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. 2021 Apr 1;11:197. doi: 10.1038/s41398-021-01300-2

Table 6.

Detailed characteristics of studies investigating offspring substance use behaviours (N = 19).

Offspring substance use behaviours
Study Design Sample Parental attribute (predictor) Child attribute (outcome) Control variables Genetic overlap Environmental transmission G–E interplay
McGue et al.106 Adoption

SIBS

409 adoption and 208 biological families

Age: 10–28 years

Drinking behaviour: self-report, composite score, CSUA and SAM Drinking behaviour: self-report, composite score, CSUA and SAM Parent gender, and child gender Not studied Yes, adoptive parent drinking behaviour was associated with offspring drinking behaviour Passive rGE implied: parent–offspring association was greater in biological pairs than adoptive pairs
Waldron et al.94 Children-of-twins

MATCH, PACER

1318 offspring of twin parents

Age: 11–24 years

Substance dependence: self-report, SAGA

Parental separation: study design cannot distinguish G and E effects

Offspring substance involvement: self-report, SAFA Parent or offspring comorbid psychopathology, twin sex, twin age, twin EA, child sex, age Substance dependence: yes, there were shared genetic effects between parental substance dependence and offspring substance involvement (effect size not clear) Substance dependence: after accounting for genetic relatedness, parental substance dependence was not associated with offspring substance involvement with the exception of cannabis use which was associated with offspring smoking behaviour (effect size not clear)
Kuja-Halkola et al.67 Sibling comparison, children-of-twins

Snr

2,754,626 children

Age: up to 20 years

Maternal smoking during pregnancy: self-report Drug/alcohol misuse: register-based, diagnosis, or drug-related conviction Maternal age at childbirth, child sex, birth year Yes, there were shared genetic effects between maternal smoking during pregnancy and offspring drug/alcohol misuse (effect size not clear) No, exposed children did not differ from their unexposed siblings, and after accounting for genetic relatedness, maternal smoking was not associated with offspring drug/alcohol misuse
Kendler et al.95 Adoption

Snr

18,115 adoptees, 171,989 not-lived-with parent, and 107,699 step-parent families

Mean age: 33.9 years

AUD: Swedish Hospital Discharge Register, the Swedish Prescribed Drug Register, the Outpatient Care Register, the Primary Health Care Register, and the Swedish Crime and Suspicion Register AUD: Swedish Hospital Discharge Register, the Swedish Prescribed Drug Register, the Outpatient Care Register, the Primary Health Care Register, and the Swedish Crime and Suspicion Register Yes, birth parent AUD predicted offspring AUD (OR = 1.46) Yes, adoptive parent AUD predicted offspring AUD (OR = 1.40) No G × E interaction observed
Grant et al.96 Children-of-twins

VET

1828 offspring of male twin parents

Age: not reported

Parental alcohol or drug dependency: diagnosis, DIS

Parental separation: study design cannot distinguish G and E effects

Alcohol involvement: self-report, SAGA Maternal alcohol dependency, heavy cannabis use, family income, child sex, age, history of psychiatric problems and traumatic life events, inattention, hyperactivity and oppositional defiant disorder Substance dependency: yes, there were shared genetic effects between parental substance dependence and offspring alcohol involvement (effect size not clear) Substance dependency: yes, after accounting for genetic relatedness, parental substance dependency was associated with offspring alcohol involvement (effect size not clear)
Kendler et al.8 Triparental family design

Snr

41,360 triparental families (mother, not-lived-with biological father, and stepfather)

Age: 15+

Drug abuse: medical registries, the Crime Register, the Suspicion Register, drug-related driving offences, and the Prescribed Drug Register

AUD: medical and mortality registries, the Suspicion Register, the Crime Register, and the Prescribed Drug Register

Drug abuse: medical registries, the Crime Register, the Suspicion Register, drug-related driving offences, and the Prescribed Drug Register

AUD: medical and mortality registries, the Suspicion Register, the Crime Register, and the Prescribed Drug Register

Yes, drug abuse and AUD registration of not-lived-with biological parents were correlated with offspring drug abuse and AUD (HR range = 1.84–2.45) Yes, drug abuse or AUD registration of adoptive or step-parent correlated with offspring drug abuse or AUD (HR range = 1.27–1.99)
Kendler et al.98 Triparental family design

Snr

2,111,074 offspring in intact families 155,121 not-lived-with father, 10,194 not-lived-with mother, 107,163 stepfather, 17,637 stepmother 10,038 adoptive families

Age: 15+

Drug abuse: medical registers, the Crime Register, the Suspicion Register, and drug-related driving offences Drug abuse: medical registers, the Crime Register, the Suspicion Register, and drug-related driving offences Drug abuse status of all other relevant biological and step-parents Yes, drug abuse behaviour of not-lived-with biological parents were correlated with offspring drug abuse (HR = 2.73) Yes, drug abuse behaviour of adoptive or step-parent correlated with offspring drug abuse (HR = 1.79)
Bidwell et al.105 Sibling comparison

MO-MATCH

173 mothers and their offspring

Age: 7–15 years

Smoking during pregnancy: self-report, MAGIC-PC Substance use: self-report, DUSI Maternal age, marital status, EA, qualification for food stamps at the time of delivery, parental substance use outside of pregnancy, childbirth order, sex, exposure to paternal smoke during pregnancy Not studied No difference in substance use behaviours between exposed children and their unexposed siblings
Kendler et al.97 Extended family design

Snr

38,373 offspring of not-lived-with fathers and 9711 offspring of step-fathers

Age: 15+

AUD: medical registries, the Prescribed Drug Register, two or more convictions of drunk driving in the Crime register AUD: medical registries, the Prescribed Drug Register, two or more convictions of drunk driving in the Crime register AUD in the biological mother, and offspring sex Yes, not-lived with father AUD (including age of registration, recurrence and number of AUD registrations) predicted offspring AUD (HR not reported) Yes, stepfather AUD (including the number of registrations that occurred while co-offspring with offspring) predicted offspring AUD (HR = 1.03)
Treur et al.100 Children-of-twins, within-family PGS: genetic sensitivity analysis

NTR

CoT sample: 712 twins, 723 children

PGS sample: 4072 individuals

Age: not reported

Smoking initiation (CoT sample): self-report

Exposure to smoking (PGS sample): offspring-reported exposure as a child (up to age 18)

CoT sample smoking initiation: self-report

PGS sample smoking behaviour: self-report, smoking initiation and smoking heaviness

CoT: twin sex, twin age, child sex, age, family-based clustering correction

PGS: sex, year of birth, ten principal components, family clustering correction

CoT sample: yes, there were shared genetic effects between parent and offspring smoking initiation (effect size not clear)

PGS sample: not studied

CoT sample: yes, after accounting for genetic relatedness, parent smoking initiation was associated with offspring smoking initiation (effect size not clear)

PGS sample: yes, after adjusting for smoking PGS, exposure to smoking during childhood was associated with smoking initiation (OR = 1.68)

G×E: high PGS for smoking initiation & heaviness × childhood exposure to smoking: smoking heaviness (no interaction for smoking initiation)
Maes et al.103 Extended twin

V-30, A-25 22,393 twins and their families

Age: 18+

Smoking initiation: self-report Smoking initiation: self-report Age Not studied There were shared environmental effects underlying parent–offspring similarity in smoking initiation (negative cultural transmission) Passive rGE: negative covariance between additive genetic effects and parental smoking
Kendler et al.99 Multiple parenting relationships design

Snr

2,111,074 intact, 41,360 triparental, 113,762 not-lived-with father, 10,194 not-lived-with mother, 65,803 stepfather, 17,637 stepmother, 10,038 adoptive families

Age: not reported

Drug abuse: medical and mortality registries, the Suspicion and Crime registers, drug-related driving offences, and the Prescribed Drug Register Drug abuse: medical and mortality registries, the Suspicion and Crime registers, drug-related driving offences, and the Prescribed Drug Register Yes, drug abuse behaviour of not-lived-with biological parents were correlated with offspring drug abuse (r range = 0.13–0.19) Yes, drug abuse behaviour of adoptive or step-parent correlated with offspring drug abuse (r range = 0.06–0.09)
Kendler et al.11 Matched-pairs case–control

Snr

65,006 parent–offspring, sibling, and cousin pairs

Age: 19–23 years

Drug abuse: medical registers, the Crime Register, the Suspicion Register, and drug-related driving offences Drug abuse: medical registers, the Crime Register, the Suspicion Register, and drug-related driving offences in offspring whose parents had a drug abuse incident 1–3 years ago Control parent–child pairs matched on sex, parent and child year of birth, country of birth, SES, number of lifetime drug abuse registrations, medical or criminal registration, parental EA Not studied Yes, exposed offspring were at increased risk of drug abuse than matched control offspring who were unexposed to parental drug registration
Kendler et al.9 Multiple parenting relationships design

Snr

475,000 parent–offspring pairs

Age: 15 and over

Drug abuse: medical registries, the Crime Register, the Suspicion Register, drug-related driving offences, and the Prescribed Drug Register

AUDs: medical and mortality registries, the Suspicion Register, the Crime Register, and the Prescribed Drug Register

Drug abuse: medical registries, the Crime Register, the Suspicion Register, drug-related driving offences, and the Prescribed Drug Register

AUDs: medical and mortality registries, the Suspicion Register, the Crime Register, and the Prescribed Drug Register

Drug abuse or AUD status of all other relevant biological and step-parents, offspring year of birth, and offspring sex Yes, drug abuse and AUD registration of not-lived-with biological parents were correlated with offspring drug abuse and AUD (r range = 0.14–0.16) Yes, drug abuse or AUD registration of adoptive or step-parent correlated with offspring drug abuse or AUD (r range = 0.04–0.10)
Kendler et al.102 Extended family design

Snr

44,250 children of high-risk parents (affected with drug abuse), and offspring of discordant sibling or sibling-in-law

Age: 15 and over

Drug abuse and alcohol use disorder: medical registries, the Crime Register, the Suspicion Register, drug-related driving offences, and the Prescribed Drug Register

Criminal behaviour: Swedish Crime register

Psychiatric registration: any mental disorder

Drug abuse: medical registers, the Crime Register, the Suspicion Register, drug-related driving offences, and the Prescribed Drug Register Child sex, year of birth Not studied Yes, after accounting for genetic relatedness, parent (and step-parent) drug abuse, AUD, criminal behaviour and psychiatric registration was associated with offspring drug abuse
Cea & Barnes108 Adoption

VFS

328 biological and 77 adoption families

Age: 14–33 years

Parenting styles: offspring report, family cohesion (FACES-II), mother & father care, mother & father overprotectiveness (PPBI), parental monitoring, mother and father support, mother and father control (GBF) Polysubstance use: self-report, composite score, alcohol composition (Volume-Variability Index), smoking, and other drug usage at time 1 (T1: 14–25 years) and T2 (21–33 years) Age, gender, and adoption status Not studied At T1, adoptive family cohesion, parental monitoring, maternal and paternal positive parenting, and father overprotection were associated with offspring substance use (maternal and paternal coercion, maternal overprotectiveness coercion were not). At T2, only cohesion, maternal coercion and overprotection were significant
Cea & Barnes104 Adoption

VFS

328 biological and 77 adoption families

Age: 14–33 years

Addiction-prone personality: self-report, APP-21

Familial care factor: mother, father & offspring report, PPBI and FACES-II

Addiction-prone personality: self-report, APP-21 Adoption status, and child gender Not studied Adoptive parent addiction-prone personality and familial care factor were associated with offspring addiction-prone personality
Samek et al.107 Adoption

SIBS

568 adopted and 412 biological offspring

Age: 11–25.5 years

Parental involvement: offspring report, an average of the maternal and paternal score, PEQ Substance use: self-report, CSUA Earlier substance use Not studied Yes, adoptive parental involvement was negatively associated with offspring substance use No evidence of passive rGE found
Kendler et al.109 Sibling comparison

Snr

1161 full sibships and 3085 half-sibships of high-risk biological parents; one sibling reared by biological, other by adoptive parents

Age: 15 and over

Adoptive parenting: protective effect of high-quality rearing environment Drug abuse: medical registers, the Suspicion Register, the Crime Register, drug-related driving offences, and the Prescribed Drug Register Parental age at birth, high-risk status of the other parent of half-sibling, child gender Not studied Children exposed to adoptive parenting had a lower risk of drug abuse than their unexposed siblings, this protective effect disappeared when the adoptive family was disrupted or if there was a high-risk adoptive parent

G–E gene–environment, G×E gene–environment interaction, rGE gene–environment correlation.

Design = PGS Polygenic scores.

Samples = A-25 Australia 25,000 study, MATCH Mothers and Their Children Study, MO-MATCH Missouri Mothers and Their Children Study, PACER Parent Alcoholism and Child Environmental Risk Study, SIBS Sibling Interaction and Behaviour Study, Snr Swedish National Registers, VET Vietnam Era Twin Registry, VFS Vancouver Family Survey, V-30 Virginia 30,000 study.

Measures = APP-21 Addiction-Prone Personality-21 Scale, CSUA Computerised Substance Use Assessment, DIS Diagnostic Interview Schedule, DUSI revised Drug Use Screening Inventory, FACES-II Family Adaptability and Cohesion Evaluation Scales II, GBF Grace Barnes and Farrell’s 1982 Study, MAGIC-PC Missouri Assessment of Genetics Interview for Children–Parent on Child, PEQ Parental Environment Questionnaire, PPBI Parker Parenting Bonding Instrument, SAGA Semi-structured Assessment of the Genetics of Alcoholism.

Statistics = OR odds ratio, HR hazard ratio, r weighted tetrachoric correlation. Effect sizes are not reported for studies that did not investigate both genetic and environmental transmission.