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; Rene 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; 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

doi:10.1212/WNL.0000000000007313

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, Rene 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. ArtsYuri 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-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 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.

Original language	English
Pages (from-to)	E1899-E1911
Number of pages	13
Journal	Neurology
Volume	92
Issue number	16
DOIs	https://doi.org/10.1212/WNL.0000000000007313
Publication status	Published - 16 Apr 2019

Keywords

CARDIOVASCULAR-DISEASE
RISK-FACTORS
GLOBAL TEST
EPIDEMIOLOGY
LIPOPROTEINS
ASSOCIATION
BIOMARKERS

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10.1212/WNL.0000000000007313Licence: CC BY-NC-ND

Cite this

Onderwater, G. L. J., Ligthart, L., Bot, M., Demirkan, A., Fu, J., van der Kallen, C. J. H., Vijfhuizen, L. S., Pool, R., Liu, J., Vanmolkot, F. H. M., Beekman, M., Wen, K., Amin, N., Thesing, C. S., Pijpers, J. A., Kies, D. A., Zielman, R., de Boer, I., van Greevenbroek, M. M. J., ... 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

@article{37202b26822f46dab2dde89caa52f64c,

title = "Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine",

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 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.ResultsDecreases 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.ConclusionsMetabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.",

keywords = "CARDIOVASCULAR-DISEASE, RISK-FACTORS, GLOBAL TEST, EPIDEMIOLOGY, LIPOPROTEINS, ASSOCIATION, BIOMARKERS",

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 Rene Pool and Jun Liu and Vanmolkot, {Floris H. M.} and Marian Beekman and Ke-xin Wen 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 = "Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2019",

month = apr,

day = "16",

doi = "10.1212/WNL.0000000000007313",

language = "English",

volume = "92",

pages = "E1899--E1911",

journal = "Neurology",

issn = "0028-3878",

publisher = "LIPPINCOTT WILLIAMS & 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, K, 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

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, Rene

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

AB - 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 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.ResultsDecreases 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.ConclusionsMetabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.

KW - CARDIOVASCULAR-DISEASE

KW - RISK-FACTORS

KW - GLOBAL TEST

KW - EPIDEMIOLOGY

KW - LIPOPROTEINS

KW - ASSOCIATION

KW - BIOMARKERS

U2 - 10.1212/WNL.0000000000007313

DO - 10.1212/WNL.0000000000007313

M3 - Article

C2 - 30944236

SN - 0028-3878

VL - 92

SP - E1899-E1911

JO - Neurology

JF - Neurology

IS - 16

ER -