Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?

Eshim S Jami; Anke R Hammerschlag; Hannah M Sallis; Zhen Qiao; Ole A Andreassen; Per M Magnus; Pål R Njølstad; Alexandra Havdahl; Jean-Baptiste Pingault; David M Evans; Marcus R Munafò; Eivind Ystrom; Meike Bartels; Christel Middeldorp

doi:10.1038/s41398-023-02348-y

Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?

Eshim S Jami, Anke R Hammerschlag, Hannah M Sallis, Zhen Qiao, Ole A Andreassen, Per M Magnus, Pål R Njølstad, Alexandra Havdahl, Jean-Baptiste Pingault, David M Evans, Marcus R Munafò, Eivind Ystrom, Meike Bartels, Christel Middeldorp^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

1 Citation (Scopus)

Abstract

Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother-child pairs, and 6,222 father-child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes.

Original language	English
Article number	94
Journal	Translational Psychiatry
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41398-023-02348-y
Publication status	Published - 18 Mar 2023

Bibliographical note

Funding Information:
This work was supported by the European Union’s Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions—MSCA-ITN-2016—Innovative Training Networks (#721567; CAPICE project). 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. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. We also thank the NORMENT Centre for providing genotype data, funded by the Research Council of Norway (#223273), South East Norway Health Authority and KG Jebsen Stiftelsen. 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). This research is part of the HARVEST collaboration, supported by the Research Council of Norway (#229624). Data access and fees for this project are funded by the Research Council of Norway project #262177. ARH was supported by the Children’s Hospital Foundation and University of Queensland strategic funding. HMS and MRM are members of the MRC Integrative Epidemiology Unit at the University of Bristol. PRN is supported by the European Research Council (AdG SELECTionPREDISPOSED #293574), the Bergen Research Foundation (“Utilizing the Mother and Child Cohort and the Medical Birth Registry for Better Health”), Stiftelsen Kristian Gerhard Jebsen (Translational Medical Center), the University of Bergen, the Research Council of Norway (FRIPRO grant #240413), the Western Norway Regional Health Authority (Strategic Fund “Personalized Medicine for Children and Adults”), the Novo Nordisk Foundation (grant #54741), and the Norwegian Diabetes Association. AH was supported by the South-Eastern Norway Regional Health Authority (2018059) at Nic Waals Institute, Lovisenberg Diaconal Hospital. J-BP is supported by a European Research Council consolidator grant (grant number 863981 I-RISK). DME is supported by an NHMRC Senior Research Fellowship (GNT1137714). EY is supported by grants from the Research Council of Norway (262177 and 288083). MB is supported by a European Research Council consolidator grant (grant number 771067 WELL-BEING).

Funding Information:
This work was supported by the European Union’s Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions—MSCA-ITN-2016—Innovative Training Networks (#721567; CAPICE project). 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. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. We also thank the NORMENT Centre for providing genotype data, funded by the Research Council of Norway (#223273), South East Norway Health Authority and KG Jebsen Stiftelsen. 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). This research is part of the HARVEST collaboration, supported by the Research Council of Norway (#229624). Data access and fees for this project are funded by the Research Council of Norway project #262177. ARH was supported by the Children’s Hospital Foundation and University of Queensland strategic funding. HMS and MRM are members of the MRC Integrative Epidemiology Unit at the University of Bristol. PRN is supported by the European Research Council (AdG SELECTionPREDISPOSED #293574), the Bergen Research Foundation (“Utilizing the Mother and Child Cohort and the Medical Birth Registry for Better Health”), Stiftelsen Kristian Gerhard Jebsen (Translational Medical Center), the University of Bergen, the Research Council of Norway (FRIPRO grant #240413), the Western Norway Regional Health Authority (Strategic Fund “Personalized Medicine for Children and Adults”), the Novo Nordisk Foundation (grant #54741), and the Norwegian Diabetes Association. AH was supported by the South-Eastern Norway Regional Health Authority (2018059) at Nic Waals Institute, Lovisenberg Diaconal Hospital. J-BP is supported by a European Research Council consolidator grant (grant number 863981 I-RISK). DME is supported by an NHMRC Senior Research Fellowship (GNT1137714). EY is supported by grants from the Research Council of Norway (262177 and 288083). MB is supported by a European Research Council consolidator grant (grant number 771067 WELL-BEING).

Publisher Copyright:
© 2023, The Author(s).

Keywords

Female
Humans
Parents/psychology
Mothers/psychology
Attention Deficit Disorder with Hyperactivity/genetics
Genotype
Genetic Variation

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Jami, E. S., Hammerschlag, A. R., Sallis, H. M., Qiao, Z., Andreassen, O. A., Magnus, P. M., Njølstad, P. R., Havdahl, A., Pingault, J.-B., Evans, D. M., Munafò, M. R., Ystrom, E., Bartels, M., & Middeldorp, C. (2023). Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood? Translational Psychiatry, 13(1), Article 94. https://doi.org/10.1038/s41398-023-02348-y

@article{9ddf0091d1cc41d8830f87e3d2029a4e,

title = "Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?",

abstract = "Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother-child pairs, and 6,222 father-child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes.",

keywords = "Female, Humans, Parents/psychology, Mothers/psychology, Attention Deficit Disorder with Hyperactivity/genetics, Genotype, Genetic Variation",

author = "Jami, {Eshim S} and Hammerschlag, {Anke R} and Sallis, {Hannah M} and Zhen Qiao and Andreassen, {Ole A} and Magnus, {Per M} and Nj{\o}lstad, {P{\aa}l R} and Alexandra Havdahl and Jean-Baptiste Pingault and Evans, {David M} and Munaf{\`o}, {Marcus R} and Eivind Ystrom and Meike Bartels and Christel Middeldorp",

note = "Funding Information: This work was supported by the European Union{\textquoteright}s Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions—MSCA-ITN-2016—Innovative Training Networks (#721567; CAPICE project). 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. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. We also thank the NORMENT Centre for providing genotype data, funded by the Research Council of Norway (#223273), South East Norway Health Authority and KG Jebsen Stiftelsen. 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). This research is part of the HARVEST collaboration, supported by the Research Council of Norway (#229624). Data access and fees for this project are funded by the Research Council of Norway project #262177. ARH was supported by the Children{\textquoteright}s Hospital Foundation and University of Queensland strategic funding. HMS and MRM are members of the MRC Integrative Epidemiology Unit at the University of Bristol. PRN is supported by the European Research Council (AdG SELECTionPREDISPOSED #293574), the Bergen Research Foundation (“Utilizing the Mother and Child Cohort and the Medical Birth Registry for Better Health”), Stiftelsen Kristian Gerhard Jebsen (Translational Medical Center), the University of Bergen, the Research Council of Norway (FRIPRO grant #240413), the Western Norway Regional Health Authority (Strategic Fund “Personalized Medicine for Children and Adults”), the Novo Nordisk Foundation (grant #54741), and the Norwegian Diabetes Association. AH was supported by the South-Eastern Norway Regional Health Authority (2018059) at Nic Waals Institute, Lovisenberg Diaconal Hospital. J-BP is supported by a European Research Council consolidator grant (grant number 863981 I-RISK). DME is supported by an NHMRC Senior Research Fellowship (GNT1137714). EY is supported by grants from the Research Council of Norway (262177 and 288083). MB is supported by a European Research Council consolidator grant (grant number 771067 WELL-BEING). Funding Information: This work was supported by the European Union{\textquoteright}s Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions—MSCA-ITN-2016—Innovative Training Networks (#721567; CAPICE project). 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. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. We also thank the NORMENT Centre for providing genotype data, funded by the Research Council of Norway (#223273), South East Norway Health Authority and KG Jebsen Stiftelsen. 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). This research is part of the HARVEST collaboration, supported by the Research Council of Norway (#229624). Data access and fees for this project are funded by the Research Council of Norway project #262177. ARH was supported by the Children{\textquoteright}s Hospital Foundation and University of Queensland strategic funding. HMS and MRM are members of the MRC Integrative Epidemiology Unit at the University of Bristol. PRN is supported by the European Research Council (AdG SELECTionPREDISPOSED #293574), the Bergen Research Foundation (“Utilizing the Mother and Child Cohort and the Medical Birth Registry for Better Health”), Stiftelsen Kristian Gerhard Jebsen (Translational Medical Center), the University of Bergen, the Research Council of Norway (FRIPRO grant #240413), the Western Norway Regional Health Authority (Strategic Fund “Personalized Medicine for Children and Adults”), the Novo Nordisk Foundation (grant #54741), and the Norwegian Diabetes Association. AH was supported by the South-Eastern Norway Regional Health Authority (2018059) at Nic Waals Institute, Lovisenberg Diaconal Hospital. J-BP is supported by a European Research Council consolidator grant (grant number 863981 I-RISK). DME is supported by an NHMRC Senior Research Fellowship (GNT1137714). EY is supported by grants from the Research Council of Norway (262177 and 288083). MB is supported by a European Research Council consolidator grant (grant number 771067 WELL-BEING). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = mar,

day = "18",

doi = "10.1038/s41398-023-02348-y",

language = "English",

volume = "13",

journal = "Translational Psychiatry",

issn = "2158-3188",

publisher = "Springer Nature",