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

  • 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.
Author:Dirk J. A. SmitORCiD, Ole A. AndreassenORCiD, Dorret BoomsmaORCiDGND, Scott J. BurwellORCiD, David B. ChorlianORCiD, Eco J. C. de GeusORCiD, Torbjørn ElvsåshagenORCiDGND, Reyna L. GordonORCiD, Jeremy HarperORCiD, Ulrich HegerlORCiDGND, Tilman HenschORCiDGND, William G. IaconoORCiD, Philippe JawinskiORCiDGND, Erik G. JönssonORCiD, Jurjen J. LuykxORCiD, Cyrille L. MagneORCiD, Stephen M. Malone, Sarah E. MedlandORCiD, Jacquelyn L. MeyersORCiD, Torgeir MobergetORCiDGND, Bernice PorjeszORCiD, Christian SanderORCiDGND, Sanjay M. SisodiyaORCiD, Paul M. ThompsonORCiD, Catharina Eugenie Maria van BeijsterveldtGND, Edwin van DellenORCiD, Marc ViaORCiD, Margaret J. WrightORCiD
Parent Title (English):Brain and behavior
Place of publication:Malden, Mass.
Document Type:Article
Date of Publication (online):2021/07/21
Date of first Publication:2021/07/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/07/11
Tag:ENIGMA; brain disorders; electroencephalography; harmonization; imaging genetics; open science
Issue:8, art. e02188
Page Number:20
First Page:1
Last Page:20
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.
Dewey Decimal Classification:1 Philosophie und Psychologie / 15 Psychologie / 150 Psychologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0