Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy

Guy Hindley; Alexey A. Shadrin; Dennis van der Meer; Nadine Parker; Weiqiu Cheng; Kevin S. O'Connell; Shahram Bahrami; Aihua Lin; Naz Karadag; Borge Holen; Thomas Bjella; Ian J. Deary; Gail Davies; W. David Hill; Jan Bressler; Sudha Seshadri; Chun Chieh Fan; Torill Ueland; Srdjan Djurovic; Olav B. Smeland; Oleksandr Frei; Anders M. Dale; Ole A. Andreassen

doi:10.1038/s41562-023-01630-9

Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy

Guy Hindley^*, Alexey A. Shadrin^*, Dennis van der Meer, Nadine Parker, Weiqiu Cheng, Kevin S. O'Connell, Shahram Bahrami, Aihua Lin, Naz Karadag, Borge Holen, Thomas Bjella, Ian J. Deary, Gail Davies, W. David Hill, Jan Bressler, Sudha Seshadri, Chun Chieh Fan, Torill Ueland, Srdjan Djurovic, Olav B. SmelandOleksandr Frei, Anders M. Dale, Ole A. Andreassen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function.Hindley et al. used multivariate statistical genetics tools to examine the genetic underpinnings of cognitive and personality traits and find they are shared across higher order domains of mental functioning.

Original language	English
Pages (from-to)	1584-1600
Number of pages	17
Journal	Nature human behaviour
Volume	7
Issue number	9
Early online date	1 Jun 2023
DOIs	https://doi.org/10.1038/s41562-023-01630-9
Publication status	Published - Sept 2023

Keywords

GENOME-WIDE ASSOCIATION
POLYGENICITY
INTELLIGENCE
NEUROTICISM
REGRESSION
SIGNATURES
DISORDERS
HEALTH

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Cite this

Hindley, G., Shadrin, A. A., van der Meer, D., Parker, N., Cheng, W., O'Connell, K. S., Bahrami, S., Lin, A., Karadag, N., Holen, B., Bjella, T., Deary, I. J., Davies, G., Hill, W. D., Bressler, J., Seshadri, S., Fan, C. C., Ueland, T., Djurovic, S., ... Andreassen, O. A. (2023). Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy. Nature human behaviour, 7(9), 1584-1600. https://doi.org/10.1038/s41562-023-01630-9

@article{61bff417cad94e61ad3a456f3924d772,

title = "Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy",

abstract = "Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function.Hindley et al. used multivariate statistical genetics tools to examine the genetic underpinnings of cognitive and personality traits and find they are shared across higher order domains of mental functioning.",

keywords = "GENOME-WIDE ASSOCIATION, POLYGENICITY, INTELLIGENCE, NEUROTICISM, REGRESSION, SIGNATURES, DISORDERS, HEALTH",

author = "Guy Hindley and Shadrin, {Alexey A.} and {van der Meer}, Dennis and Nadine Parker and Weiqiu Cheng and O'Connell, {Kevin S.} and Shahram Bahrami and Aihua Lin and Naz Karadag and Borge Holen and Thomas Bjella and Deary, {Ian J.} and Gail Davies and Hill, {W. David} and Jan Bressler and Sudha Seshadri and Fan, {Chun Chieh} and Torill Ueland and Srdjan Djurovic and Smeland, {Olav B.} and Oleksandr Frei and Dale, {Anders M.} and Andreassen, {Ole A.}",

year = "2023",

month = sep,

doi = "10.1038/s41562-023-01630-9",

language = "English",

volume = "7",

pages = "1584--1600",

journal = "Nature human behaviour",

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Hindley, G, Shadrin, AA, van der Meer, D, Parker, N, Cheng, W, O'Connell, KS, Bahrami, S, Lin, A, Karadag, N, Holen, B, Bjella, T, Deary, IJ, Davies, G, Hill, WD, Bressler, J, Seshadri, S, Fan, CC, Ueland, T, Djurovic, S, Smeland, OB, Frei, O, Dale, AM & Andreassen, OA 2023, 'Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy', Nature human behaviour, vol. 7, no. 9, pp. 1584-1600. https://doi.org/10.1038/s41562-023-01630-9

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AU - Hindley, Guy

AU - Shadrin, Alexey A.

AU - van der Meer, Dennis

AU - Parker, Nadine

AU - Cheng, Weiqiu

AU - O'Connell, Kevin S.

AU - Bahrami, Shahram

AU - Lin, Aihua

AU - Karadag, Naz

AU - Holen, Borge

AU - Bjella, Thomas

AU - Deary, Ian J.

AU - Davies, Gail

AU - Hill, W. David

AU - Bressler, Jan

AU - Seshadri, Sudha

AU - Fan, Chun Chieh

AU - Ueland, Torill

AU - Djurovic, Srdjan

AU - Smeland, Olav B.

AU - Frei, Oleksandr

AU - Dale, Anders M.

AU - Andreassen, Ole A.

PY - 2023/9

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N2 - Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function.Hindley et al. used multivariate statistical genetics tools to examine the genetic underpinnings of cognitive and personality traits and find they are shared across higher order domains of mental functioning.

AB - Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function.Hindley et al. used multivariate statistical genetics tools to examine the genetic underpinnings of cognitive and personality traits and find they are shared across higher order domains of mental functioning.

KW - GENOME-WIDE ASSOCIATION

KW - POLYGENICITY

KW - INTELLIGENCE

KW - NEUROTICISM

KW - REGRESSION

KW - SIGNATURES

KW - DISORDERS

KW - HEALTH

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DO - 10.1038/s41562-023-01630-9

M3 - Article

C2 - 37365406

SN - 2397-3374

VL - 7

SP - 1584

EP - 1600

JO - Nature human behaviour

JF - Nature human behaviour

IS - 9

ER -