Genetic Overlap Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multisite Study of Multiplex Pedigrees

Authors

Emma Knowles
Juan M. Peralta, The University of Texas Rio Grande Valley
Laura Almasy, The University of Texas Rio Grande Valley
Vishwajit Nimgaonkar
Francis J. McMahon
Pippa Thomson
Samuel R. Mathias
Joanne E. Curran, The University of Texas Rio Grande Valley
John Blangero, The University of Texas Rio Grande Valley

Document Type

Article

Publication Date

9-15-2021

Abstract

Background: Cognitive impairment is a key feature of psychiatric illness, making cognition an important tool for exploring of the genetics of illness risk. It remains unclear which measures should be prioritized in pleiotropy-guided research. Here, we generate profiles of genetic overlap between psychotic and affective disorders and cognitive measures in Caucasian and Hispanic groups.

Methods: Data were from 4 samples of extended pedigrees (N = 3046). Coefficient of relationship analyses were used to estimate genetic overlap between illness risk and cognitive ability. Results were meta-analyzed.

Results: Psychosis was characterized by cognitive impairments on all measures with a generalized profile of genetic overlap. General cognitive ability shared greatest genetic overlap with psychosis risk (average endophenotype ranking value [ERV] across samples from a random-effects meta-analysis = 0.32), followed by verbal memory (ERV = 0.24), executive function (ERV = 0.22), and working memory (ERV = 0.21). For bipolar disorder, there was genetic overlap with processing speed (ERV = 0.05) and verbal memory (ERV = 0.11), but these were confined to select samples. Major depressive disorder was characterized by enhanced working and face memory performance, as reflected in significant genetic overlap in 2 samples.

Conclusions: There is substantial genetic overlap between risk for psychosis and a range of cognitive abilities (including general intelligence). Most of these effects are largely stable across of ascertainment strategy and ethnicity. Genetic overlap between affective disorders and cognition, on the other hand, tends to be specific to ascertainment strategy, ethnicity, and cognitive test battery.

Comments

© 2021 Society of Biological Psychiatry. All rights reserved. Original published version available at https://doi.org/10.1016/j.biopsych.2021.03.012

Recommended Citation

Knowles, E., Peralta, J. M., Almasy, L., Nimgaonkar, V., McMahon, F. J., McIntosh, A. M., Thomson, P., Mathias, S. R., Gur, R. C., Curran, J. E., Raventós, H., Contreras, J., Jablensky, A., Badcock, J., Blangero, J., Gur, R. E., & Glahn, D. C. (2021). Genetic Overlap Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multisite Study of Multiplex Pedigrees. Biological psychiatry, 90(6), 373–384. https://doi.org/10.1016/j.biopsych.2021.03.012

Publication Title

Biological psychiatry

DOI

10.1016/j.biopsych.2021.03.012

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics