Abstract
Maternal depressive symptoms are highly prevalent and can negatively impact affected individuals and family members. Understanding etiological influences on maternal depression, such as genetic liability, is key to inform treatment and prevention efforts. Here we quantified direct and indirect genetic effects (that is, when genetic variants in other individuals influence risk of maternal depression through the environment) from partners and offspring on maternal depressive symptoms at multiple time points using genome-wide complex trait analysis with parent–offspring trios. We used data from the Norwegian Mother, Father and Child cohort study, including up to 21,000 genotyped parent–offspring trios. Models with indirect genetic effects had best fit at three out of five time points (3, 5 and 8 years after birth). The variance in maternal depressive symptoms explained by direct genetic effects ranged from 5% to 14%, whereas indirect genetic effects explained 0–14% of variance across time points. Heritable traits in family members contribute to maternal depressive symptoms through the environment at several time points after birth.
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Data availability
MoBa data can be accessed by application to the Regional Committee for Medical and Health 494 Research Ethics in Norway and MoBa (https://www.fhi.no/en/ch/studies/moba/for-forskere-artikler/research-and-data-access/). The consent given by the participants does not open for storage of data on an individual level in repositories or journals.
Code availability
The code used in this study is available upon request from the first author. Example code for fitting variance-component models structured according to relationship matrices with VCModels.jl is provided at: https://github.com/espenmei/VCModels.jl.
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Acknowledgements
The Research Council of Norway supported R.C., R.B.N., E.R., and T.A.M. (288083); H.A. (274611); A.H. (274611, 336085); L.D.B. (314843) and E.Y. 288083, 262177, 336078, and 331640). The South-Eastern Norway Regional Health Authority supported L.J.H. (2022083 and 2018058) and A.H. (2020022). L.D.B. has received internationalization support from UiO:Life Science. J.R.B. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (215917/Z/19/Z). The positions of T.A.M. and Y.I.A., were funded by a Wellcome Trust Senior Research Fellowship awarded to T.A.M. (220382/Z/20/Z). E.Y. is funded by the European Research Council under the Horizon 2020 (818425) and the Horizon Europa program (101045526). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.
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L.D.B., E.M.E. and E.Y. were responsible for the concept, design and analysis of data. L.D.B., E.M.E., Z.A., R.C., Y.I.A., J.R.B., H.A., L.J.H., T.A.M., A.H., R.B.N., E.R. and E.Y. contributed to the interpretation of the results. Drafting of the manuscript was done by L.D.B., while E.M.E., Z.A., R.C., Y.I.A., J.R.B., H.A., L.J.H., T.A.M., A.H., R.B.N., E.R. and E.Y. provided critical revision of the manuscript for important intellectual content.
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Bjørndal, L.D., Eilertsen, E.M., Ayorech, Z. et al. Disentangling direct and indirect genetic effects from partners and offspring on maternal depression using trio-GCTA. Nat. Mental Health 2, 417–425 (2024). https://doi.org/10.1038/s44220-024-00207-3
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DOI: https://doi.org/10.1038/s44220-024-00207-3
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