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; Børge 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, Børge 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

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

14 Scopus citations

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.

Original language	English (US)
Journal	Nature Human Behaviour
DOIs	https://doi.org/10.1038/s41562-023-01630-9
State	E-pub ahead of print - Jun 26 2023

Access to Document

10.1038/s41562-023-01630-9

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. Advance online publication. https://doi.org/10.1038/s41562-023-01630-9

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. https://doi.org/10.1038/s41562-023-01630-9

@article{de742e9a9c96421e97e079d826627d43,

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.",

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 B{\o}rge 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}",

note = "{\textcopyright} 2023. The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

month = jun,

day = "26",

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

language = "English (US)",

journal = "Nature Human Behaviour",

issn = "2397-3374",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy

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, Børge

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 - 2023/6/26

Y1 - 2023/6/26

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.

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.

U2 - 10.1038/s41562-023-01630-9

DO - 10.1038/s41562-023-01630-9

M3 - Article

C2 - 37365406

SN - 2397-3374

JO - Nature Human Behaviour

JF - Nature Human Behaviour

ER -

Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy

Abstract

Access to Document

Fingerprint

Cite this