 -

Onderwater GLJ, Ligthart L, Bot M, Demirkan A, Fu J, van der Kallen CJH et al. Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine. Neurology. 2019 Apr 16;92(16):e1899-e1911. https://doi.org/10.1212/WNL.0000000000007313