Genetic Correlation Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multi-Site Study of Multiplex Pedigrees

Emma E M Knowles; Juan Manuel Peralta; Laura Almasy; Vishwajit Nimgaonkar; Francis J. McMahon; Andrew M. McIntosh; Pippa Thomson; Samuel Mathias; Ruben C. Gur; Joanne E. Curran; Henriette Raventós; Javier  Contreras; Assen Jablensky; Jo Badcock; John Blangero; Raquel E. Gur; David C. Glahn

doi:10.1016/j.biopsych.2021.03.012

Genetic Correlation Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multi-Site Study of Multiplex Pedigrees

Emma E M Knowles, Juan Manuel Peralta, Laura Almasy, Vishwajit Nimgaonkar, Francis J. McMahon, Andrew M. McIntosh, Pippa Thomson, Samuel Mathias, Ruben C. Gur, Joanne E. Curran, Henriette Raventós, Javier Contreras, Assen Jablensky, Jo Badcock, John Blangero, Raquel E. Gur, David C. Glahn

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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 four 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.
Findings. 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 depression was characterized by enhanced Working and Face Memory performance, as reflected in significant genetic overlap in two samples.
Interpretation. 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, tend to be specific to ascertainment strategy, ethnicity, and cognitive test battery.

Original language	English
Pages (from-to)	373-384
Number of pages	12
Journal	Biological Psychiatry
Volume	90
Issue number	6
Early online date	17 Mar 2021
DOIs	https://doi.org/10.1016/j.biopsych.2021.03.012
Publication status	Published - 15 Sept 2021

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10.1016/j.biopsych.2021.03.012

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403107/

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

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title = "Genetic Correlation Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multi-Site Study of Multiplex Pedigrees",

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 four 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.Findings. 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 depression was characterized by enhanced Working and Face Memory performance, as reflected in significant genetic overlap in two samples.Interpretation. 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, tend to be specific to ascertainment strategy, ethnicity, and cognitive test battery.",

author = "Knowles, {Emma E M} and Peralta, {Juan Manuel} and Laura Almasy and Vishwajit Nimgaonkar and McMahon, {Francis J.} and McIntosh, {Andrew M.} and Pippa Thomson and Samuel Mathias and Gur, {Ruben C.} and Curran, {Joanne E.} and Henriette Ravent{\'o}s and Javier Contreras and Assen Jablensky and Jo Badcock and John Blangero and Gur, {Raquel E.} and Glahn, {David C.}",

year = "2021",

month = sep,

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doi = "10.1016/j.biopsych.2021.03.012",

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Knowles, EEM, Peralta, JM, Almasy, L, Nimgaonkar, V, McMahon, FJ, McIntosh, AM, Thomson, P, Mathias, S, Gur, RC, Curran, JE, Raventós, H, Contreras, J, Jablensky, A, Badcock, J, Blangero, J, Gur, RE & Glahn, DC 2021, 'Genetic Correlation Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multi-Site Study of Multiplex Pedigrees', Biological Psychiatry, vol. 90, no. 6, pp. 373-384. https://doi.org/10.1016/j.biopsych.2021.03.012

TY - JOUR

T1 - Genetic Correlation Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multi-Site Study of Multiplex Pedigrees

AU - Knowles, Emma E M

AU - Peralta, Juan Manuel

AU - Almasy, Laura

AU - Nimgaonkar, Vishwajit

AU - McMahon, Francis J.

AU - McIntosh, Andrew M.

AU - Thomson, Pippa

AU - Mathias, Samuel

AU - Gur, Ruben C.

AU - Curran, Joanne E.

AU - Raventós, Henriette

AU - Contreras, Javier

AU - Jablensky, Assen

AU - Badcock, Jo

AU - Blangero, John

AU - Gur, Raquel E.

AU - Glahn, David C.

PY - 2021/9/15

Y1 - 2021/9/15

N2 - 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 four 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.Findings. 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 depression was characterized by enhanced Working and Face Memory performance, as reflected in significant genetic overlap in two samples.Interpretation. 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, tend to be specific to ascertainment strategy, ethnicity, and cognitive test battery.

AB - 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 four 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.Findings. 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 depression was characterized by enhanced Working and Face Memory performance, as reflected in significant genetic overlap in two samples.Interpretation. 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, tend to be specific to ascertainment strategy, ethnicity, and cognitive test battery.

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DO - 10.1016/j.biopsych.2021.03.012

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C2 - 33975707

SN - 0006-3223

VL - 90

SP - 373

EP - 384

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 6

ER -

Genetic Correlation Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multi-Site Study of Multiplex Pedigrees

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