Genome-wide association study of seasonal affective disorder

Kwo Wei David Ho; Shizhong Han; Jakob V Nielsen; Dubravka Jancic; Benjamin Hing; Jess Fiedorowicz; Myrna M Weissman; Douglas F Levinson; James B Potash

doi:10.1038/s41398-018-0246-z

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Genome-wide association study of seasonal affective disorder

Journal article

Open access

Peer reviewed

Genome-wide association study of seasonal affective disorder

Kwo Wei David Ho, Shizhong Han, Jakob V Nielsen, Dubravka Jancic, Benjamin Hing, Jess Fiedorowicz, Myrna M Weissman, Douglas F Levinson and James B Potash

Translational psychiatry, Vol.8(1), pp.190-8

09/14/2018

DOI: 10.1038/s41398-018-0246-z

PMCID: PMC6138666

PMID: 30217971

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Abstract

Family and twin studies have shown a genetic component to seasonal affective disorder (SAD). A number of candidate gene studies have examined the role of variations within biologically relevant genes in SAD susceptibility, but few genome-wide association studies (GWAS) have been performed to date. The authors aimed to identify genetic risk variants for SAD through GWAS. The authors performed a GWAS for SAD in 1380 cases and 2937 controls of European-American (EA) origin, selected from samples for GWAS of major depressive disorder and of bipolar disorder. Further bioinformatic analyses were conducted to examine additional genomic and biological evidence associated with the top GWAS signals. No susceptibility loci for SAD were identified at a genome-wide significant level. The strongest association was at an intronic variant (rs139459337) within ZBTB20 (odds ratio (OR) = 1.63, p = 8.4 × 10 ), which encodes a transcriptional repressor that has roles in neurogenesis and in adult brain. Expression quantitative trait loci (eQTL) analysis showed that the risk allele "T" of rs139459337 is associated with reduced mRNA expression of ZBTB20 in human temporal cortex (p = 0.028). Zbtb20 is required for normal murine circadian rhythm and for entrainment to a shortened day. Of the 330 human orthologs of murine genes directly repressed by Zbtb20, there were 32 associated with SAD in our sample (at p < 0.05), representing a significant enrichment of ZBTB20 targets among our SAD genetic association signals (fold = 1.93, p = 0.001). ZBTB20 is a candidate susceptibility gene for SAD, based on a convergence of genetic, genomic, and biological evidence. Further studies are necessary to confirm its role in SAD.

European Continental Ancestry Group - genetics

Genetic Predisposition to Disease

Genome-Wide Association Study

United States

Humans

Logistic Models

Male

Transcription Factors - genetics

Bipolar Disorder - genetics

Nerve Tissue Proteins - genetics

Case-Control Studies

Seasonal Affective Disorder - genetics

Depressive Disorder, Major - genetics

Alleles

Female

Polymorphism, Single Nucleotide

Quantitative Trait Loci

Details

Title: Subtitle: Genome-wide association study of seasonal affective disorder
Creators: Kwo Wei David Ho - Department of Neurology, University of Florida, Gainesville, FL, USA
Shizhong Han - Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
Jakob V Nielsen - Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark
Dubravka Jancic - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Benjamin Hing - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Jess Fiedorowicz - Department of Psychiatry, University of Iowa, Iowa City, IA, USA
Myrna M Weissman - The New York State Psychiatric Institute, New York, NY, USA
Douglas F Levinson - Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA, USA
James B Potash - Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. jpotash@jhmi.edu
Resource Type: Journal article
Publication Details: Translational psychiatry, Vol.8(1), pp.190-8
DOI: 10.1038/s41398-018-0246-z
PMID: 30217971
PMCID: PMC6138666
NLM abbreviation: Transl Psychiatry
ISSN: 2158-3188
eISSN: 2158-3188
Publisher: United States
Grant note: R01 MH059535 / NIMH NIH HHS R01 MH060870 / NIMH NIH HHS T32 GM007337 / NIGMS NIH HHS R01 MH061675 / NIMH NIH HHS R01 MH067257 / NIMH NIH HHS R01 MH059566 / NIMH NIH HHS R01 MH060879 / NIMH NIH HHS R01 MH060912 / NIMH NIH HHS R01 MH059548 / NIMH NIH HHS R01 MH061686 / NIMH NIH HHS R01 MH059586 / NIMH NIH HHS R01 MH059567 / NIMH NIH HHS R01 AA022994 / NIAAA NIH HHS R01 MH059587 / NIMH NIH HHS R01 MH059556 / NIMH NIH HHS R01 MH059552 / NIMH NIH HHS Z01 MH002810 / Intramural NIH HHS R01 MH059545 / NIMH NIH HHS R01 MH059533 / NIMH NIH HHS RC2 MH089916 / NIMH NIH HHS R01 MH059588 / NIMH NIH HHS R01 MH059534 / NIMH NIH HHS R01 MH059553 / NIMH NIH HHS R01 MH059565 / NIMH NIH HHS K24 MH064197 / NIMH NIH HHS R01 MH059571 / NIMH NIH HHS R01 MH060068 / NIMH NIH HHS
Language: English
Date published: 09/14/2018
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Epidemiology; Iowa Neuroscience Institute
Record Identifier: 9984065497502771

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