A genome-wide association study of interhemispheric theta EEG coherence: implications for neural connectivity and alcohol use behavior

Jacquelyn L Meyers; Jian Zhang; David B Chorlian; Ashwini K Pandey; Chella Kamarajan; Jen-Chyong Wang; Leah Wetherill; Dongbing Lai; Michael Chao; Grace Chan; Sivan Kinreich; Manav Kapoor; Sarah Bertelsen; Jeanette McClintick; Lance Bauer; Victor Hesselbrock; Samuel Kuperman; John Kramer; Jessica E Salvatore; Danielle M Dick; Arpana Agrawal; Tatiana Foroud; Howard J Edenberg; Alison Goate; Bernice Porjesz

doi:10.1038/s41380-020-0777-6

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A genome-wide association study of interhemispheric theta EEG coherence: implications for neural connectivity and alcohol use behavior

Journal article

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A genome-wide association study of interhemispheric theta EEG coherence: implications for neural connectivity and alcohol use behavior

Jacquelyn L Meyers, Jian Zhang, David B Chorlian, Ashwini K Pandey, Chella Kamarajan, Jen-Chyong Wang, Leah Wetherill, Dongbing Lai, Michael Chao, Grace Chan, …

Molecular psychiatry, Vol.26(9), pp.5040-5052

09/2021

DOI: 10.1038/s41380-020-0777-6

PMCID: PMC8503860

PMID: 32433515

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https://scholarworks.indianapolis.iu.edu/bitstreams/a54fa5bb-0db3-49ee-84ac-3ab87d7e2a41/downloadView

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Abstract

Aberrant connectivity of large-scale brain networks has been observed among individuals with alcohol use disorders (AUDs) as well as in those at risk, suggesting deficits in neural communication between brain regions in the liability to develop AUD. Electroencephalographical (EEG) coherence, which measures the degree of synchrony between brain regions, may be a useful measure of connectivity patterns in neural networks for studying the genetics of AUD. In 8810 individuals (6644 of European and 2166 of African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Multi-Trait Analyses of genome-wide association studies (MTAG) on parietal resting-state theta (3-7 Hz) EEG coherence, which previously have been associated with AUD. We also examined developmental effects of GWAS findings on trajectories of neural connectivity in a longitudinal subsample of 2316 adolescent/young adult offspring from COGA families (ages 12-30) and examined the functional and clinical significance of GWAS variants. Six correlated single nucleotide polymorphisms located in a brain-expressed lincRNA (ENSG00000266213) on chromosome 18q23 were associated with posterior interhemispheric low theta EEG coherence (3-5 Hz). These same variants were also associated with alcohol use behavior and posterior corpus callosum volume, both in a subset of COGA and in the UK Biobank. Analyses in the subsample of COGA offspring indicated that the association of rs12954372 with low theta EEG coherence occurred only in females, most prominently between ages 25 and 30 (p < 2 × 10 ). Converging data provide support for the role of genetic variants on chromosome 18q23 in regulating neural connectivity and alcohol use behavior, potentially via dysregulated myelination. While findings were less robust, genome-wide associations were also observed with rs151174000 and parieto-frontal low theta coherence, rs14429078 and parieto-occipital interhemispheric high theta coherence, and rs116445911 with centro-parietal low theta coherence. These novel genetic findings highlight the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.

Adolescent

Adult

Alcoholism - genetics

Brain

Child

Electroencephalography

Endophenotypes

Female

Genome-Wide Association Study

Humans

Polymorphism, Single Nucleotide - genetics

Young Adult

Details

Title: Subtitle: A genome-wide association study of interhemispheric theta EEG coherence: implications for neural connectivity and alcohol use behavior
Creators: Jacquelyn L Meyers - SUNY Downstate Health Sciences University
Jian Zhang - SUNY Downstate Health Sciences University
David B Chorlian - SUNY Downstate Health Sciences University
Ashwini K Pandey - SUNY Downstate Health Sciences University
Chella Kamarajan - SUNY Downstate Health Sciences University
Jen-Chyong Wang - Icahn School of Medicine at Mount Sinai
Leah Wetherill - Indiana University
Dongbing Lai - Indiana University
Michael Chao - Icahn School of Medicine at Mount Sinai
Grace Chan - University of Connecticut
Sivan Kinreich - SUNY Downstate Health Sciences University
Manav Kapoor - Icahn School of Medicine at Mount Sinai
Sarah Bertelsen - Icahn School of Medicine at Mount Sinai
Jeanette McClintick - Indiana University
Lance Bauer - University of Connecticut
Victor Hesselbrock - University of Connecticut
Samuel Kuperman - University of Iowa
John Kramer - University of Iowa
Jessica E Salvatore - Virginia Commonwealth University
Danielle M Dick - Virginia Commonwealth University
Arpana Agrawal - Washington University in St. Louis
Tatiana Foroud - Indiana University
Howard J Edenberg - Indiana University
Alison Goate - Icahn School of Medicine at Mount Sinai
Bernice Porjesz - SUNY Downstate Health Sciences University
Resource Type: Journal article
Publication Details: Molecular psychiatry, Vol.26(9), pp.5040-5052
DOI: 10.1038/s41380-020-0777-6
PMID: 32433515
PMCID: PMC8503860
NLM abbreviation: Mol Psychiatry
ISSN: 1359-4184
eISSN: 1476-5578
Grant note: K02 AA018755 / NIAAA NIH HHS K01 DA037914 / NIDA NIH HHS U10 AA008401 / NIAAA NIH HHS K02 DA032573 / NIDA NIH HHS K01 AA024152 / NIAAA NIH HHS
Language: English
Date published: 09/2021
Academic Unit: Psychiatry
Record Identifier: 9984293753402771

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