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Direct and Indirect Effects of Maternal, Paternal, and Offspring Genotypes: Trio-GCTA

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Abstract

Indirect genetic effects from relatives may result in misleading quantifications of heritability, but can also be of interest in their own right. In this paper we propose Trio-GCTA, a model for separating direct and indirect genetic effects when genome-wide single nucleotide polymorphism data have been collected from parent-offspring trios. The model is applicable to phenotypes obtained from any of the family members. We discuss appropriate parameter interpretations and apply the method to three exemplar phenotypes: offspring birth weight, maternal relationship satisfaction, and paternal body-mass index, using real data from the Norwegian Mother, Father and Child Cohort Study (MoBa).

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Code availability

Code for estimating the model is available at https://github.com/espenmei/trio

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Acknowledgements

The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this on-going cohort study. This publication is a part of the project “Intergenerational Transmission of Internalizing and Externalizing Psychopathological Spectra: A Genome-Wide Complex Trait Study” supported by the Research Council of Norway (262177). Espen Moen Eilertsen and Eivind Ystrom was supported by the Norwegian Research Council (262177 and 288083). Laurie Hannigan was supported by a grant from the South-Eastern Norway Regional Health Authority (2018059). Alexandra Havdahl was supported by the South-Eastern Norway Regional Health Authority (2018058 and 2020022). Tom A. McAdams was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (107706/Z/15/Z) and the Norwegian Research Council (288083). Eshim S. Jami was supported by the European Union’s Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions (721567). This work was partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. This research is part of the HARVEST collaboration, supported by the Research Council of Norway (229624). We further thank the Center for Diabetes Research, the University of Bergen for providing genotype data and performing quality control and imputation of the data funded by the ERC AdG project SELECTionPREDISPOSED, Stiftelsen Kristian Gerhard Jebsen, Trond Mohn Foundation, the Research Council of Norway, the Novo Nordisk Foundation, the University of Bergen, and the Western Norway health Authorities (Helse Vest).

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Authors and Affiliations

  1. Department of Psychology, University of Oslo, Forskningsveien 3A, 0373, Oslo, Norway

    Espen Moen Eilertsen, Alexandra S. Havdahl & Eivind Ystrom

  2. Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Eshim Shahid Jami

  3. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College, London, UK

    Tom A. McAdams

  4. Nic Waals Institute, Lovisenberg Diakonale Hospital, Oslo, Norway

    Laurie J. Hannigan & Alexandra S. Havdahl

  5. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    Alexandra S. Havdahl & David M. Evans

  6. Department of Psychology, PROMENTA Research Center, University of Oslo, Oslo, Norway

    Espen Moen Eilertsen, Tom A. McAdams, Alexandra S. Havdahl & Eivind Ystrom

  7. University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia

    David M. Evans

  8. PharmacoEpidemiology and Drug Safety Research Group, School of Pharmacy, University of Oslo, Oslo, Norway

    Eivind Ystrom

  9. Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway

    Espen Moen Eilertsen & Per Magnus

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  1. Espen Moen Eilertsen
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Correspondence to Espen Moen Eilertsen.

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Conflict of interest

Espen Moen Eilertsen, Eshim Shahid Jami, Tom A. McAdams, Laurie J. Hannigan, Alexandra S. Havdahl, Per Magnus, David M. Evans, and Eivind Ystrom declare that they have no conflict of interest.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Regional Committee for Medical Research Ethics.

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Eilertsen, E.M., Jami, E.S., McAdams, T.A. et al. Direct and Indirect Effects of Maternal, Paternal, and Offspring Genotypes: Trio-GCTA. Behav Genet 51, 154–161 (2021). https://doi.org/10.1007/s10519-020-10036-6

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