Genetic underpinnings of risky behaviour relate to altered neuroanatomy

BIG BEAR Consortium

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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 languageEnglish
JournalNature Human Behaviour
DOIs
Publication statusAccepted/In press - 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.

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