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Dissecting polygenic signals from genome-wide association studies on human behaviour

Abstract

Genome-wide association studies on human behavioural traits are producing large amounts of polygenic signals with significant predictive power and potentially useful biological clues. Behavioural traits are more distal and are less directly under biological control compared with physical characteristics, which makes the associated genetic effects harder to interpret. The results of genome-wide association studies for human behaviour are likely made up of a composite of signals from different sources. While sample sizes continue to increase, we outline additional steps that need to be taken to better delineate the origin of the increasingly stronger polygenic signals. In addition to genetic effects on the traits themselves, the major sources of polygenic signals are those that are associated with correlated traits, environmental effects and ascertainment bias. Advances in statistical approaches that disentangle polygenic effects from different traits as well as extending data collection to families and social circles with better geographical coverage will probably contribute to filling the gap of knowledge between genetic effects and behavioural outcomes.

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Fig. 1: The complexity of the associations between DNA sequence variants and human behaviour.
Fig. 2: Genetic correlations, SNP-based heritabilities and twin/family-based heritabilities.

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Acknowledgements

A.A. and K.J.H.V. are supported by the Foundation Volksbond Rotterdam. A.A. is also supported by ZonMw grant no. 849200011 from The Netherlands Organisation for Health Research and Development.

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Correspondence to Abdel Abdellaoui.

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Peer review information Nature Human Behaviour thanks Anders Børglum and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Table 1: the numerical values of heritability estimates from Fig. 2, as well as the references for the twin/family studies and GWASs that Fig. 2 is based on.

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Abdellaoui, A., Verweij, K.J.H. Dissecting polygenic signals from genome-wide association studies on human behaviour. Nat Hum Behav 5, 686–694 (2021). https://doi.org/10.1038/s41562-021-01110-y

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