Direct and Indirect Genetic Effects on Aggression

Camiel M. van der Laan; Steve G.A. van de Weijer; René Pool; Jouke Jan Hottenga; Toos C.E.M. van Beijsterveldt; Gonneke Willemsen; Meike Bartels; Michel G. Nivard; Dorret I. Boomsma

doi:10.1016/j.bpsgos.2023.04.006

Direct and Indirect Genetic Effects on Aggression

Camiel M. van der Laan^*, Steve G.A. van de Weijer, René Pool, Jouke Jan Hottenga, Toos C.E.M. van Beijsterveldt, Gonneke Willemsen, Meike Bartels, Michel G. Nivard, Dorret I. Boomsma

^*Corresponding author for this work

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

Abstract

Background: Family members resemble each other in their propensity for aggression. In twin studies, approximately 50% of the variance in aggression can be explained by genetic influences. However, if there are genotype-environment correlation mechanisms, such as environmental manifestations of parental and sibling genotypes, genetic influences may partly reflect environmental influences. In this study, we investigated the importance of indirect polygenic score (PGS) effects on aggression. Methods: We modeled the effect of PGSs based on 3 genome-wide association studies: early-life aggression, educational attainment, and attention-deficit/hyperactivity disorder (ADHD). The associations with aggression were tested in a within- and between-family design (37,796 measures from 7740 individuals, ages 3–86 years [mean = 14.20 years, SE = 12.03], from 3107 families, 55% female) and in a transmitted/nontransmitted PGS design (42,649 measures from 6653 individuals, ages 3–61 years [mean = 11.81 years, SE = 8.68], from 3024 families, 55% female). All participants are enrolled in the Netherlands Twin Register. Results: We found no evidence for contributions of indirect PGS effects on aggression in either a within- and between-family design or a transmitted/nontransmitted PGS design. Results indicate significant direct effects on aggression for the PGSs based on early-life aggression, educational attainment, and ADHD, although explained variance was low (within- and between-family: early-life aggression R² = 0.3%, early-life ADHD R² = 0.6%, educational attainment R² = 0.7%; transmitted/nontransmitted PGSs: early-life aggression R² = 0.2%, early-life ADHD R² = 0.9%, educational attainment R² = 0.5%). Conclusions: PGSs included in the current study had a direct (but no indirect) effect on aggression, consistent with results of previous twin and family studies. Further research involving other PGSs for aggression and related phenotypes is needed to determine whether this conclusion generalizes to overall genetic influences on aggression.

Original language	English
Pages (from-to)	958-968
Number of pages	11
Journal	Biological psychiatry global open science
Volume	3
Issue number	4
Early online date	29 Apr 2023
DOIs	https://doi.org/10.1016/j.bpsgos.2023.04.006
Publication status	Published - Oct 2023

Bibliographical note

Funding Information:
This work was supported by multiple grants from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW): Genetic influences on stability and change in psychopathology from childhood to young adulthood (Grant No. ZonMw 912-10-020); Twin family database for behavior genomics studies (Grant No. NWO 480-04-004); Genetic and Family Influences on Adolescent. Psychopathology and Wellness (Grant No. NWO 463-06-001); A Twin–Sibling Study of Adolescent Wellness (Grant No. 451-04-034); Twin research focusing on behavior (Grant No. NWO 400-05-717); Longitudinal data collection from teachers of Dutch twins and their siblings (Grant No. 481-08-011); Twin-family study of individual differences in school achievement (Grant No. NWO-FES, 056-32-010); Genotype/phenotype database for behavior genetic and genetic epidemiological studies (Grant No. ZonMw Middelgroot 911-09-032); “Why some children thrive” (Grant No. OCW_Gravity program –NWO-024.001.003), Netherlands Twin Registry Repository: researching the interplay between genome and environment (Grant No. NWO-Groot 480-15-001/674); BBMRI –NL (Grant Nos. 184.021.007 and 184.033.111): Biobanking and Biomolecular Resources Research Infrastructure; Spinozapremie (Grant No. NWO- 6-464-14192 [to DIB]) and KNAW Academy Professor Award (Grant No. PAH/6635 [to DIB]); the Neuroscience Campus Amsterdam and Amsterdam Public Health; the European Research Council Genetics of Mental Illness ( European Research Council Advanced, 230374 ); National Institutes of Health: Rutgers University Cell and DNA Repository cooperative agreement ( National Institute of Mental Health Grant No. U24 MH068457-06 ); Developmental Study of Attention Problems in Young Twins ( National Institute of Mental Health , Grant No. RO1 MH58799-03 ); Grand Opportunity grant Developmental trajectories of psychopathology ( National Institute of Mental Health Grant No. 1RC2 MH089995 ); Grant No. RO1DK092127 from the National Institute of Diabetes and Digestive and Kidney Diseases and the Avera Institute for Human Genetics. CMvdL was supported by the Amsterdam Law and Behavior Institute (Vrije Universtiteit, Amsterdam). SGAvdW was supported by NWO Grant No. 451-16-014. MGN is supported by ZonMW Grants No. 849200011 and No. 531003014 from the Netherlands Organization for Health Research and Development, a VENI grant awarded by NWO (VI.Veni.191G.030), and National Institutes of Health (Grant No. R01MH120219) . MB is supported by a European Research Council Consolidator grant (WELL-BEING 771057).

Publisher Copyright:
© 2023 The Authors

Funding

This work was supported by multiple grants from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW): Genetic influences on stability and change in psychopathology from childhood to young adulthood (Grant No. ZonMw 912-10-020); Twin family database for behavior genomics studies (Grant No. NWO 480-04-004); Genetic and Family Influences on Adolescent. Psychopathology and Wellness (Grant No. NWO 463-06-001); A Twin–Sibling Study of Adolescent Wellness (Grant No. 451-04-034); Twin research focusing on behavior (Grant No. NWO 400-05-717); Longitudinal data collection from teachers of Dutch twins and their siblings (Grant No. 481-08-011); Twin-family study of individual differences in school achievement (Grant No. NWO-FES, 056-32-010); Genotype/phenotype database for behavior genetic and genetic epidemiological studies (Grant No. ZonMw Middelgroot 911-09-032); “Why some children thrive” (Grant No. OCW_Gravity program –NWO-024.001.003), Netherlands Twin Registry Repository: researching the interplay between genome and environment (Grant No. NWO-Groot 480-15-001/674); BBMRI –NL (Grant Nos. 184.021.007 and 184.033.111): Biobanking and Biomolecular Resources Research Infrastructure; Spinozapremie (Grant No. NWO- 6-464-14192 [to DIB]) and KNAW Academy Professor Award (Grant No. PAH/6635 [to DIB]); the Neuroscience Campus Amsterdam and Amsterdam Public Health; the European Research Council Genetics of Mental Illness ( European Research Council Advanced, 230374 ); National Institutes of Health: Rutgers University Cell and DNA Repository cooperative agreement ( National Institute of Mental Health Grant No. U24 MH068457-06 ); Developmental Study of Attention Problems in Young Twins ( National Institute of Mental Health , Grant No. RO1 MH58799-03 ); Grand Opportunity grant Developmental trajectories of psychopathology ( National Institute of Mental Health Grant No. 1RC2 MH089995 ); Grant No. RO1DK092127 from the National Institute of Diabetes and Digestive and Kidney Diseases and the Avera Institute for Human Genetics. CMvdL was supported by the Amsterdam Law and Behavior Institute (Vrije Universtiteit, Amsterdam). SGAvdW was supported by NWO Grant No. 451-16-014. MGN is supported by ZonMW Grants No. 849200011 and No. 531003014 from the Netherlands Organization for Health Research and Development, a VENI grant awarded by NWO (VI.Veni.191G.030), and National Institutes of Health (Grant No. R01MH120219) . MB is supported by a European Research Council Consolidator grant (WELL-BEING 771057).

Funders	Funder number
National Institute of Diabetes and Digestive and Kidney Diseases
European Research Council Genetics of Mental Illness
National Institutes of Health
European Commission
Avera Institute for Human Genetics	IRB00002991, 03-180, R01MH120219, FWA00017598, VI.Veni.191G.030, 451-16-014, 849200011, 531003014, WELL-BEING 771057
Horizon 2020 Framework Programme	771057
Koninklijke Nederlandse Akademie van Wetenschappen	PAH/6635
National Institute of Mental Health	1RC2 MH089995, RO1DK092127, RO1 MH58799-03, U24 MH068457-06
European Research Council	230374
BBMRI	184.033.111, NWO- 6-464-14192, 184.021.007
ZonMw	NWO 400-05-717, Middelgroot 911-09-032, NWO-024.001.003, NWO 480-04-004, 451-04-034, 056-32-010, NWO 463-06-001, ZonMw 912-10-020, NWO-Groot 480-15-001/674
Not added	481-08-011

Keywords

Aggression
Genetic nurture
Indirect genetic effects
Polygenic score
Transmitted/nontransmitted alleles
Within-family

Cohort Studies

Netherlands Twin Register (NTR)

Access to Document

10.1016/j.bpsgos.2023.04.006

Persistent URL (handle)

Persistent link

Cite this

@article{a2f48b57d0e14cc4ba93d147ddb17cc8,

title = "Direct and Indirect Genetic Effects on Aggression",

abstract = "Background: Family members resemble each other in their propensity for aggression. In twin studies, approximately 50\% of the variance in aggression can be explained by genetic influences. However, if there are genotype-environment correlation mechanisms, such as environmental manifestations of parental and sibling genotypes, genetic influences may partly reflect environmental influences. In this study, we investigated the importance of indirect polygenic score (PGS) effects on aggression. Methods: We modeled the effect of PGSs based on 3 genome-wide association studies: early-life aggression, educational attainment, and attention-deficit/hyperactivity disorder (ADHD). The associations with aggression were tested in a within- and between-family design (37,796 measures from 7740 individuals, ages 3–86 years [mean = 14.20 years, SE = 12.03], from 3107 families, 55\% female) and in a transmitted/nontransmitted PGS design (42,649 measures from 6653 individuals, ages 3–61 years [mean = 11.81 years, SE = 8.68], from 3024 families, 55\% female). All participants are enrolled in the Netherlands Twin Register. Results: We found no evidence for contributions of indirect PGS effects on aggression in either a within- and between-family design or a transmitted/nontransmitted PGS design. Results indicate significant direct effects on aggression for the PGSs based on early-life aggression, educational attainment, and ADHD, although explained variance was low (within- and between-family: early-life aggression R2 = 0.3\%, early-life ADHD R2 = 0.6\%, educational attainment R2 = 0.7\%; transmitted/nontransmitted PGSs: early-life aggression R2 = 0.2\%, early-life ADHD R2 = 0.9\%, educational attainment R2 = 0.5\%). Conclusions: PGSs included in the current study had a direct (but no indirect) effect on aggression, consistent with results of previous twin and family studies. Further research involving other PGSs for aggression and related phenotypes is needed to determine whether this conclusion generalizes to overall genetic influences on aggression.",

keywords = "Aggression, Genetic nurture, Indirect genetic effects, Polygenic score, Transmitted/nontransmitted alleles, Within-family",

author = "\{van der Laan\}, \{Camiel M.\} and \{van de Weijer\}, \{Steve G.A.\} and Ren{\'e} Pool and Hottenga, \{Jouke Jan\} and \{van Beijsterveldt\}, \{Toos C.E.M.\} and Gonneke Willemsen and Meike Bartels and Nivard, \{Michel G.\} and Boomsma, \{Dorret I.\}",

note = "Funding Information: This work was supported by multiple grants from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW): Genetic influences on stability and change in psychopathology from childhood to young adulthood (Grant No. ZonMw 912-10-020); Twin family database for behavior genomics studies (Grant No. NWO 480-04-004); Genetic and Family Influences on Adolescent. Psychopathology and Wellness (Grant No. NWO 463-06-001); A Twin–Sibling Study of Adolescent Wellness (Grant No. 451-04-034); Twin research focusing on behavior (Grant No. NWO 400-05-717); Longitudinal data collection from teachers of Dutch twins and their siblings (Grant No. 481-08-011); Twin-family study of individual differences in school achievement (Grant No. NWO-FES, 056-32-010); Genotype/phenotype database for behavior genetic and genetic epidemiological studies (Grant No. ZonMw Middelgroot 911-09-032); “Why some children thrive” (Grant No. OCW\_Gravity program –NWO-024.001.003), Netherlands Twin Registry Repository: researching the interplay between genome and environment (Grant No. NWO-Groot 480-15-001/674); BBMRI –NL (Grant Nos. 184.021.007 and 184.033.111): Biobanking and Biomolecular Resources Research Infrastructure; Spinozapremie (Grant No. NWO- 6-464-14192 [to DIB]) and KNAW Academy Professor Award (Grant No. PAH/6635 [to DIB]); the Neuroscience Campus Amsterdam and Amsterdam Public Health; the European Research Council Genetics of Mental Illness ( European Research Council Advanced, 230374 ); National Institutes of Health: Rutgers University Cell and DNA Repository cooperative agreement ( National Institute of Mental Health Grant No. U24 MH068457-06 ); Developmental Study of Attention Problems in Young Twins ( National Institute of Mental Health , Grant No. RO1 MH58799-03 ); Grand Opportunity grant Developmental trajectories of psychopathology ( National Institute of Mental Health Grant No. 1RC2 MH089995 ); Grant No. RO1DK092127 from the National Institute of Diabetes and Digestive and Kidney Diseases and the Avera Institute for Human Genetics. CMvdL was supported by the Amsterdam Law and Behavior Institute (Vrije Universtiteit, Amsterdam). SGAvdW was supported by NWO Grant No. 451-16-014. MGN is supported by ZonMW Grants No. 849200011 and No. 531003014 from the Netherlands Organization for Health Research and Development, a VENI grant awarded by NWO (VI.Veni.191G.030), and National Institutes of Health (Grant No. R01MH120219) . MB is supported by a European Research Council Consolidator grant (WELL-BEING 771057). Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = oct,

doi = "10.1016/j.bpsgos.2023.04.006",

language = "English",

volume = "3",

pages = "958--968",

journal = "Biological psychiatry global open science",

issn = "2667-1743",

publisher = "Elsevier Inc.",

number = "4",

}

TY - JOUR

T1 - Direct and Indirect Genetic Effects on Aggression

AU - van der Laan, Camiel M.

AU - van de Weijer, Steve G.A.

AU - Pool, René

AU - Hottenga, Jouke Jan

AU - van Beijsterveldt, Toos C.E.M.

AU - Willemsen, Gonneke

AU - Bartels, Meike

AU - Nivard, Michel G.

AU - Boomsma, Dorret I.

N1 - Funding Information: This work was supported by multiple grants from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW): Genetic influences on stability and change in psychopathology from childhood to young adulthood (Grant No. ZonMw 912-10-020); Twin family database for behavior genomics studies (Grant No. NWO 480-04-004); Genetic and Family Influences on Adolescent. Psychopathology and Wellness (Grant No. NWO 463-06-001); A Twin–Sibling Study of Adolescent Wellness (Grant No. 451-04-034); Twin research focusing on behavior (Grant No. NWO 400-05-717); Longitudinal data collection from teachers of Dutch twins and their siblings (Grant No. 481-08-011); Twin-family study of individual differences in school achievement (Grant No. NWO-FES, 056-32-010); Genotype/phenotype database for behavior genetic and genetic epidemiological studies (Grant No. ZonMw Middelgroot 911-09-032); “Why some children thrive” (Grant No. OCW_Gravity program –NWO-024.001.003), Netherlands Twin Registry Repository: researching the interplay between genome and environment (Grant No. NWO-Groot 480-15-001/674); BBMRI –NL (Grant Nos. 184.021.007 and 184.033.111): Biobanking and Biomolecular Resources Research Infrastructure; Spinozapremie (Grant No. NWO- 6-464-14192 [to DIB]) and KNAW Academy Professor Award (Grant No. PAH/6635 [to DIB]); the Neuroscience Campus Amsterdam and Amsterdam Public Health; the European Research Council Genetics of Mental Illness ( European Research Council Advanced, 230374 ); National Institutes of Health: Rutgers University Cell and DNA Repository cooperative agreement ( National Institute of Mental Health Grant No. U24 MH068457-06 ); Developmental Study of Attention Problems in Young Twins ( National Institute of Mental Health , Grant No. RO1 MH58799-03 ); Grand Opportunity grant Developmental trajectories of psychopathology ( National Institute of Mental Health Grant No. 1RC2 MH089995 ); Grant No. RO1DK092127 from the National Institute of Diabetes and Digestive and Kidney Diseases and the Avera Institute for Human Genetics. CMvdL was supported by the Amsterdam Law and Behavior Institute (Vrije Universtiteit, Amsterdam). SGAvdW was supported by NWO Grant No. 451-16-014. MGN is supported by ZonMW Grants No. 849200011 and No. 531003014 from the Netherlands Organization for Health Research and Development, a VENI grant awarded by NWO (VI.Veni.191G.030), and National Institutes of Health (Grant No. R01MH120219) . MB is supported by a European Research Council Consolidator grant (WELL-BEING 771057). Publisher Copyright: © 2023 The Authors

PY - 2023/10

Y1 - 2023/10

N2 - Background: Family members resemble each other in their propensity for aggression. In twin studies, approximately 50% of the variance in aggression can be explained by genetic influences. However, if there are genotype-environment correlation mechanisms, such as environmental manifestations of parental and sibling genotypes, genetic influences may partly reflect environmental influences. In this study, we investigated the importance of indirect polygenic score (PGS) effects on aggression. Methods: We modeled the effect of PGSs based on 3 genome-wide association studies: early-life aggression, educational attainment, and attention-deficit/hyperactivity disorder (ADHD). The associations with aggression were tested in a within- and between-family design (37,796 measures from 7740 individuals, ages 3–86 years [mean = 14.20 years, SE = 12.03], from 3107 families, 55% female) and in a transmitted/nontransmitted PGS design (42,649 measures from 6653 individuals, ages 3–61 years [mean = 11.81 years, SE = 8.68], from 3024 families, 55% female). All participants are enrolled in the Netherlands Twin Register. Results: We found no evidence for contributions of indirect PGS effects on aggression in either a within- and between-family design or a transmitted/nontransmitted PGS design. Results indicate significant direct effects on aggression for the PGSs based on early-life aggression, educational attainment, and ADHD, although explained variance was low (within- and between-family: early-life aggression R2 = 0.3%, early-life ADHD R2 = 0.6%, educational attainment R2 = 0.7%; transmitted/nontransmitted PGSs: early-life aggression R2 = 0.2%, early-life ADHD R2 = 0.9%, educational attainment R2 = 0.5%). Conclusions: PGSs included in the current study had a direct (but no indirect) effect on aggression, consistent with results of previous twin and family studies. Further research involving other PGSs for aggression and related phenotypes is needed to determine whether this conclusion generalizes to overall genetic influences on aggression.

AB - Background: Family members resemble each other in their propensity for aggression. In twin studies, approximately 50% of the variance in aggression can be explained by genetic influences. However, if there are genotype-environment correlation mechanisms, such as environmental manifestations of parental and sibling genotypes, genetic influences may partly reflect environmental influences. In this study, we investigated the importance of indirect polygenic score (PGS) effects on aggression. Methods: We modeled the effect of PGSs based on 3 genome-wide association studies: early-life aggression, educational attainment, and attention-deficit/hyperactivity disorder (ADHD). The associations with aggression were tested in a within- and between-family design (37,796 measures from 7740 individuals, ages 3–86 years [mean = 14.20 years, SE = 12.03], from 3107 families, 55% female) and in a transmitted/nontransmitted PGS design (42,649 measures from 6653 individuals, ages 3–61 years [mean = 11.81 years, SE = 8.68], from 3024 families, 55% female). All participants are enrolled in the Netherlands Twin Register. Results: We found no evidence for contributions of indirect PGS effects on aggression in either a within- and between-family design or a transmitted/nontransmitted PGS design. Results indicate significant direct effects on aggression for the PGSs based on early-life aggression, educational attainment, and ADHD, although explained variance was low (within- and between-family: early-life aggression R2 = 0.3%, early-life ADHD R2 = 0.6%, educational attainment R2 = 0.7%; transmitted/nontransmitted PGSs: early-life aggression R2 = 0.2%, early-life ADHD R2 = 0.9%, educational attainment R2 = 0.5%). Conclusions: PGSs included in the current study had a direct (but no indirect) effect on aggression, consistent with results of previous twin and family studies. Further research involving other PGSs for aggression and related phenotypes is needed to determine whether this conclusion generalizes to overall genetic influences on aggression.

KW - Aggression

KW - Genetic nurture

KW - Indirect genetic effects

KW - Polygenic score

KW - Transmitted/nontransmitted alleles

KW - Within-family

UR - https://www.scopus.com/pages/publications/85166950044

UR - https://www.scopus.com/inward/citedby.url?scp=85166950044&partnerID=8YFLogxK

U2 - 10.1016/j.bpsgos.2023.04.006

DO - 10.1016/j.bpsgos.2023.04.006

M3 - Article

AN - SCOPUS:85166950044

SN - 2667-1743

VL - 3

SP - 958

EP - 968

JO - Biological psychiatry global open science

JF - Biological psychiatry global open science

IS - 4

ER -

Direct and Indirect Genetic Effects on Aggression

Abstract

Bibliographical note

Funding

Keywords

Cohort Studies

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