Do Polygenic Indices Capture “Direct” Effects on Child Externalizing Behavior Problems? Within-Family Analyses in Two Longitudinal Birth Cohorts

Abstract

Failures of self-control can manifest as externalizing behaviors (e.g., aggression, rule-breaking) that have far-reaching negative consequences. Researchers have long been interested in measuring children’s genetic risk for externalizing behaviors to inform efforts at early identification and intervention. Drawing on data from the Environmental Risk Longitudinal Twin Study (N = 862 twins) and the Millennium Cohort Study (N = 2,824 parent–child trios), two longitudinal cohorts from the United Kingdom, we leveraged molecular genetic data and within-family designs to test for genetic associations with externalizing behavior that are not affected by common sources of environmental influence. We found that a polygenic index (PGI) calculated from genetic variants discovered in previous studies of self-controlled behavior in adults captures direct genetic effects on externalizing problems in children and adolescents when evaluated with rigorous within-family designs (βs = 0.13–0.19 across development). The PGI for externalizing behavior can usefully augment psychological studies of the development of self-control.

Keywords

self-control externalizing polygenic index direct genetic effects development

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References

Achenbach

T. M.

(1997). Manual for the young adult self-report and young adult behavior checklist. University of Vermont.

Achenbach

T. M.

Edelbrock

(1991). Child behavior checklist. Burlington, 7, 371–392.

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.).

Barr

P. B.

Dick

D. M.

(2020). The genetics of externalizing problems. Current Topics in Behavioral Neurosciences, 47, 93–112. https://doi.org/10.1007/7854_2019_120

Beelmann

Arnold

L. S.

Hercher

(2022). Parent training programs for preventing and treating antisocial behavior in children and adolescents: A comprehensive meta-analysis of international studies. Aggression and Violent Behavior, 68, Article 101798. https://doi.org/10.1016/j.avb.2022.101798

Belsky

D. W.

Harden

K. P.

(2019). Phenotypic annotation: Using polygenic scores to translate discoveries from genome-wide association studies from the top down. Current Directions in Psychological Science, 28(1), 82–90.

Braga

Cunha

Maia

. (2018). The enduring effect of maltreatment on antisocial behavior: A meta-analysis of longitudinal studies. Aggression and Violent Behavior, 40, 91–100.

Bulmer

M. G.

(1980). The mathematical theory of quantitative genetics. Clarendon Press.

Burt

S. A.

(2009). Rethinking environmental contributions to child and adolescent psychopathology: A meta-analysis of shared environmental influences. Psychological Bulletin, 135(4), 608–637.

10.

Burt

S. A.

(2022). The genetic, environmental, and cultural forces influencing youth antisocial behavior are tightly intertwined. Annual Review of Clinical Psychology, 18, 155–178.

11.

Caspi

Taylor

Smart

Jackson

Tagami

Moffitt

T. E.

(2001). Can women provide reliable information about their children’s fathers? Cross-informant agreement about men’s lifetime antisocial behaviour. Journal of Child Psychology and Psychiatry and Allied Disciplines, 42(7), 915–920.

12.

Choi

S. W.

O’Reilly

P. F.

(2019). PRSice-2: Polygenic Risk Score software for biobank-scale data. Gigascience, 8(7), Article giz082. https://doi.org/10.1093/gigascience/giz082

13.

Connelly

Platt

(2014). Cohort profile: UK Millennium Cohort Study (MCS). International Journal of Epidemiology, 43(6), 1719–1725.

14.

Costa

P. T.

McCrae

R. R.

(1992). Normal personality assessment in clinical practice: The NEO Personality Inventory. Psychological Assessment, 4(1), 5–13.

15.

Demange

P. A.

Hottenga

J. J.

Abdellaoui

Eilertsen

E. M.

Malanchini

Domingue

B. W.

Armstrong-Carter

de Zeeuw

E. L.

Rimfeld

Boomsma

D. I.

van Bergen

Breen

Nivard

M. G.

Cheesman

(2022). Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores. Nature Communications, 13(1), Article 4801. https://doi.org/10.1038/s41467-022-32003-x

16.

Friedman

N. P.

Banich

M. T.

Keller

M. C.

(2021). Twin studies to GWAS: There and back again. Trends in Cognitive Sciences, 25(10), 855–869.

17.

Goodman

(1997). The Strengths and Difficulties Questionnaire: A research note. Journal of Child Psychology and Psychiatry, 38(5), 581–586. https://doi.org/10.1111/j.1469-7610.1997.tb01545.x

18.

Gottfredson

M. R.

Hirschi

(1990). A general theory of crime. Stanford University Press.

19.

Hannon

Knox

Sugden

Burrage

Wong

C. C. Y.

Belsky

D. W.

Corcoran

D. L.

Arseneault

Moffitt

T. E.

Caspi

Mill

(2018). Characterizing genetic and environmental influences on variable DNA methylation using monozygotic and dizygotic twins. PLOS Genetics, 14(8), Article e1007544. https://doi.org/10.1371/journal.pgen.1007544

20.

Hatoum

A. S.

Rhee

S. H.

Corley

R. P.

Hewitt

J. K.

Friedman

N. P.

(2018). Etiology of stability and growth of internalizing and externalizing behavior problems across childhood and adolescence. Behavior Genetics, 48(4), 298–314.

21.

Karlsson Linnér

Mallard

T. T.

Barr

P. B.

Sanchez-Roige

Madole

J. W.

Driver

M. N.

Poore

H. E.

de Vlaming

Grotzinger

A. D.

Tielbeek

J. J.

Johnson

E. C.

Liu

Rosenthal

S. B.

Ideker

Zhou

Kember

R. L.

Pasman

J. A.

Verweij

K. J. H.

Liu

D. J.

Dick

D. M

. (2021). Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction. Nature Neuroscience, 24(10), 1367–1376.

22.

Kaufman

J. S.

(2008). Commentary: Why are we biased against bias? International Journal of Epidemiology, 37(3), 624–626.

23.

Kendler

Gardner

Dick

(2011). Predicting alcohol consumption in adolescence from alcohol-specific and general externalizing genetic risk factors, key environmental exposures and their interaction. Psychological Medicine, 41(7), 1507–1516.

24.

Kong

Thorleifsson

Frigge

M. L.

Vilhjalmsson

B. J.

Young

A. I.

Thorgeirsson

T. E.

Benonisdottir

Oddsson

Halldorsson

B. V.

Masson

Gudbjartsson

D. F.

Helgason

Bjornsdottir

Thorsteinsdottir

Stefansson

(2018). The nature of nurture: Effects of parental genotypes. Science, 359(6374), 424–428.

25.

Kotov

Krueger

R. F.

Watson

Achenbach

T. M.

Althoff

R. R.

Bagby

R. M.

Brown

T. A.

Carpenter

W. T.

Caspi

Clark

L. A.

Eaton

N. R.

Forbes

M. K.

Forbush

K. T.

Goldberg

Hasin

Hyman

S. E.

Ivanova

M. Y.

Lynam

D. R.

Markon

. . . Zimmerman

(2017). The Hierarchical Taxonomy of Psychopathology (HiTOP): A dimensional alternative to traditional nosologies. Journal of Abnormal Psychology, 126(4), 454–477.

26.

Kretschmer

Vrijen

Nolte

I. M.

Wertz

Hartman

C. A.

(2022). Gene–environment interplay in externalizing behavior from childhood through adulthood. Journal of Child Psychology and Psychiatry, 63(10), 1206–1213.

27.

Kuo

S. I.

Poore

H. E.

Barr

P. B.

Chirico

I. S.

Aliev

Bucholz

K. K.

Chan

Kamarajan

Kramer

J. R.

McCutcheon

V. V.

Plawecki

M. H.

Dick

D. M.

(2022). The role of parental genotype in the intergenerational transmission of externalizing behavior: Evidence for genetic nurturance. Development and Psychopathology, 34(5), 1865–1875.

28.

Kuo

S. I.

Salvatore

J. E.

Barr

P. B.

Aliev

Anokhin

Bucholz

K. K.

Chan

Edenberg

H. J.

Hesselbrock

Kamarajan

Kramer

J. R.

Lai

Mallard

T. T.

Nurnberger

J. I.

Jr. Pandey

Plawecki

M. H.

Sanchez-Roige

Waldman

Palmer

A. A.

. . . Dick

D. M.

(2021). Mapping pathways by which genetic risk influences adolescent externalizing behavior: The interplay between externalizing polygenic risk scores, parental knowledge, and peer substance use. Behavior Genetics, 51(5), 543–558.

29.

Lynch

K. E.

(2017). Heritability and causal reasoning. Biology & Philosophy, 32(1), 25–49.

30.

Martin

A. R.

Kanai

Kamatani

Okada

Neale

B. M.

Daly

M. J.

(2019). Current clinical use of polygenic scores will risk exacerbating health disparities. Nature Genetics, 51(4), 584–591.

31.

Meyers

J. L.

Salvatore

J. E.

Vuoksimaa

Korhonen

Pulkkinen

Rose

R. J.

Kaprio

Dick

D. M.

(2014). Genetic influences on alcohol use behaviors have diverging developmental trajectories: A prospective study among male and female twins. Alcoholism: Clinical and Experimental Research, 38(11), 2869–2877.

32.

Moffitt

T. E.

Arseneault

Belsky

Dickson

Hancox

R. J.

Harrington

Houts

Poulton

Roberts

B. W.

Ross

Sears

M. R.

Thomson

W. M.

Caspi

(2011). A gradient of childhood self-control predicts health, wealth, and public safety. Proceedings of the National Academy of Sciences, USA, 108(7), 2693–2698.

33.

Moffitt

T. E.

Team

E. R. S.

(2002). Teen-aged mothers in contemporary Britain. Journal of Child Psychology and Psychiatry, 43(6), 727–742.

34.

Odgers

C. L.

Caspi

Russell

M. A.

Sampson

R. J.

Arseneault

Moffitt

T. E.

(2012). Supportive parenting mediates neighborhood socioeconomic disparities in children’s antisocial behavior from ages 5 to 12. Development and Psychopathology, 24(3), 705–721.

35.

Okbay

Wang

Jayashankar

Bennett

Nehzati

S. M.

Sidorenko

Kweon

Goldman

Gjorgjieva

Jiang

Hicks

Tian

Hinds

D. A.

Ahlskog

Magnusson

P. K. E.

Oskarsson

Hayward

Campbell

. . . Young

A. I.

(2022). Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals. Nature Genetics, 54(4), 437–449.

36.

Paradis

A. D.

Shenassa

E. D.

Papandonatos

G. D.

Rogers

M. L.

Buka

S. L.

(2017). Maternal smoking during pregnancy and offspring antisocial behaviour: Findings from a longitudinal investigation of discordant siblings. Journal of Epidemiology and Community Health, 71(9), 889–896.

37.

Pearson

A. L.

Shewark

E. A.

Burt

S. A.

(2022). Associations between neighborhood built, social, or toxicant conditions and child externalizing behaviors in the Detroit metro area: A cross-sectional study of the neighborhood ‘exposome.’ BMC Public Health, 22. Article 1064. https://doi.org/10.1186/s12889-022-13442-z

38.

Piccinelli

Tessari

Bortolomasi

Piasere

Semenzin

Garzotto

Tansella

(1997). Efficacy of the alcohol use disorders identification test as a screening tool for hazardous alcohol intake and related disorders in primary care: A validity study. British Medical Journal, 314(7078), Article 420. https://doi.org/10.1136%2Fbmj.314.7078.420

39.

Pingault

J. B.

Allegrini

A. G.

Odigie

Frach

Baldwin

J. R.

Rijsdijk

Dudbridge

(2022). Research review: How to interpret associations between polygenic scores, environmental risks, and phenotypes. Journal of Child Psychology and Psychiatry, 63(10), 1125–1139.

40.

Piotrowska

P. J.

Stride

C. B.

Croft

S. E.

Rowe

(2015). Socioeconomic status and antisocial behaviour among children and adolescents: A systematic review and meta-analysis. Clinical Psychology Review, 35, 47–55.

41.

Plomin

DeFries

J. C.

Loehlin

J. C.

(1977). Genotype-environment interaction and correlation in the analysis of human behavior. Psychological Bulletin, 84(2), 309–322.

42.

Pringsheim

Hirsch

Gardner

Gorman

D. A.

(2015). The pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder: A systematic review and meta-analysis. Part 1: Psychostimulants, alpha-2 agonists, and atomoxetine. The Canadian Journal of Psychiatry, 60(2), 42–51.

43.

Privé

Arbel

Vilhjálmsson

B. J.

(2020). LDpred2: Better, faster, stronger. Bioinformatics, 36(22–23), 5424–5431.

44.

Privé

Aschard

Carmi

Folkersen

Hoggart

O’Reilly

P. F.

Vilhjálmsson

B. J.

(2022). Portability of 245 polygenic scores when derived from the UK Biobank and applied to 9 ancestry groups from the same cohort. American Journal of Human Genetics, 109(1), 12–23.

45.

Raffington

Mallard

Harden

K. P.

(2020). Polygenic scores in developmental psychology: Invite genetics in, leave biodeterminism behind. Annual Review of Developmental Psychology, 2, 389–411.

46.

Reijntjes

Kamphuis

J. H.

Prinzie

Boelen

P. A.

Van der Schoot

Telch

M. J.

(2011). Prospective linkages between peer victimization and externalizing problems in children: A meta-analysis. Aggressive Behavior, 37(3), 215–222.

47.

Reuben

Schaefer

J. D.

Moffitt

T. E.

Broadbent

Harrington

Houts

R. M.

Ramrakha

Poulton

Caspi

(2019). Association of childhood lead exposure with adult personality traits and lifelong mental health. JAMA Psychiatry, 76(4), 418–425.

48.

Rivenbark

J. G.

Odgers

C. L.

Caspi

Harrington

Hogan

Houts

R. M.

Poulton

Moffitt

T. E.

(2018). The high societal costs of childhood conduct problems: Evidence from administrative records up to age 38 in a longitudinal birth cohort. Journal of Child Psychology and Psychiatry, 59(6), 703–710.

49.

Robins

L. N.

Cottler

Bucholz

Compton

North

C. S.

Rourke

K. M.

(1995). Diagnostic interview schedule for DSM-IV. Washington University Press.

50.

Sawyer

A. M.

Borduin

C. M.

Dopp

A. R.

(2015). Long-term effects of prevention and treatment on youth antisocial behavior: A meta-analysis. Clinical Psychology Review, 42, 130–144.

51.

Selzam

Ritchie

S. J.

Pingault

J.-B.

Reynolds

C. A.

O’Reilly

P. F.

Plomin

(2019). Comparing within-and between-family polygenic score prediction. American Journal of Human Genetics, 105(2), 351–363.

52.

Silventoinen

Jelenkovic

Sund

Latvala

Honda

Inui

Tomizawa

Watanabe

Sakai

Rebato

Busjahn

Tyler

Hopper

J. L.

Ordoñana

J. R.

Sánchez-Romera

J. F.

Colodro-Conde

Calais-Ferreira

Oliveira

V. C.

Ferreira

P. H.

. . . Kaprio

(2020). Genetic and environmental variation in educational attainment: An individual-based analysis of 28 twin cohorts. Scientific Reports, 10(1), Article 12681.

53.

Tanksley

P. T.

Barnes

J. C.

Boutwell

B. B.

Arseneault

Caspi

Danese

Fisher

H. L.

Moffitt

T. E.

(2020). Identifying psychological pathways to polyvictimization: Evidence from a longitudinal cohort study of twins from the UK. Journal of Experimental Criminology, 16, 431–461.

54.

Trejo

Domingue

B. W.

(2019). Genetic nature or genetic nurture? Quantifying bias in analyses using polygenic scores. bioRxiv. https://doi.org/10.1101/524850

55.

Westfall

Yarkoni

(2016). Statistically controlling for confounding constructs is harder than you think. PLOS ONE, 11(3), e0152719.

56.

Young

A. I.

Benonisdottir

Przeworski

Kong

(2019). Deconstructing the sources of genotype-phenotype associations in humans. Science, 365(6460), 1396–1400.

57.

Zhu

Ming

M. J.

Cole

J. M.

Kirkpatrick

Harpak

(2023). Amplification is the primary mode of gene-by-sex interaction in complex human traits. Cell Genomics, 3(5), Article 100297. https://doi.org/10.1016/j.xgen.2023.100297

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