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Evidence of horizontal indirect genetic effects in humans

Nature Human Behaviour volume 5, pages 399–406 (2021)Cite this article

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Abstract

Indirect genetic effects, the effects of the genotype of one individual on the phenotype of other individuals, are environmental factors associated with human disease and complex trait variation that could help to expand our understanding of the environment linked to complex traits. Here, we study indirect genetic effects in 80,889 human couples of European ancestry for 105 complex traits. Using a linear mixed model approach, we estimate partner indirect heritability and find evidence of partner heritability on ~50% of the analysed traits. Follow-up analysis suggests that in at least ~25% of these traits, the partner heritability is consistent with the existence of indirect genetic effects including a wide variety of traits such as dietary traits, mental health and disease. This shows that the environment linked to complex traits is partially explained by the genotype of other individuals and motivates the need to find new ways of studying the environment.

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Fig. 1: Relationship between direct and indirect genetic effects.
Fig. 2: Difference in IGEs between sexes.
Fig. 3: Evidence of IGEs over the expectation under assortative mating.

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Data availability

The data that support the results presented in this paper can be accessed from UK Biobank after publication. UK Biobank will link the dataset returned to the publication through their application system.

Code availability

The main results of this work were obtained using DISSECT19, which can be freely downloaded from http://www.dissect.ed.ac.uk.

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Acknowledgements

This research has been conducted using the UK Biobank Resource under project 788. The work was funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and an MRC grant (MR/P015514/1). A.T. also acknowledges funding from the Medical Research Council Human Genetic Unit and Health Data Research UK (references HDR-9004 and HDR-9003). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Analyses were performed using the ARCHER UK National Supercomputing Service.

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Authors and Affiliations

  1. The Roslin Institute, The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK

    Charley Xia, Oriol Canela-Xandri, Konrad Rawlik & Albert Tenesa

  2. MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK

    Oriol Canela-Xandri & Albert Tenesa

  3. Usher Institute, Edinburgh bioQuarter, University of Edinburgh, Edinburgh, UK

    Albert Tenesa

Authors
  1. Charley Xia
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  2. Oriol Canela-Xandri
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  3. Konrad Rawlik
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  4. Albert Tenesa
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Contributions

C.X. contributed to the analysis. A.T. designed the study. C.X., O.C.-X., K.R. and A.T. contributed to the interpretation of data and the writing of manuscript.

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Correspondence to Albert Tenesa.

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The authors declare no competing interests.

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

Primary Handling Editor: Stavroula Kousta.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–10, Supplementary Tables 12–21, Supplementary Methods, Supplementary Results and Supplementary References.

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Supplementary Tables 1–11.

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Xia, C., Canela-Xandri, O., Rawlik, K. et al. Evidence of horizontal indirect genetic effects in humans. Nat Hum Behav 5, 399–406 (2021). https://doi.org/10.1038/s41562-020-00991-9

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