Genetic underpinnings of risky behaviour relate to altered neuroanatomy

BIG BEAR Consortium

doi:10.1038/s41562-020-01027-y

Genetic underpinnings of risky behaviour relate to altered neuroanatomy

BIG BEAR Consortium

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

100 Downloads (Pure)

Abstract

Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving and sexual behaviour in a European sample from the UK Biobank (N = 12,675). We find negative associations between risky behaviour and grey-matter volume in distinct brain regions, including amygdala, ventral striatum, hypothalamus and dorsolateral prefrontal cortex (dlPFC). These effects are replicated in an independent sample recruited from the same population (N = 13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N = 297,025), are inversely associated with grey-matter volume in dlPFC, putamen and hypothalamus. This relation mediates roughly 2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.

Original language	English
Pages (from-to)	787-794
Number of pages	8
Journal	Nature Human Behaviour
Volume	5
Issue number	6
Early online date	28 Jan 2021
DOIs	https://doi.org/10.1038/s41562-020-01027-y
Publication status	Published - Jun 2021

Bibliographical note

Funding Information:
This research was carried out under the auspices of the Brain Imaging and Genetics in Behavioural Research (https://big-bear-research.org/) consortium. We thank N.C. Furtner for helpful comments and D. Manfredi for research assistance. The research was conducted using UKB resources under application no. 40830. The study was supported by funding from an National Science Foundation Early Career Development Program grant (no. 1942917) and The Wharton School Dean’s Research fund to G.N., a European Research Council Consolidator grant to P.D.K. (no. 647648 EdGe), and a European Research Council Consolidator grant (no. 725355 BRAINCODES) and a Swiss National Science Foundation grant (no. 100019L_173248) to C.C.R . R.R.W. was financially supported by NIAAA K23 grant (no. K23 AA023894) and H.R.K. was supported by National Institute of Drug Abuse grant no. P30 DA046345. G.N. thanks C. and R. de la Cruz for ongoing support. The work was carried out on the Dutch national e-infrastructure with the support of the SURF Cooperative. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Data can be accessed via the UK Biobank, and data analysis scripts are available on the Open Science Framework (https://osf.io/qkp4g/).

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Funding

This research was carried out under the auspices of the Brain Imaging and Genetics in Behavioural Research (https://big-bear-research.org/) consortium. We thank N.C. Furtner for helpful comments and D. Manfredi for research assistance. The research was conducted using UKB resources under application no. 40830. The study was supported by funding from an National Science Foundation Early Career Development Program grant (no. 1942917) and The Wharton School Dean’s Research fund to G.N., a European Research Council Consolidator grant to P.D.K. (no. 647648 EdGe), and a European Research Council Consolidator grant (no. 725355 BRAINCODES) and a Swiss National Science Foundation grant (no. 100019L_173248) to C.C.R . R.R.W. was financially supported by NIAAA K23 grant (no. K23 AA023894) and H.R.K. was supported by National Institute of Drug Abuse grant no. P30 DA046345. G.N. thanks C. and R. de la Cruz for ongoing support. The work was carried out on the Dutch national e-infrastructure with the support of the SURF Cooperative. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Data can be accessed via the UK Biobank, and data analysis scripts are available on the Open Science Framework (https://osf.io/qkp4g/).

Funders	Funder number
Wharton School Dean’s Research fund	647648 EdGe
National Science Foundation	1942917
National Institute on Drug Abuse	P30 DA046345
National Institute on Alcohol Abuse and Alcoholism	K23AA023894
Comunidad de Madrid
European Research Council	725355 BRAINCODES
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	100019L_173248

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41562-020-01027-y

Genetic underpinnings of risky behaviour relate to altered neuroanatomyFinal published version, 3.38 MBLicence: Article 25fa Dutch Copyright Act

Persistent URL (handle)

Persistent link

Cite this

@article{4a9fc886a0bf4863bee7823aa28cf4ad,

title = "Genetic underpinnings of risky behaviour relate to altered neuroanatomy",

abstract = "Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving and sexual behaviour in a European sample from the UK Biobank (N = 12,675). We find negative associations between risky behaviour and grey-matter volume in distinct brain regions, including amygdala, ventral striatum, hypothalamus and dorsolateral prefrontal cortex (dlPFC). These effects are replicated in an independent sample recruited from the same population (N = 13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N = 297,025), are inversely associated with grey-matter volume in dlPFC, putamen and hypothalamus. This relation mediates roughly 2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.",

author = "G{\"o}khan Aydogan and Remi Daviet and {Karlsson Linn{\'e}r}, Richard and Hare, {Todd A.} and Kable, {Joseph W.} and Kranzler, {Henry R.} and Wetherill, {Reagan R.} and Ruff, {Christian C.} and Koellinger, {Philipp D.} and Gideon Nave and {BIG BEAR Consortium}",

note = "Funding Information: This research was carried out under the auspices of the Brain Imaging and Genetics in Behavioural Research (https://big-bear-research.org/) consortium. We thank N.C. Furtner for helpful comments and D. Manfredi for research assistance. The research was conducted using UKB resources under application no. 40830. The study was supported by funding from an National Science Foundation Early Career Development Program grant (no. 1942917) and The Wharton School Dean{\textquoteright}s Research fund to G.N., a European Research Council Consolidator grant to P.D.K. (no. 647648 EdGe), and a European Research Council Consolidator grant (no. 725355 BRAINCODES) and a Swiss National Science Foundation grant (no. 100019L_173248) to C.C.R . R.R.W. was financially supported by NIAAA K23 grant (no. K23 AA023894) and H.R.K. was supported by National Institute of Drug Abuse grant no. P30 DA046345. G.N. thanks C. and R. de la Cruz for ongoing support. The work was carried out on the Dutch national e-infrastructure with the support of the SURF Cooperative. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Data can be accessed via the UK Biobank, and data analysis scripts are available on the Open Science Framework (https://osf.io/qkp4g/). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jun,

doi = "10.1038/s41562-020-01027-y",

language = "English",

volume = "5",

pages = "787--794",

journal = "Nature Human Behaviour",

issn = "2397-3374",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Genetic underpinnings of risky behaviour relate to altered neuroanatomy

AU - Aydogan, Gökhan

AU - Daviet, Remi

AU - Karlsson Linnér, Richard

AU - Hare, Todd A.

AU - Kable, Joseph W.

AU - Kranzler, Henry R.

AU - Wetherill, Reagan R.

AU - Ruff, Christian C.

AU - Koellinger, Philipp D.

AU - Nave, Gideon

AU - BIG BEAR Consortium

N1 - Funding Information: This research was carried out under the auspices of the Brain Imaging and Genetics in Behavioural Research (https://big-bear-research.org/) consortium. We thank N.C. Furtner for helpful comments and D. Manfredi for research assistance. The research was conducted using UKB resources under application no. 40830. The study was supported by funding from an National Science Foundation Early Career Development Program grant (no. 1942917) and The Wharton School Dean’s Research fund to G.N., a European Research Council Consolidator grant to P.D.K. (no. 647648 EdGe), and a European Research Council Consolidator grant (no. 725355 BRAINCODES) and a Swiss National Science Foundation grant (no. 100019L_173248) to C.C.R . R.R.W. was financially supported by NIAAA K23 grant (no. K23 AA023894) and H.R.K. was supported by National Institute of Drug Abuse grant no. P30 DA046345. G.N. thanks C. and R. de la Cruz for ongoing support. The work was carried out on the Dutch national e-infrastructure with the support of the SURF Cooperative. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Data can be accessed via the UK Biobank, and data analysis scripts are available on the Open Science Framework (https://osf.io/qkp4g/). Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/6

Y1 - 2021/6

N2 - Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving and sexual behaviour in a European sample from the UK Biobank (N = 12,675). We find negative associations between risky behaviour and grey-matter volume in distinct brain regions, including amygdala, ventral striatum, hypothalamus and dorsolateral prefrontal cortex (dlPFC). These effects are replicated in an independent sample recruited from the same population (N = 13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N = 297,025), are inversely associated with grey-matter volume in dlPFC, putamen and hypothalamus. This relation mediates roughly 2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.

AB - Previous research points to the heritability of risk-taking behaviour. However, evidence on how genetic dispositions are translated into risky behaviour is scarce. Here, we report a genetically informed neuroimaging study of real-world risky behaviour across the domains of drinking, smoking, driving and sexual behaviour in a European sample from the UK Biobank (N = 12,675). We find negative associations between risky behaviour and grey-matter volume in distinct brain regions, including amygdala, ventral striatum, hypothalamus and dorsolateral prefrontal cortex (dlPFC). These effects are replicated in an independent sample recruited from the same population (N = 13,004). Polygenic risk scores for risky behaviour, derived from a genome-wide association study in an independent sample (N = 297,025), are inversely associated with grey-matter volume in dlPFC, putamen and hypothalamus. This relation mediates roughly 2.2% of the association between genes and behaviour. Our results highlight distinct heritable neuroanatomical features as manifestations of the genetic propensity for risk taking.

UR - http://www.scopus.com/inward/record.url?scp=85100558708&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85100558708&partnerID=8YFLogxK

U2 - 10.1038/s41562-020-01027-y

DO - 10.1038/s41562-020-01027-y

M3 - Article

AN - SCOPUS:85100558708

SN - 2397-3374

VL - 5

SP - 787

EP - 794

JO - Nature Human Behaviour

JF - Nature Human Behaviour

IS - 6

ER -

Genetic underpinnings of risky behaviour relate to altered neuroanatomy

Abstract

Bibliographical note

Funding

UN SDGs

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Cite this