Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2020 Apr;183(3):181-194.
doi: 10.1002/ajmg.b.32775. Epub 2019 Dec 24.

Genome-wide association study of cognitive performance in U.S. veterans with schizophrenia or bipolar disorder

Philip D Harvey  1   2 , Ning Sun  3   4 , Tim B Bigdeli  5   6 , Ayman H Fanous  5   6 , Mihaela Aslan  3   4 , Anil K Malhotra  7   8   9 , Qiongshi Lu  4   10 , Yiming Hu  4 , Boyang Li  4 , Quan Chen  3   4 , Shrikant Mane  4 , Perry Miller  3   4 , Nallakkandi Rajeevan  3   4 , Frederick Sayward  3   4 , Kei-Hoi Cheung  3   4 , Yuli Li  3   4 , Tiffany A Greenwood  11 , Raquel E Gur  12   13 , David L Braff  11   14 ; Consortium on the Genetics of Schizophrenia (COGS); Mary Brophy  15   16 , Saiju Pyarajan  15 , Timothy J O'Leary  17 , Theresa Gleason  17 , Ronald Przygodszki  17 , Sumitra Muralidhar  17 , J Michael Gaziano  15   18 , John Concato  3   4 , Hongyu Zhao  3   4 , Larry J Siever  19   20
Affiliations
Multicenter Study

Genome-wide association study of cognitive performance in U.S. veterans with schizophrenia or bipolar disorder

Philip D Harvey et al. Am J Med Genet B Neuropsychiatr Genet. 2020 Apr.

Abstract

Cognitive impairment is a frequent and serious problem in patients with various forms of severe mental illnesses (SMI), including schizophrenia (SZ) and bipolar disorder (BP). Recent research suggests genetic links to several cognitive phenotypes in both SMI and in the general population. Our goal in this study was to identify potential genomic signatures of cognitive functioning in veterans with severe mental illness and compare them to previous findings for cognition across different populations. Veterans Affairs (VA) Cooperative Studies Program (CSP) Study #572 evaluated cognitive and functional capacity measures among SZ and BP patients. In conjunction with the VA Million Veteran Program, 3,959 European American (1,095 SZ, 2,864 BP) and 2,601 African American (1,095 SZ, 2,864 BP) patients were genotyped using a custom Affymetrix Axiom Biobank array. We performed a genome-wide association study of global cognitive functioning, constructed polygenic scores for SZ and cognition in the general population, and examined genetic correlations with 2,626 UK Biobank traits. Although no single locus attained genome-wide significance, observed allelic effects were strongly consistent with previous studies. We observed robust associations between global cognitive functioning and polygenic scores for cognitive performance, intelligence, and SZ risk. We also identified significant genetic correlations with several cognition-related traits in UK Biobank. In a diverse cohort of U.S. veterans with SZ or BP, we demonstrate broad overlap of common genetic effects on cognition in the general population, and find that greater polygenic loading for SZ risk is associated with poorer cognitive performance.

Keywords: bipolar disorder; cognition; genome-wide association study (GWAS); impairment; schizophrenia.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. 1000 Genomes Project Consortium, Auton, A., Brooks, L. D., Durbin, R. M., Garrison, E. P., Kang, H. M., … Abecasis, G. R. (2015). A global reference for human genetic variation. Nature, 526(7571), 68-74.
    1. Abraham, G., & Inouye, M. (2014). Fast principal component analysis of large-scale genome-wide data. PLoS One, 9(4), e93766.
    1. American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders, fourth edition, text revision (DSM-IV-TR) (Vol. 1, 4th ed.). Arlington, VA: American Psychiatric Association.
    1. Bora, E., Yucel, M., & Pantelis, C. (2009). Cognitive endophenotypes of bipolar disorder: A meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. Journal of Affective Disorders, 113, 1-20. https://doi.org/10.1016/j.jad.2008.06.009
    1. Bowie, C. R., Depp, C., McGrath, J. A., Wolyniec, P., Mausbach, B. T., Thornquist, M. H., … Pulver, A. E. (2010). Prediction of real-world functional disability in chronic mental disorders: A comparison of schizophrenia and bipolar disorder. The American Journal of Psychiatry, 167(9), 1116-1124.

Publication types

MeSH terms

  NODES
admin 2
Association 13
COMMUNITY 1
Idea 1
idea 1
INTERN 1
Project 1
twitter 2