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

doi:10.1007/s10519-020-10036-6

. 2021 Mar;51(2):154-161.

doi: 10.1007/s10519-020-10036-6. Epub 2021 Jan 2.

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

Espen Moen Eilertsen^{1

2

3}, Eshim Shahid Jami⁴, Tom A McAdams^{5

6}, Laurie J Hannigan⁷, Alexandra S Havdahl^{8

7

9

6}, Per Magnus¹⁰, David M Evans^{9

11}, Eivind Ystrom^{8

6

12}

Affiliations

¹ Department of Psychology, University of Oslo, Forskningsveien 3A, 0373, Oslo, Norway. e.m.eilertsen@psykologi.uio.no.
² Department of Psychology, PROMENTA Research Center, University of Oslo, Oslo, Norway. e.m.eilertsen@psykologi.uio.no.
³ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway. e.m.eilertsen@psykologi.uio.no.
⁴ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
⁵ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
⁶ Department of Psychology, PROMENTA Research Center, University of Oslo, Oslo, Norway.
⁷ Nic Waals Institute, Lovisenberg Diakonale Hospital, Oslo, Norway.
⁸ Department of Psychology, University of Oslo, Forskningsveien 3A, 0373, Oslo, Norway.
⁹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
¹⁰ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
¹¹ University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia.
¹² PharmacoEpidemiology and Drug Safety Research Group, School of Pharmacy, University of Oslo, Oslo, Norway.

PMID: 33387132
DOI: 10.1007/s10519-020-10036-6

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

Espen Moen Eilertsen et al. Behav Genet. 2021 Mar.

. 2021 Mar;51(2):154-161.

doi: 10.1007/s10519-020-10036-6. Epub 2021 Jan 2.

Authors

Espen Moen Eilertsen^{1

2

3}, Eshim Shahid Jami⁴, Tom A McAdams^{5

6}, Laurie J Hannigan⁷, Alexandra S Havdahl^{8

7

9

6}, Per Magnus¹⁰, David M Evans^{9

11}, Eivind Ystrom^{8

6

12}

Affiliations

¹ Department of Psychology, University of Oslo, Forskningsveien 3A, 0373, Oslo, Norway. e.m.eilertsen@psykologi.uio.no.
² Department of Psychology, PROMENTA Research Center, University of Oslo, Oslo, Norway. e.m.eilertsen@psykologi.uio.no.
³ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway. e.m.eilertsen@psykologi.uio.no.
⁴ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
⁵ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
⁶ Department of Psychology, PROMENTA Research Center, University of Oslo, Oslo, Norway.
⁷ Nic Waals Institute, Lovisenberg Diakonale Hospital, Oslo, Norway.
⁸ Department of Psychology, University of Oslo, Forskningsveien 3A, 0373, Oslo, Norway.
⁹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
¹⁰ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
¹¹ University of Queensland Diamantina Institute, University of Queensland, Brisbane, QLD, Australia.
¹² PharmacoEpidemiology and Drug Safety Research Group, School of Pharmacy, University of Oslo, Oslo, Norway.

PMID: 33387132
DOI: 10.1007/s10519-020-10036-6

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).

Keywords: Gene–environment correlation; Indirect genetic effects; MoBa; Trio-GCTA; Within-family.

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Examining intergenerational risk factors for conduct problems using polygenic scores in the Norwegian Mother, Father and Child Cohort Study.
Frach L, Barkhuizen W, Allegrini AG, Ask H, Hannigan LJ, Corfield EC, Andreassen OA, Dudbridge F, Ystrom E, Havdahl A, Pingault JB. Frach L, et al. Mol Psychiatry. 2024 Apr;29(4):951-961. doi: 10.1038/s41380-023-02383-7. Epub 2024 Jan 16. Mol Psychiatry. 2024. PMID: 38225381 Free PMC article.
The structure of psychiatric comorbidity without selection and assortative mating.
Ayorech Z, Torvik FA, Cheesman R, Eilertsen EM, Valstad M, Bjørndal LD, Røysamb E, Havdahl A, Ystrøm E. Ayorech Z, et al. Transl Psychiatry. 2024 Feb 26;14(1):121. doi: 10.1038/s41398-024-02768-4. Transl Psychiatry. 2024. PMID: 38409260 Free PMC article.
Estimating effects of parents' cognitive and non-cognitive skills on offspring education using polygenic scores.
Demange PA, Hottenga JJ, Abdellaoui A, Eilertsen EM, Malanchini M, Domingue BW, Armstrong-Carter E, de Zeeuw EL, Rimfeld K, Boomsma DI, van Bergen E, Breen G, Nivard MG, Cheesman R. Demange PA, et al. Nat Commun. 2022 Aug 23;13(1):4801. doi: 10.1038/s41467-022-32003-x. Nat Commun. 2022. PMID: 35999215 Free PMC article.
On the importance of parenting in externalizing disorders: an evaluation of indirect genetic effects in families.
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McAdams TA, Cheesman R, Ahmadzadeh YI. McAdams TA, et al. J Child Psychol Psychiatry. 2023 Apr;64(4):693-707. doi: 10.1111/jcpp.13720. Epub 2022 Nov 15. J Child Psychol Psychiatry. 2023. PMID: 36379220 Free PMC article. Review.

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References

1. Bates TC, Maher S, Medland SE, McAloney K, Wright MJ, Hansell NK, Kendler KS, Martin NG, Gillespie NA (2018) The nature of nurture: using a virtual-parent design to test parenting effects on children’s educational attainment in genotyped families. Twin Res Hum Genet 21(2):73–83 - DOI
1. Bijma P (2014) The quantitative genetics of indirect genetic effects: a selective review of modelling issues. Heredity 112(1):61–69 - DOI
1. Dyrdal GM, Røysamb E, Nes RB, Vittersø J (2011) Can a happy relationship predict a happy life? A populationbased study of maternal well-being during the life transition of pregnancy, infancy, and toddlerhood. J Happiness Stud 12(6):947–962 - DOI
1. Eaves LJ, Pourcain BS, Smith GD, York TP, Evans DM (2014) Resolving the effects of maternal and offspring genotype on dyadic outcomes in genome wide complex trait analysis (“M-GCTA”). Behav Genet 44(5):445–455 - DOI
1. Elks CE, Den Hoed M, Zhao JH, Sharp SJ, Wareham NJ, Loos RJF, Ong KK (2012) Variability in the heritability of body mass index: a systematic review and metaregression. Front Endocrinol 3:29 - DOI

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[1] Bates TC, Maher S, Medland SE, McAloney K, Wright MJ, Hansell NK, Kendler KS, Martin NG, Gillespie NA (2018) The nature of nurture: using a virtual-parent design to test parenting effects on children’s educational attainment in genotyped families. Twin Res Hum Genet 21(2):73–83 - DOI

[2] Bates TC, Maher S, Medland SE, McAloney K, Wright MJ, Hansell NK, Kendler KS, Martin NG, Gillespie NA (2018) The nature of nurture: using a virtual-parent design to test parenting effects on children’s educational attainment in genotyped families. Twin Res Hum Genet 21(2):73–83 - DOI

[3] Bijma P (2014) The quantitative genetics of indirect genetic effects: a selective review of modelling issues. Heredity 112(1):61–69 - DOI

[4] Bijma P (2014) The quantitative genetics of indirect genetic effects: a selective review of modelling issues. Heredity 112(1):61–69 - DOI

[5] Dyrdal GM, Røysamb E, Nes RB, Vittersø J (2011) Can a happy relationship predict a happy life? A populationbased study of maternal well-being during the life transition of pregnancy, infancy, and toddlerhood. J Happiness Stud 12(6):947–962 - DOI

[6] Dyrdal GM, Røysamb E, Nes RB, Vittersø J (2011) Can a happy relationship predict a happy life? A populationbased study of maternal well-being during the life transition of pregnancy, infancy, and toddlerhood. J Happiness Stud 12(6):947–962 - DOI

[7] Eaves LJ, Pourcain BS, Smith GD, York TP, Evans DM (2014) Resolving the effects of maternal and offspring genotype on dyadic outcomes in genome wide complex trait analysis (“M-GCTA”). Behav Genet 44(5):445–455 - DOI

[8] Eaves LJ, Pourcain BS, Smith GD, York TP, Evans DM (2014) Resolving the effects of maternal and offspring genotype on dyadic outcomes in genome wide complex trait analysis (“M-GCTA”). Behav Genet 44(5):445–455 - DOI

[9] Elks CE, Den Hoed M, Zhao JH, Sharp SJ, Wareham NJ, Loos RJF, Ong KK (2012) Variability in the heritability of body mass index: a systematic review and metaregression. Front Endocrinol 3:29 - DOI

[10] Elks CE, Den Hoed M, Zhao JH, Sharp SJ, Wareham NJ, Loos RJF, Ong KK (2012) Variability in the heritability of body mass index: a systematic review and metaregression. Front Endocrinol 3:29 - DOI

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

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

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