Intergenerational continuity in parents' and adolescents' externalizing problems: The role of life events and their interaction with GABRA2.

paper Primary Public

Authors: Salvatore, Jessica E; Meyers, Jacquelyn L; Yan, Jia; Aliev, Fazil; Lansford, Jennifer E; Pettit, Gregory S; Bates, John E; Dodge, Kenneth A; Rose, Richard J; Pulkkinen, Lea; Kaprio, Jaakko; Dick, Danielle M
Year: 2015
Journal: Journal of abnormal psychology
PMID: 26075969
DOI: 10.1037/abn0000066
PMCID: PMC4573794

Figure 1

Panel A plots Child Behavior Checklist (CBCL) adolescent externalizing as a function of life events (high = +1 SD above the mean, low = −1 SD below the mean) and the number of copies of the minor allele for GABRA2 SNP rs279871 for the model including parental antisocial behavior in the Child Development Project sample. Panel B further delineates the shape of the interaction for the model including parental antisocial behavior as a function of GABRA2 SNP rs279871 and high and low life events for an illustrative time point (age 12). Bars represent the standard errors of the estimates.

Figure 2

Strength of the association (depicted as standardized betas) between life events, Child Behavior Checklist (CBCL) externalizing (left), and Teacher Report Form (TRF) externalizing (right) as a function of the number of copies of the minor allele for GABRA2 SNP rs279871 for the models including parental antisocial behavior (panel A) and parental alcohol problems (panel B) in the Child Development Project sample. Bars represent the 95% confidence intervals for the estimates.

Figure 3

Teacher Report Form (TRF) externalizing as a function of life events (high = +1 SD above the mean, low = −1 SD below the mean) and the number of copies of the minor allele for GABRA2 SNP rs279871 for the model including parental antisocial behavior (panel A) in the Child Development Project sample. Panel B further delineates the shape of the interaction for the model including parental antisocial behavior as a function of GABRA2 SNP rs279871 and high and low life events for an illustrative time point (age 12). Bars represent the standard errors of the estimates.

Figure 4

Teacher-reported adolescent externalizing as a function of life events (high = +1 SD above the mean, low = −1 SD below the mean) and the number of copies of the minor allele for GABRA2 SNP rs279871 for the model including parental antisocial behavior in the FinnTwin12 sample. Bars represent the standard errors of the estimates.

Figure 5

Strength of the association (depicted as standardized betas) between life events and teacher-reported adolescent externalizing as a function of the number of copies of the minor allele for GABRA2 SNP rs279871 for the models including parental antisocial behavior (panel A) and parental alcohol dependence symptoms (panel B) in the FinnTwin12 sample. Bars represent the 95% confidence intervals for the estimates.

#	Section	Preview
0	Method — Discovery Sample: Child Development Project	Participants in the present study are the European-American subsample (n = 324) of the Child…
1	Method — Discovery Sample: Child Development Project — Parental Antisocial Behavior and Alcohol Problems	Mothers and fathers (if available) reported on their own lifetime antisocial behavior and alcohol…
2	Method — Discovery Sample: Child Development Project — Parental Antisocial Behavior and Alcohol Problems	The antisocial behavior scale was adapted from Frick and Hare (2001), and each parent reported how…
3	Method — Discovery Sample: Child Development Project — Parental Antisocial Behavior and Alcohol Problems	Alcohol problems were assessed using twelve items from the Short Michigan Alcohol Screening Test…
4	Method — Discovery Sample: Child Development Project — Life events	At each annual assessment between ages 11–16, life events experienced by the child and his/her…
5	Method — Discovery Sample: Child Development Project — Externalizing behavior [mother (CBCL) and teacher (TRF) reports]	At each annual assessment at ages 12–17 mother-reported externalizing behavior was assessed using…
6	Method — Discovery Sample: Child Development Project — Externalizing behavior [mother (CBCL) and teacher (TRF) reports]	and divergent validity (Achenbach, 1991a, 1991c). Separate mother and teacher externalizing symptom…
7	Method — Discovery Sample: Child Development Project — Genotyping	We genotyped 10 single nucleotide polymorphisms (SNPs) in GABRA2, which were selected based on…
8	Method — Discovery Sample: Child Development Project — Covariates	Sex was entered as a covariate in view of previous sex differences for this outcome (Newman et al.,…
9	Method — Replication Sample: FinnTwin12	FinnTwin12 is a population-based Finnish twin sample of approximately 2,700 twin pairs; of these…
10	Method — Replication Sample: FinnTwin12 — Parental Antisocial Behavior and Alcohol Dependence Symptoms	Maternal and paternal antisocial behavior was indexed using symptom counts for DSM-3-R (American…
11	Method — Replication Sample: FinnTwin12 — Parental Antisocial Behavior and Alcohol Dependence Symptoms	Maternal and paternal alcohol dependence symptoms were indexed using lifetime symptom counts for…
12	Method — Replication Sample: FinnTwin12 — Life Events	At age 14, twins reported on their life events using a checklist that asked whether a series of 15…
13	Method — Replication Sample: FinnTwin12 — Externalizing Behavior	At age 14, externalizing behavior was measured using the Behavioral Problems scale from the Teacher…
14	Method — Replication Sample: FinnTwin12 — Covariates	As with CDP, we statistically controlled for sex and for the number of parental reports for…
15	Method — Replication Sample: FinnTwin12 — Genotyping	Genome-wide data were collected using blood samples obtained at the age 22 assessment. Genotyping…
16	Method — Replication Sample: FinnTwin12 — Genotyping	using ShapeIT (Delaneau, Marchini, & Zagury, 2012) in pre-phasing and IMPUTE2 (Howie, Donnelly, &…
17	Method — Analytic Plan — CDP	Six time points of repeated-measures data were available for both life events and CBCL…
18	Method — Analytic Plan — CDP	Per the recommendations of MacKinnon et al. (2002), we tested for the indirect effect of parental…
19	Method — Analytic Plan — CDP	Parental Externalizing Predicting Life Events

Citation	PMID	DOI	Status
Achenbach, TM, Manual for Teacher’s Report Form and 1991 profile	—	—	—
Achenbach, TM, Manual for the Child Behavior Checklist and 1991 profile	—	—	—
Agrawal, A et al., Behavior Genetics, 2006, Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample	16622805	10.1007/s10519-006-9069-4	Primary
Bennett, ME et al., Journal of Studies on Alcohol, 1999, Problem drinking from young adulthood to adulthood: Patterns, predictors, and outcomes	10487729	10.15288/jsa.1999.60.605	Cited
Beuten, J et al., American Journal of Human Genetics, 2005, Single- and multilocus allelic variants within the GABA(B) receptor subunit 2 (GABAB2) gene are significantly associated with nicotine dependence	15759211	10.1086/429839	Cited
Blomeyer, D et al., Biological Psychiatry, 2008, Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use	17597588	10.1016/j.biopsych.2007.04.026	Cited
Broms, U et al., Nicotine & Tobacco Research, 2012, Analysis of detailed phenotype profiles reveals CHRNA5-CHRNA3-CHRNB4 gene cluster association with several nicotine dependence traits	22241830	10.1093/ntr/ntr283	Cited
Bucholz, KK et al., Journal of Studies on Alcohol, 1994, A new, semi-structured psychiatric interview for use in genetic linkage studies: A report on the reliability of the SSAGA	8189735	10.15288/jsa.1994.55.149	Primary
Chassin, L et al., Journal of Abnormal Psychology, 1993, Relation of parental alcoholism to early adolescent substance use: A test of 3 mediating mechanisms	8436697	10.1037//0021-843x.102.1.3	Cited
Chassin, L et al., Journal of Abnormal Psychology, 1996, The relation of parent alcoholism to adolescent substance use: A longitudinal follow-up study	8666713	10.1037/0021-843X.105.1.70	Cited
Conger, RD et al., Child Development, 1995, It takes 2 to replicate: A mediational model for the impact of parents’ stress on adolescent adjustment	7497831	10.1111/j.1467-8624.1995.tb00857.x	Cited
Covault, J et al., American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 2004, Allelic and haplotypic association of GABRA2 with alcohol dependence	15274050	10.1002/ajmg.b.30091	Cited
Covault, J et al., Biological Psychiatry, 2007, Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug use	16920076	10.1016/j.biopsych.2006.05.018	Cited
Dai, J et al., Stress and Health, 2009, Expression quantitative trait loci and genetic regulatory network analysis reveals that Gabra2 is involved in stress responses in the mouse	19212922	10.3109/10253890802666112	Cited
Delaneau, O et al., Nature Methods, 2012, A linear complexity phasing method for thousands of genomes	22138821	10.1038/nmeth.1785	Cited
Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, 1987	—	—	—
Dick, DM et al., Archives of General Psychiatry, 2009, Role of GABRA2 in trajectories of externalizing behavior across development and evidence of moderation by parental monitoring	19487630	10.1001/archgenpsychiatry.2009.48	Cited
Dick, DM et al., Behavior Genetics, 2006, The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages	16557364	10.1007/s10519-005-9041-8	Primary
Dick, DM et al., Journal of Studies on Alcohol, 2006, Marital status, alcohol dependence, and GABRA2: Evidence for gene-environment correlation and interaction	16562401	10.15288/jsa.2006.67.185	Primary
Dick, DM et al., Perspectives on Psychological Science, 2015, Candidate gene-environment interaction research: Reflections and recommendations	25620996	10.1177/1745691614556682	Primary
Dick, DM, Annu Rev Clin Psychol, 2011, Gene-environment interaction in psychological traits and disorders	21219196	10.1146/annurev-clinpsy-032210-104518	Primary
Dodge, KA et al., Child Development, 1994, Socialization mediators of the relation between socioeconomic status and child conduct problems	8013245	10.1111/j.1467-8624.1994.tb00774.x	Cited
Edenberg, HJ et al., American Journal of Human Genetics, 2004, Variations in GABRA2, encoding the α2 subunit of the GABA-A receptor are associated with alcohol dependence and with brain oscillations	15024690	10.1086/383283	Primary
Enoch, MA et al., Biological Psychiatry, 2010, The influence of GABRA2, childhood trauma, and their interaction on alcohol, heroin, and cocaine dependence	19833324	10.1016/j.biopsych.2009.08.019	Cited
Enoch, MA et al., Neuropsychopharmacology, 2009, GABRG1 and GABRA2 as independent predictors for alcoholism in two populations	18818659	10.1038/npp.2008.171	Cited
Enoch, MA, Pharmacology, Biochemistry and Behavior, 2008, The role of GABA(A) receptors in the development of alcoholism	18440057	10.1016/j.pbb.2008.03.007	Cited
Feder, A et al., Nature Reviews Neuroscience, 2009, Psychobiology and molecular genetics of resilience	19455174	10.1038/nrn2649	Cited
Fehr, C et al., Psychiatric Genetics, 2006, Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis	16395124	10.1097/01.ypg.0000185027.89816.d9	Cited
Frick, PJ et al., The antisocial process screening device, 2001	—	—	—
Frojd, S et al., Nordic Journal of Psychiatry, 2009, Significance of family life events in middle adolescence: A survey on Finnish community adolescents	19012055	10.1080/08039480802533754	Cited
Herts, KL et al., Journal of Abnormal Child Psychology, 2012, Emotion dysregulation as a mechanism linking stress exposure to adolescent aggressive behavior	22466516	10.1007/s10802-012-9629-4	Cited
Hicks, BM et al., Archives of General Psychiatry, 2004, Family transmission and heritability of externalizing disorders - A twin-family study	15351771	10.1001/archpsyc.61.9.922	Cited
Hicks, BM et al., Archives of General Psychiatry, 2009, Environmental adversity and increasing genetic risk for externalizing disorders	19487629	10.1001/archgenpsychiatry.2008.554	Cited
Hoffmann, JP et al., Addiction, Parental substance use disorder, mediating variables and adolescent drug use: a non-recursive model	9926541	10.1046/j.1360-0443.1998.93913516.x	Cited
Hoffmann, JP et al., Substance Use & Misuse, Stressful life events and adolescent substance use and depression: Conditional and gender differentiated effects	9758012	10.3109/10826089809056256	Cited
Howie, BN et al., PLoS Genetics, 2009, A flexible and accurate genotype imputation method for the next generation of genome-wide association studies	19543373	10.1371/journal.pgen.1000529	Cited
Hussong, AM et al., Journal of Abnormal Child Psychology, 2010, Parent Alcoholism Impacts the Severity and Timing of Children’s Externalizing Symptoms	20084453	10.1007/s10802-009-9374-5	Cited
Hussong, AM et al., Journal of Abnormal Psychology, 2007, Externalizing symptoms among children of alcoholic parents: Entry points for an antisocial pathway to alcoholism	17696709	10.1037/0021-843x.116.3.529	Cited
Irons, DE et al., Alcohol Clin Exp Res, 2014, Gamma-aminobutyric Acid system genes-no evidence for a role in alcohol use and abuse in a community-based sample	24460875	10.1111/acer.12352	Cited
Kaprio, J et al., Twin Research, 2002, Genetic and environmental factors in health-related behaviors: Studies on Finnish twins and twin families	12537860	10.1375/twin.5.5.366	Cited
Keller, MC, Biological Psychiatry, 2014, Gene x environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution	24135711	10.1016/j.biopsych.2013.09.006	Cited
Kendler, KS et al., Nature Neuroscience, 2012, Recent advances in the genetic epidemiology and molecular genetics of substance use disorders	22281715	10.1038/nn.3018	Cited
Kim, KJ et al., Child Development, 2003, Reciprocal influences between stressful life events and adolescent internalizing and externalizing problems	12625440	10.1111/1467-8624.00525	Cited
Klahr, AM et al., Psychological Bulletin, 2014, Elucidating the etiology of individual differences in parenting: A meta-analysis of behavioral genetic research	24016230	10.1037/a0034205	Cited
Knaapila, A et al., Behavior Genetics, 2011, Food neophobia in young adults: genetic architecture and relation to personality, pleasantness and use frequency of foods, and body mass index: A twin study	20953688	10.1007/s10519-010-9403-8	Cited
Krueger, RF et al., Journal of Abnormal Psychology, 2002, Etiological connections among substance dependence, antisocial behavior, and personality: Modeling the externalizing spectrum	12150417	10.1037//0021-843X.111.3.411	Cited
Laucht, M et al., Biological Psychiatry, 2009, Impact of psychosocial adversity on alcohol intake in young adults: moderation by the LL genotype of the serotonin transporter polymorphism	19358979	10.1016/j.biopsych.2009.02.010	Cited
Laucht, M et al., International Journal of Neuropsychopharmacology, 2009, Interaction between the 5-HTTLPR serotonin transporter polymorphism and environmental adversity for mood and anxiety psychopathology: evidence from a high-risk community sample of young adults	19154632	10.1017/s1461145708009875	Cited
MacKinnon, DP et al., Psychological Methods, 2002, A comparison of methods to test mediation and other intervening variable effects	11928892	10.1037/1082-989X.7.1.83	Cited
Malone, SM et al., Journal of Child Psychology and Psychiatry, 2010, Mothers’ maximum drinks ever consumed in 24 hours predicts mental health problems in adolescent offspring	20085606	10.1111/j.1469-7610.2010.02219.x	Cited
Marchini, J et al., Nature Reviews Genetics, 2010, Genotype imputation for genome-wide association studies	20517342	10.1038/nrg2796	Cited
Muller, D et al., Journal of Personality and Social Psychology, 2005, When moderation is mediated and mediation is moderated	16393020	10.1037/0022-3514.89.6.852	Cited
Neumann, C et al., Journal of Research in Personality, 2011, Stability and invariance of psychopathic traits from late adolescence to young adulthood	21572537	10.1016/j.jrp.2010.12.003	Cited
Newman, DL et al., Journal of Consulting and Clinical Psychology, 1996, Psychiatric disorder in a birth cohort of young adults: Prevalence, comobidity, clinical significance, and new case incidence from ages 11–21	8698949	10.1037/0022-006X.64.3.552	Cited
Odgers, CL et al., Development and Psychopathology, 2008, Female and male antisocial trajectories: From childhood origins to adult outcomes	18423100	10.1017/s0954579408000333	Cited
Patterson, GR, Coercive family process, 1982	—	—	—
Perry, BL et al., Behavior Genetics, 2013, Gender-specific gene-environment interaction in alcohol dependence: the impact of daily life events and GABRA2	23974430	10.1007/s10519-013-9607-9	Primary
Petersen, IT et al., Development & Psychopathology, Describing and predicting developmental profiles of externalizing problems from childhood to adulthood	25166430	10.1017/S0954579414000789	Cited
Pillow, DR et al., Journal of Community Psychology, 1998, Using cluster analysis to assess the effects of stressful life events: Probing the impact of parental alcoholism on child stress and substance use	—	10.1002/(sici)1520-6629(199807)26:4<361::aid-jcop5>3.3.co;2-i	Cited
Pinheiro, J et al., Linear and nonlinear mixed effects models, 2014	—	—	—
Pitkanen, T et al., Addiction, 2008, A developmental approach to alcohol drinking behaviour in adulthood: a follow-up study from age 8 to age 42	18426540	10.1111/j.1360-0443.2008.02176.x	Cited
Porjesz, B et al., Proceedings of the National Academy of Sciences, 2002, Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus	11891318	10.1073/pnas.052716399	Primary
Pulkkinen, L et al., Twin Research, 1999, Peers, teachers and parents as assessors of the behavioural and emotional problems of twins and their adjustment: The Multidimensional Peer Nomination Inventory	10723806	10.1375/136905299320565762	Cited
R: A language and environment for statistical computing, 2014	—	—	—
Schmid, B et al., International Journal of Neuropsychopharmacology, 2010, Interacting effects of CRHR1 gene and stressful life events on drinking initiation and progression among 19-year-olds	19607758	10.1017/S1461145709990290	Cited
Selya, AS et al., Frontiers in Psychology, 2012, A practical guide to calculating Cohen’s f(2), a measure of local effect size, from PROC MIXED	22529829	10.3389/fpsyg.2012.00111	Cited
Selzer, ML et al., Journal of Studies on Alcohol, 1975, A self-administered Short Michigan Alcoholism Screening Test (SMAST)	238068	10.15288/jsa.1975.36.117	Cited
Shanahan, MJ et al., Journals of Gerontology Series B-Psychological Sciences and Social Sciences, 2005, Social context in gene-environment interactions: retrospect and prospect	15863711	10.1093/geronb/60.Special_Issue_1.65	Cited
Sher, KJ et al., Journal of Studies on Alcohol, 1997, The role of childhood stressors in the intergenerational transmission of alcohol use disorders	9203123	10.15288/jsa.1997.58.414	Cited
Spencer, CC et al., PLoS Genetics, 2009, Designing genome-wide association studies: sample size, power, imputation, and the choice of genotyping chip	19492015	10.1371/journal.pgen.1000477	Cited
Thornberry, TP et al., Journal of Abnormal Child Psychology, 2003, Linked lives: The intergenerational transmission of antisocial behavior	12735399	10.1023/A:1022574208366	Cited
Timmermans, M et al., Psychological Medicine, 2010, The role of stressful events in the development of behavioural and emotional problems from early childhood to late adolescence	20056023	10.1017/s0033291709992091	Cited
Torvik, FA et al., BMC Public Health, 2011, Parental alcohol use and adolescent school adjustment in the general population: Results from the HUNT study	21929803	10.1186/1471-2458-11-706	Cited
Tremblay, RE, Journal of Child Psychology and Psychiatry, 2010, Developmental origins of disruptive behaviour problems: the ‘original sin’ hypothesis, epigenetics and their consequences for prevention	20146751	10.1111/j.1469-7610.2010.02211.x	Cited
Verlaan, P et al., International Journal of Behavioral Development, 2002, Mother’s and father’s parental adjustment: Links to externalising behaviour problems in sons and daughters	—	10.1080/01650250042000717	Cited
Villafuerte, S et al., Brain Behav, 2014, Genetic variation in moderates peer influence on externalizing behavior in adolescents	25365806	10.1002/brb3.291	Cited
Villafuerte, S et al., Molecular Psychiatry, 2012, Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism	21483437	10.1038/mp.2011.33	Cited
Wills, TA et al., Current Directions in Psychological Science, 2003, Family factors and adolescent substance use: Models and mechanisms	—	10.1046/j.0963-7214.2003.01266.x	Cited
Wills, TA et al., Developmental Psychology, 2001, Family risk factors and adolescent substance use: Moderation effects for temperament dimensions	11370906	10.1037/0012-1649.37.3.283	Cited
Windle, M et al., Journal of Abnormal Psychology, 1996, Coping strategies, drinking motives, and stressful life events among middle adolescents: Associations with emotional and behavioral problems and with academic functioning	8952188	10.1037//0021-843x.105.4.551	Cited
Windle, M, Developmental Psychology, 1992, A Longitudinal study of stress buffering for adolescent problem behaviors	—	10.1037//0012-1649.28.3.522	Cited
Zintzaras, E, Psychiatric Genetics, 2012, Gamma-aminobutyric acid A receptor, alpha-2 (GABRA2) variants as individual markers for alcoholism: a meta-analysis	22555154	10.1097/YPG.0b013e328353ae53	Cited

In this knowledge base

Title	Year	PMID
A genome wide association study of fast beta EEG in families of European ancestry.	2017	28040410
An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry.	2017	28070124
Genetic influences on adolescent behavior.	2016	27422449

External

Title	Authors	Journal	Year	Link
Genetics of child aggression, a systematic review.	Koyama E et al.	—	2024	→
Intergenerational transmission of psychopathology: An examination of symptom severity and directionality.	Marceau K et al.	—	2022	→
Academic performance, externalizing disorders and depression: 26,000 adolescents followed into adulthood.	Sörberg Wallin A et al.	—	2019	→
FinnTwin12 Cohort: An Updated Review.	Rose RJ et al.	—	2019	→
Intergenerational continuity in alcohol misuse: Maternal alcohol use disorder and the sequelae of maternal and family functioning.	Johnson AK et al.	—	2019	→
The influence of parental offending on the continuity and discontinuity of children's internalizing and externalizing difficulties from early to middle childhood.	Whitten T et al.	—	2019	→
Development of aggression.	Lansford JE	—	2018	→
A genome wide association study of fast beta EEG in families of European ancestry.	Meyers JL et al.	—	2017	→
An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry.	Meyers JL et al.	—	2017	→
Stressful life events increase aggression and alcohol use in young carriers of the GABRA2 rs279826/rs279858 A-allele.	Kiive E et al.	—	2017	→
Genetic influences on adolescent behavior.	Dick DM et al.	—	2016	→