Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

Dirk J.A. Smit; Ole A. Andreassen; Dorret I. Boomsma; Scott J. Burwell; David B. Chorlian; Eco J.C. de Geus; Torbjørn Elvsåshagen; Reyna L. Gordon; Jeremy Harper; Ulrich Hegerl; Tilman Hensch; William G. Iacono; Philippe Jawinski; Erik G. Jönsson; Jurjen J. Luykx; Cyrille L. Magne; Stephen M. Malone; Sarah E. Medland; Jacquelyn L. Meyers; Torgeir Moberget; Bernice Porjesz; Christian Sander; Sanjay M. Sisodiya; Paul M. Thompson; Catharina E.M. van Beijsterveldt; Edwin van Dellen; Marc Via; Margaret J. Wright

doi:10.1002/brb3.2188

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

Dirk J.A. Smit^*, Ole A. Andreassen, Dorret I. Boomsma, Scott J. Burwell, David B. Chorlian, Eco J.C. de Geus, Torbjørn Elvsåshagen, Reyna L. Gordon, Jeremy Harper, Ulrich Hegerl, Tilman Hensch, William G. Iacono, Philippe Jawinski, Erik G. Jönsson, Jurjen J. Luykx, Cyrille L. Magne, Stephen M. Malone, Sarah E. Medland, Jacquelyn L. Meyers, Torgeir MobergetBernice Porjesz, Christian Sander, Sanjay M. Sisodiya, Paul M. Thompson, Catharina E.M. van Beijsterveldt, Edwin van Dellen, Marc Via, Margaret J. Wright

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Background and purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. Results: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. Conclusion: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.

Original language	English
Article number	e02188
Pages (from-to)	1-20
Number of pages	20
Journal	Brain and Behavior
Volume	11
Issue number	8
Early online date	21 Jul 2021
DOIs	https://doi.org/10.1002/brb3.2188
Publication status	Published - Aug 2021

Bibliographical note

Funding Information:
D.S. was supported by NWO VENI 451‐08‐026, BBRF (NARSAD) grant 21668, NWO Top 912‐16‐064. O.A.A. reports grants from the Research Council of Norway, the Kristian Gerhard Jebsen Stiftelsen, and South‐Eastern Norway Regional Health Authority. D.I.B. was supported by the KNAW Royal Netherlands Academy of Science Professor Award (PAH/6635), Spinozapremie (NWO‐ 56‐464‐14192), University Research Fellow grant (URF). S.J.B. was funded by T32 DA037183 from the National Institute on Drug Abuse. B.P. and D.B.C. were supported by NIAAA‐AA008401 (awarded to B.P.). T.E. was funded by the South Eastern Norway Regional Health Authority (2015‐078), the Ebbe Frøland Foundation, and a research grant from Mrs. Throne‐Holst. R.L.G. is supported by NIH K18DC017383, NIH DP2HD098859, NSF 1926794. J.H. was funded by T32 DA037183 from the National Institute on Drug Abuse. W.G.I. was supported by grants R37 DA005147, R01 DA036216, R37 AA009367. E.G.J. was supported by the Research Council of Norway. C.L.M. was supported by NSF DGE‐1926736. S.M.M. was supported by R21AA026919. S.E.M was supported by NHMRC APP1158127 and APP1172917. J.L.M. was funded by grant numbers U10 AA008401; K01DA037914. T.M. was supported by the Norwegian Research Council. P.M.T. was funded by NIH grant U54 EB020403 from the Big Data to Knowledge (BD2K) Program. S.M.S was supported by the Epilepsy Society. E.v.D. was supported by the Dutch Organization for Health Research and Development (ZonMW) Grant 60‐63600‐98‐711, and the Brain Center Rudolf Magnus Grant 2019. M.V. was funded by the Ministry of Science and Innovation, Spain, grant number PGC2018‐099013‐A‐I00 and by the María de Maeztu Unit of Excellence (Institute of Neurosciences, Universitat de Barcelona) MDM‐2017‐0729. Brisbane Adolescent Twin Study: Funding was obtained from the Australian Research Council, grant numbers A79600334, A79906588, A79801419, DP0212016. Netherland Twin Register: Funding was obtained from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organisation for Health Research and Development (ZonMW) grants 904‐61‐090, 985‐10‐002, 912‐10‐020, 904‐61‐193,480‐04‐004, 463‐06‐001, 451‐04‐034, 400‐05‐717, Addiction 311‐60‐008, 016‐115‐035, 481‐08‐011, 400‐07‐080, 056‐32‐010, Middelgroot‐911‐09‐032, NWO Gravity program 024.001.003, NWO‐Groot 480‐15‐001/674, Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI‐NL 184.021.007/184.033.111), X‐Omics 184‐034‐019; Amsterdam Public Health research institute (former EMGO+); Neuroscience Amsterdam research institute (former NCA); the European Community's Fifth and Seventh Framework Program (FP5‐LIFE QUALITY‐CT‐2002‐2006, FP7‐HEALTH‐F4‐2007‐2013, grant 01254: GenomEUtwin, grant 01413: ENGAGE and grant 602768: ACTION); the European Research Council Starting 284167, Consolidator 771057, Advanced 230374; Rutgers University Cell and DNA Repository (NIMH U24 MH068457‐06), the National Institutes of Health (NIH, R01D0042157‐01A1, R01MH58799‐03, MH081802, DA018673, R01 DK092127‐04, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995); the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by NWO through grant 2018/EW/00408559, BiG Grid, the Dutch e‐Science Grid and SURFSARA.

Funding Information:
The LIFE cohort (LIFE—Leipzig Research Center for Civilization Diseases) is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by means of the Free State of Saxony within the framework of the excellence initiative.

Funding Information:
T.E. has received speaker's fee from Lundbeck AS. O.A.A. reports personal fees from Lundbeck and from HealthLytix. P.M.T. received a research grant from Biogen, Inc., for work unrelated to this manuscript.

Publisher Copyright:
© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

Funding

D.S. was supported by NWO VENI 451‐08‐026, BBRF (NARSAD) grant 21668, NWO Top 912‐16‐064. O.A.A. reports grants from the Research Council of Norway, the Kristian Gerhard Jebsen Stiftelsen, and South‐Eastern Norway Regional Health Authority. D.I.B. was supported by the KNAW Royal Netherlands Academy of Science Professor Award (PAH/6635), Spinozapremie (NWO‐ 56‐464‐14192), University Research Fellow grant (URF). S.J.B. was funded by T32 DA037183 from the National Institute on Drug Abuse. B.P. and D.B.C. were supported by NIAAA‐AA008401 (awarded to B.P.). T.E. was funded by the South Eastern Norway Regional Health Authority (2015‐078), the Ebbe Frøland Foundation, and a research grant from Mrs. Throne‐Holst. R.L.G. is supported by NIH K18DC017383, NIH DP2HD098859, NSF 1926794. J.H. was funded by T32 DA037183 from the National Institute on Drug Abuse. W.G.I. was supported by grants R37 DA005147, R01 DA036216, R37 AA009367. E.G.J. was supported by the Research Council of Norway. C.L.M. was supported by NSF DGE‐1926736. S.M.M. was supported by R21AA026919. S.E.M was supported by NHMRC APP1158127 and APP1172917. J.L.M. was funded by grant numbers U10 AA008401; K01DA037914. T.M. was supported by the Norwegian Research Council. P.M.T. was funded by NIH grant U54 EB020403 from the Big Data to Knowledge (BD2K) Program. S.M.S was supported by the Epilepsy Society. E.v.D. was supported by the Dutch Organization for Health Research and Development (ZonMW) Grant 60‐63600‐98‐711, and the Brain Center Rudolf Magnus Grant 2019. M.V. was funded by the Ministry of Science and Innovation, Spain, grant number PGC2018‐099013‐A‐I00 and by the María de Maeztu Unit of Excellence (Institute of Neurosciences, Universitat de Barcelona) MDM‐2017‐0729. Brisbane Adolescent Twin Study: Funding was obtained from the Australian Research Council, grant numbers A79600334, A79906588, A79801419, DP0212016. Netherland Twin Register: Funding was obtained from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organisation for Health Research and Development (ZonMW) grants 904‐61‐090, 985‐10‐002, 912‐10‐020, 904‐61‐193,480‐04‐004, 463‐06‐001, 451‐04‐034, 400‐05‐717, Addiction 311‐60‐008, 016‐115‐035, 481‐08‐011, 400‐07‐080, 056‐32‐010, Middelgroot‐911‐09‐032, NWO Gravity program 024.001.003, NWO‐Groot 480‐15‐001/674, Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI‐NL 184.021.007/184.033.111), X‐Omics 184‐034‐019; Amsterdam Public Health research institute (former EMGO+); Neuroscience Amsterdam research institute (former NCA); the European Community's Fifth and Seventh Framework Program (FP5‐LIFE QUALITY‐CT‐2002‐2006, FP7‐HEALTH‐F4‐2007‐2013, grant 01254: GenomEUtwin, grant 01413: ENGAGE and grant 602768: ACTION); the European Research Council Starting 284167, Consolidator 771057, Advanced 230374; Rutgers University Cell and DNA Repository (NIMH U24 MH068457‐06), the National Institutes of Health (NIH, R01D0042157‐01A1, R01MH58799‐03, MH081802, DA018673, R01 DK092127‐04, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995); the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by NWO through grant 2018/EW/00408559, BiG Grid, the Dutch e‐Science Grid and SURFSARA. The LIFE cohort (LIFE—Leipzig Research Center for Civilization Diseases) is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by means of the Free State of Saxony within the framework of the excellence initiative. T.E. has received speaker's fee from Lundbeck AS. O.A.A. reports personal fees from Lundbeck and from HealthLytix. P.M.T. received a research grant from Biogen, Inc., for work unrelated to this manuscript.

Funders	Funder number
Amsterdam Public Health Research Institute
Avera Institute for Human Genetics	2018/EW/00408559
Biobanking and Biomolecular Resources Research Infrastructure	BBMRI‐NL 184.021.007/184.033.111
Biogen, Inc.
Dutch Organization for Health Research and Development
ENGAGE	602768
Ebbe Frøland foundation	K18DC017383, DP2HD098859
European Community's Fifth and Seventh Framework Program	FP5‐LIFE QUALITY‐CT‐2002‐2006, 01254, 01413, FP7‐HEALTH‐F4‐2007‐2013
Koninklijke Nederlandse Akademie van Wetenschappen	PAH/6635, T32 DA037183, 56‐464‐14192
NBIC/BioAssist/RK	2008.024
NIAAA‐AA008401
Neuroscience Amsterdam research institute
SURFsara
National Science Foundation	R37 DA005147, R37 AA009367, R01 DA036216, R21AA026919, 1926794, DGE‐1926736
National Institutes of Health	1RC2 MH089951, 1RC2 MH089995, DA018673, R01D0042157‐01A1, R01MH58799‐03, R01 DK092127‐04, MH081802
National Institute of Mental Health	U24 MH068457‐06, R01MH058799
National Institute on Drug Abuse
Brain and Behavior Research Foundation
National Alliance for Research on Schizophrenia and Depression	Top 912‐16‐064, 21668
European Commission
European Research Council
Australian Research Council	DP0212016, A79600334, A79801419, A79906588
National Health and Medical Research Council	APP1172917, U10 AA008401, K01DA037914, APP1158127
ZonMw	480‐15‐001/674, 904‐61‐090, 400‐05‐717, 016‐115‐035, 024.001.003, 985‐10‐002, 056‐32‐010, 451‐04‐034, 463‐06‐001, 481‐08‐011, 60‐63600‐98‐711, 904‐61‐193,480‐04‐004, 400‐07‐080, 912‐10‐020
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	VENI 451‐08‐026
Ministerio de Ciencia e Innovación	PGC2018‐099013‐A‐I00
Norges forskningsråd	U54 EB020403
Universitat de Barcelona	MDM‐2017‐0729
Helse Sør-Øst RHF	2015‐078
European Regional Development Fund
Centre for Medical Systems Biology
Epilepsy Society

Keywords

brain disorders
electroencephalography
ENIGMA
harmonization
imaging genetics
open science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/brb3.2188

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Cite this

Smit, D. J. A., Andreassen, O. A., Boomsma, D. I., Burwell, S. J., Chorlian, D. B., de Geus, E. J. C., Elvsåshagen, T., Gordon, R. L., Harper, J., Hegerl, U., Hensch, T., Iacono, W. G., Jawinski, P., Jönsson, E. G., Luykx, J. J., Magne, C. L., Malone, S. M., Medland, S. E., Meyers, J. L., ... Wright, M. J. (2021). Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity. Brain and Behavior, 11(8), 1-20. Article e02188. https://doi.org/10.1002/brb3.2188

@article{e5d3239430c74f3c9f7381c06659a5eb,

title = "Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity",

abstract = "Background and purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. Results: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. Conclusion: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.",

keywords = "brain disorders, electroencephalography, ENIGMA, harmonization, imaging genetics, open science",

author = "Smit, {Dirk J.A.} and Andreassen, {Ole A.} and Boomsma, {Dorret I.} and Burwell, {Scott J.} and Chorlian, {David B.} and {de Geus}, {Eco J.C.} and Torbj{\o}rn Elvs{\aa}shagen and Gordon, {Reyna L.} and Jeremy Harper and Ulrich Hegerl and Tilman Hensch and Iacono, {William G.} and Philippe Jawinski and J{\"o}nsson, {Erik G.} and Luykx, {Jurjen J.} and Magne, {Cyrille L.} and Malone, {Stephen M.} and Medland, {Sarah E.} and Meyers, {Jacquelyn L.} and Torgeir Moberget and Bernice Porjesz and Christian Sander and Sisodiya, {Sanjay M.} and Thompson, {Paul M.} and {van Beijsterveldt}, {Catharina E.M.} and {van Dellen}, Edwin and Marc Via and Wright, {Margaret J.}",

note = "Funding Information: D.S. was supported by NWO VENI 451‐08‐026, BBRF (NARSAD) grant 21668, NWO Top 912‐16‐064. O.A.A. reports grants from the Research Council of Norway, the Kristian Gerhard Jebsen Stiftelsen, and South‐Eastern Norway Regional Health Authority. D.I.B. was supported by the KNAW Royal Netherlands Academy of Science Professor Award (PAH/6635), Spinozapremie (NWO‐ 56‐464‐14192), University Research Fellow grant (URF). S.J.B. was funded by T32 DA037183 from the National Institute on Drug Abuse. B.P. and D.B.C. were supported by NIAAA‐AA008401 (awarded to B.P.). T.E. was funded by the South Eastern Norway Regional Health Authority (2015‐078), the Ebbe Fr{\o}land Foundation, and a research grant from Mrs. Throne‐Holst. R.L.G. is supported by NIH K18DC017383, NIH DP2HD098859, NSF 1926794. J.H. was funded by T32 DA037183 from the National Institute on Drug Abuse. W.G.I. was supported by grants R37 DA005147, R01 DA036216, R37 AA009367. E.G.J. was supported by the Research Council of Norway. C.L.M. was supported by NSF DGE‐1926736. S.M.M. was supported by R21AA026919. S.E.M was supported by NHMRC APP1158127 and APP1172917. J.L.M. was funded by grant numbers U10 AA008401; K01DA037914. T.M. was supported by the Norwegian Research Council. P.M.T. was funded by NIH grant U54 EB020403 from the Big Data to Knowledge (BD2K) Program. S.M.S was supported by the Epilepsy Society. E.v.D. was supported by the Dutch Organization for Health Research and Development (ZonMW) Grant 60‐63600‐98‐711, and the Brain Center Rudolf Magnus Grant 2019. M.V. was funded by the Ministry of Science and Innovation, Spain, grant number PGC2018‐099013‐A‐I00 and by the Mar{\'i}a de Maeztu Unit of Excellence (Institute of Neurosciences, Universitat de Barcelona) MDM‐2017‐0729. Brisbane Adolescent Twin Study: Funding was obtained from the Australian Research Council, grant numbers A79600334, A79906588, A79801419, DP0212016. Netherland Twin Register: Funding was obtained from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organisation for Health Research and Development (ZonMW) grants 904‐61‐090, 985‐10‐002, 912‐10‐020, 904‐61‐193,480‐04‐004, 463‐06‐001, 451‐04‐034, 400‐05‐717, Addiction 311‐60‐008, 016‐115‐035, 481‐08‐011, 400‐07‐080, 056‐32‐010, Middelgroot‐911‐09‐032, NWO Gravity program 024.001.003, NWO‐Groot 480‐15‐001/674, Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI‐NL 184.021.007/184.033.111), X‐Omics 184‐034‐019; Amsterdam Public Health research institute (former EMGO+); Neuroscience Amsterdam research institute (former NCA); the European Community's Fifth and Seventh Framework Program (FP5‐LIFE QUALITY‐CT‐2002‐2006, FP7‐HEALTH‐F4‐2007‐2013, grant 01254: GenomEUtwin, grant 01413: ENGAGE and grant 602768: ACTION); the European Research Council Starting 284167, Consolidator 771057, Advanced 230374; Rutgers University Cell and DNA Repository (NIMH U24 MH068457‐06), the National Institutes of Health (NIH, R01D0042157‐01A1, R01MH58799‐03, MH081802, DA018673, R01 DK092127‐04, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995); the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by NWO through grant 2018/EW/00408559, BiG Grid, the Dutch e‐Science Grid and SURFSARA. Funding Information: The LIFE cohort (LIFE—Leipzig Research Center for Civilization Diseases) is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by means of the Free State of Saxony within the framework of the excellence initiative. Funding Information: T.E. has received speaker's fee from Lundbeck AS. O.A.A. reports personal fees from Lundbeck and from HealthLytix. P.M.T. received a research grant from Biogen, Inc., for work unrelated to this manuscript. Publisher Copyright: {\textcopyright} 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.",

year = "2021",

month = aug,

doi = "10.1002/brb3.2188",

language = "English",

volume = "11",

pages = "1--20",

journal = "Brain and Behavior",

issn = "2162-3279",

publisher = "John Wiley and Sons Inc.",

number = "8",

}

Smit, DJA, Andreassen, OA, Boomsma, DI, Burwell, SJ, Chorlian, DB, de Geus, EJC, Elvsåshagen, T, Gordon, RL, Harper, J, Hegerl, U, Hensch, T, Iacono, WG, Jawinski, P, Jönsson, EG, Luykx, JJ, Magne, CL, Malone, SM, Medland, SE, Meyers, JL, Moberget, T, Porjesz, B, Sander, C, Sisodiya, SM, Thompson, PM, van Beijsterveldt, CEM, van Dellen, E, Via, M & Wright, MJ 2021, 'Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity', Brain and Behavior, vol. 11, no. 8, e02188, pp. 1-20. https://doi.org/10.1002/brb3.2188

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity. / Smit, Dirk J.A.; Andreassen, Ole A.; Boomsma, Dorret I. et al.
In: Brain and Behavior, Vol. 11, No. 8, e02188, 08.2021, p. 1-20.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Large-scale collaboration in ENIGMA-EEG

T2 - A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

AU - Smit, Dirk J.A.

AU - Andreassen, Ole A.

AU - Boomsma, Dorret I.

AU - Burwell, Scott J.

AU - Chorlian, David B.

AU - de Geus, Eco J.C.

AU - Elvsåshagen, Torbjørn

AU - Gordon, Reyna L.

AU - Harper, Jeremy

AU - Hegerl, Ulrich

AU - Hensch, Tilman

AU - Iacono, William G.

AU - Jawinski, Philippe

AU - Jönsson, Erik G.

AU - Luykx, Jurjen J.

AU - Magne, Cyrille L.

AU - Malone, Stephen M.

AU - Medland, Sarah E.

AU - Meyers, Jacquelyn L.

AU - Moberget, Torgeir

AU - Porjesz, Bernice

AU - Sander, Christian

AU - Sisodiya, Sanjay M.

AU - Thompson, Paul M.

AU - van Beijsterveldt, Catharina E.M.

AU - van Dellen, Edwin

AU - Via, Marc

AU - Wright, Margaret J.

N1 - Funding Information: D.S. was supported by NWO VENI 451‐08‐026, BBRF (NARSAD) grant 21668, NWO Top 912‐16‐064. O.A.A. reports grants from the Research Council of Norway, the Kristian Gerhard Jebsen Stiftelsen, and South‐Eastern Norway Regional Health Authority. D.I.B. was supported by the KNAW Royal Netherlands Academy of Science Professor Award (PAH/6635), Spinozapremie (NWO‐ 56‐464‐14192), University Research Fellow grant (URF). S.J.B. was funded by T32 DA037183 from the National Institute on Drug Abuse. B.P. and D.B.C. were supported by NIAAA‐AA008401 (awarded to B.P.). T.E. was funded by the South Eastern Norway Regional Health Authority (2015‐078), the Ebbe Frøland Foundation, and a research grant from Mrs. Throne‐Holst. R.L.G. is supported by NIH K18DC017383, NIH DP2HD098859, NSF 1926794. J.H. was funded by T32 DA037183 from the National Institute on Drug Abuse. W.G.I. was supported by grants R37 DA005147, R01 DA036216, R37 AA009367. E.G.J. was supported by the Research Council of Norway. C.L.M. was supported by NSF DGE‐1926736. S.M.M. was supported by R21AA026919. S.E.M was supported by NHMRC APP1158127 and APP1172917. J.L.M. was funded by grant numbers U10 AA008401; K01DA037914. T.M. was supported by the Norwegian Research Council. P.M.T. was funded by NIH grant U54 EB020403 from the Big Data to Knowledge (BD2K) Program. S.M.S was supported by the Epilepsy Society. E.v.D. was supported by the Dutch Organization for Health Research and Development (ZonMW) Grant 60‐63600‐98‐711, and the Brain Center Rudolf Magnus Grant 2019. M.V. was funded by the Ministry of Science and Innovation, Spain, grant number PGC2018‐099013‐A‐I00 and by the María de Maeztu Unit of Excellence (Institute of Neurosciences, Universitat de Barcelona) MDM‐2017‐0729. Brisbane Adolescent Twin Study: Funding was obtained from the Australian Research Council, grant numbers A79600334, A79906588, A79801419, DP0212016. Netherland Twin Register: Funding was obtained from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organisation for Health Research and Development (ZonMW) grants 904‐61‐090, 985‐10‐002, 912‐10‐020, 904‐61‐193,480‐04‐004, 463‐06‐001, 451‐04‐034, 400‐05‐717, Addiction 311‐60‐008, 016‐115‐035, 481‐08‐011, 400‐07‐080, 056‐32‐010, Middelgroot‐911‐09‐032, NWO Gravity program 024.001.003, NWO‐Groot 480‐15‐001/674, Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI‐NL 184.021.007/184.033.111), X‐Omics 184‐034‐019; Amsterdam Public Health research institute (former EMGO+); Neuroscience Amsterdam research institute (former NCA); the European Community's Fifth and Seventh Framework Program (FP5‐LIFE QUALITY‐CT‐2002‐2006, FP7‐HEALTH‐F4‐2007‐2013, grant 01254: GenomEUtwin, grant 01413: ENGAGE and grant 602768: ACTION); the European Research Council Starting 284167, Consolidator 771057, Advanced 230374; Rutgers University Cell and DNA Repository (NIMH U24 MH068457‐06), the National Institutes of Health (NIH, R01D0042157‐01A1, R01MH58799‐03, MH081802, DA018673, R01 DK092127‐04, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995); the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by NWO through grant 2018/EW/00408559, BiG Grid, the Dutch e‐Science Grid and SURFSARA. Funding Information: The LIFE cohort (LIFE—Leipzig Research Center for Civilization Diseases) is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by means of the Free State of Saxony within the framework of the excellence initiative. Funding Information: T.E. has received speaker's fee from Lundbeck AS. O.A.A. reports personal fees from Lundbeck and from HealthLytix. P.M.T. received a research grant from Biogen, Inc., for work unrelated to this manuscript. Publisher Copyright: © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

PY - 2021/8

Y1 - 2021/8

N2 - Background and purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. Results: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. Conclusion: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.

AB - Background and purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. Results: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. Conclusion: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.

KW - brain disorders

KW - electroencephalography

KW - ENIGMA

KW - harmonization

KW - imaging genetics

KW - open science

UR - http://www.scopus.com/inward/record.url?scp=85110990235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85110990235&partnerID=8YFLogxK

U2 - 10.1002/brb3.2188

DO - 10.1002/brb3.2188

M3 - Article

C2 - 34291596

AN - SCOPUS:85110990235

SN - 2162-3279

VL - 11

SP - 1

EP - 20

JO - Brain and Behavior

JF - Brain and Behavior

IS - 8

M1 - e02188

ER -

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

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