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Meta-Analysis
. 2021 Sep 15;90(6):373-384.
doi: 10.1016/j.biopsych.2021.03.012. Epub 2021 Mar 17.

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

Emma E M Knowles  1 , Juan M Peralta  2 , Laura Almasy  3 , Vishwajit Nimgaonkar  4 , Francis J McMahon  5 , Andrew M McIntosh  6 , Pippa Thomson  7 , Samuel R Mathias  8 , Ruben C Gur  9 , Joanne E Curran  2 , Henriette Raventós  10 , Javier Contreras  11 , Assen Jablensky  12 , Johanna Badcock  13 , John Blangero  2 , Raquel E Gur  9 , David C Glahn  14
Affiliations
Meta-Analysis

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

Emma E M Knowles et al. Biol Psychiatry. .

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.

Keywords: Bipolar disorder; Cognition; Family-based genetics; Genetic epidemiology; Major depressive disorder; Psychotic disorders.

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Conflict of interest statement

Declaration of Interests

The authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1.
Figure 1.
mERV β estimates for psychosis (CR = Costa Rican; MA = Mexican American; PA = Pennsylvanian; WA = Western Australian).
Figure 2.
Figure 2.
Genetic overlap (or ERV) profiles for psychosis (*significant after multiple testing correction; CR = Costa Rican; MA = Mexican American; PA = Pennsylvanian; WA = Western Australian).
Figure 3.
Figure 3.
mERV β estimates for bipolar (BP) and major depressive (MD) disorders (CR = Costa Rican; MA = Mexican American; PA = Pennsylvanian; WA = Western Australian).
Figure 4.
Figure 4.
Genetic overlap (or ERV) profiles for bipolar (BP) and major depressive (MD) disorders (*significant after multiple testing correction; CR = Costa Rican; MA = Mexican American; PA = Pennsylvanian; WA = Western Australian).
Figure 5.
Figure 5.
Genetic overlap (or ERV) profiles for major depressive disorder (*significant after multiple testing correction; CR = Costa Rican; MA = Mexican American; PA = Pennsylvanian; WA = Western Australian).
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