American Journal of Medical Genetics (Neuropsychiatric Genetics) 88:391–397 (1999)

Interrelationship of Genetic and Environmental

Influences on Conduct Disorder and Alcohol and
Marijuana Dependence Symptoms
William R. True,1,2* Andrew C. Heath,3 Jeffrey F. Scherrer,1,2 Hong Xian,2,4 Nong Lin,2,4
Seth A. Eisen,4,5 Michael J. Lyons,6,7 Jack Goldberg,9 and Ming T. Tsuang6,8
1
School of Public Health, St. Louis University Health Sciences Center, St, Louis, Missouri
2
Research Service, St. Louis VAMC, St. Louis, Missouri
3
Departments of Psychiatry, Psychology, and Genetics, Washington University School of Medicine, St. Louis, Missouri
4
Department of Internal Medicine, Division of General Medical Sciences, Washington University School of Medicine,
St. Louis, Missouri
5
Research Service and Medical Service, St. Louis VAMC, St. Louis, Missouri
6
Harvard Medical School, Department of Psychiatry at Brockton/West Roxbury VAMC, Brockton, Massachusetts
7
Department of Psychology, Boston University, Boston, Massachusetts
8
Harvard Institute of Psychiatric Epidemiology and Genetics, Boston, Massachusetts
9
Department of Veterans Affairs, Health Services Research and Development, Cooperative Studies in Health Services,
Hines, Illinois, and Epidemiology Program, School of Public Health, University of Illinois, Chicago, Illinois

Data from the Vietnam Era Twin (VET) Reg-
istry were analyzed to explore the degree to
which the same genetic and environmental
factors contribute to childhood conduct dis-
order symptoms and to alcohol and mari-
juana dependence symptoms. Data on con-
duct disorder and alcohol and marijuana
dependence were obtained from adminis-
tration of the Diagnostic Interview Sched-
ule to 1,856 monozygotic and 1,479 dizygotic
male-male twin pair members of the VET
Registry. Multivariate genetic models were
compared to determine the genetic and en-
vironmental influences common and or spe-
cific to all three phenotypes. A full model
that allowed for common genetic and envi-
ronmental influences to all three pheno-
types gave a good fit to the data, but the best
fitting reduced model did not allow for a ge-
netic influence on conduct disorder symp-
Contract grant sponsor: Department of Veterans Affairs Health
Services Research and Development Service Std, 992; Contract
grant sponsor: NIDA; Contract grant number: 1 RO1 DAO 4604-
01; Contract grant sponsor: NIAAA; Contract grant number: 1
RO1 AA10339-01; Contract grant sponsor: Great Lakes Veterans
Affairs Health Services Research and Development Program;
Contract grant number: LIP 41-065; Contract grant sponsor: Pub-
lic Health Service; Contract grant numbers: MH-37685, MH-
31302; Contract grant sponsor: NIDA; Contract grant number:
DAO72261-01.
*Correspondence to: William R. True, Ph.D., M.P.H., VAMC-St.
Louis Research Service 151-JC, 915 North Grand Blvd, St. Louis,
MO 63106. E-mail: True@SLU.EDU
Received 17 March 1998; Accepted 10 December 1998
© 1999 Wiley-Liss, Inc.
toms. Under the best fitting reduced model,
genes explained 44.7% of the variance in
risk for alcohol dependence symptoms. The
genetic liability for symptoms of marijuana
dependence was due to a 36.3% specific con-
tribution and a 7.6% contribution from
genes common with alcohol dependence
symptoms. Family environmental contribu-
tions common to all three phenotypes ex-
plained 46.7%, 11.9%, and 21.3% of variance
in risk for symptoms of conduct disorder,
alcohol dependence, and marijuana depen-
dence, respectively. Common family envi-
ronmental factors contribute to risk of con-
duct disorder symptoms and alcohol and
marijuana dependence symptoms. Common
genetic influences contribute to risk of
symptoms of alcohol dependence and mari-
juana dependence. While our findings sug-
gest genes do not contribute to co-morbid
conduct disorder symptoms, comparisons
with other twin studies suggest that the role
of genes in risk for conduct disorder re-
mains uncertain. Am. J. Med. Genet. (Neuro-
psychiatr. Genet.) 88:391–397, 1999.
© 1999 Wiley-Liss, Inc.
KEY WORDS: genes; psychopathology; sub-
stance abuse
INTRODUCTION
Conduct disorder (CD) and substance dependence of-
ten occur together. This is particularly striking for al-
392 True et al.
cohol and marijuana, which are often the first sub-
stances of abuse (other than tobacco) reported in CD
[Young et al., 1995]. Since adolescents with conduct
disorder may be more likely to develop substance use
problems, the familial contributions to CD may also
increase risk for drug problems. Characterizing the re-
lationship among CD, alcohol dependence (AD), and
marijuana dependence (MJ) may allow for better iden-
tification of individuals most vulnerable, thereby con-
tributing to optimized prevention and treatment of CD-
substance abuse co-morbidity.
Accumulating research in both humans and animals
supports the concept that genetic and environmental
factors play important roles in the development of sub-
stance abuse [Grove et al., 1990; Chen et al., 1991;
Pickens et al., 1991; Crabbe et al., 1994; Cadoret et al.,
1995]. Animal studies have found strain-specific re-
sponses to the rewarding properties of marijuana
[Chen et al., 1991]. Studies of the heritability of sub-
stance abuse in humans have included a range of ap-
proaches from adoption models [Cadoret et al., 1995],
separated twin models [Grove et al., 1990], and identi-
cal and fraternal twin concordance studies [Pickens et
al., 1991]. Findings from previous analysis of the Viet-
nam Era Twin (VET) data set suggest that genes ac-
count for approximately one-third of the variance in
risk for MJ abuse [Tsuang et al., 1996]. Study of the
heritability of AD has a long history and several twin
projects have estimated the genetic contribution to al-
cohol abuse and/or dependence. Kendler and colleagues
[1997] recently reported that 54% of the risk of tem-
perance board registration in a Swedish twin popula-
tion was due to genes. We have estimated a 55% ge-
netic contribution to risk of AD in male-male twin
members of the VET Registry [True et al., 1996].
Compared with drug abuse, the familial contribution
to CD is less well understood since current research
has not resolved the relative impact of genes or envi-
ronment to risk of developing the disorder. In a previ-
ous study of VET Registry twins, model fitting found
juvenile antisocial traits (analogous to CD symptoms)
to be only slightly heritable, with genes accounting for
7% and family environmental influences accounting for
31% of the variance in juvenile antisocial traits [Lyons
et al., 1995]. The finding in the VET Registry twins,
however, is not consistent with the analysis of data
from the Australian Twin study, which found CD was
due to a large 71% genetic contribution with no signifi-
cant family environmental influence [Slutske et al.,
1997]. The results from other research suggests both
genes and the family environment contribute to CD.
For example, adoptee aggression has been attributed to
a gene-environment interaction [Cadoret et al., 1995],
and a review of twin and family studies implicated both
environmental influences, genetic transmission and in-
teraction [Lytton, 1990]. Although the extant literature
is inconclusive regarding the magnitude of the genetic
contribution to CD, the weight of evidence supports a
role for familial influences.
Both environmental and genetic factors play impor-
tant roles in the comorbidity of CD with AD and MJ
[Buckstein et al., 1989; DeMilio, 1989; Vulcano, et al.,
1990; Johnson and Pandina, 1991]. McGue et al. [1992]
found that identical twin brothers of alcoholic probands
were at increased risk of CD, which suggests a common
familial contribution to CD and alcoholism. Likewise, a
study of adoptees found evidence for the co-inheritance
of alcohol abuse/dependence with adoptee aggression
[Cadoret et al., 1995]. These authors identified a path-
way to substance abuse in which antisocial personality
in biologic parents of adoptees leads eventually to
adoptee CD, antisocial personality, and substance
abuse/dependence.
The co-occurrence of CD with AD and with MJ raises
critical issues about influences that are shared or
unique to conduct problems and substance use disor-
ders. Presently, little is known about common additive
genetic and environmental factors contributing to the
lifetime co-occurrence of CD symptoms, AD symptoms,
and MJ symptoms. To our knowledge there are no re-
ports of the common factors contributing to all three
phenotypes.
We analyzed telephone interview data collected from
members of the VET Registry to address whether there
are additive genetic influences to symptoms of AD and
MJ that also contribute to development of CD symp-
toms. These symptoms of AD and MJ represent the
most common illicit substance use in adolescent psy-
chopathology [Hovens et al., 1994]. Earlier univariate
analyses of each phenotype suggested the importance
of investigating the degree to which genetic and/or en-
vironmental factors are common to symptoms of CD,
AD, and MJ.
MATERIALS AND METHODS
Sample
The VET Registry, consisting of 7,375 male-male
twin pairs born between 1939 and 1955 in which both
siblings served on active military duty during the Viet-
nam era (1965–1975), was derived from a Department
of Defense computer tape of 5.5 million Vietnam veter-
ans. Twins were first identified by matching veterans
for same last name, date of birth, and similar social
security number, then confirmed by examination of
military service records. Zygosity was assigned using
responses to a series of questions about similarity of
physical appearance, supplemented with blood group
typing information. A complete description of the Reg-
istry construction [Eisen et al., 1987] and method of
zygosity determination [Eisen et al., 1989] was previ-
ously published.
In 1992, approximately 5,000 twin pairs of the VET
Registry, who had participated in a 1987 research proj-
ect, were invited to respond to a telephone administra-
tion of the Diagnostic Interview Schedule, Version III,
Revised (DIS3R) [Robins et al., 1981]. Data collected
from the DIS3R was used to derive psychiatric diag-
noses and individual symptoms according to Diagnostic
and Statistical Manual of Mental Disorders (DSM-III-
R) criteria [APA, 1987].
After trained interviewers from the Institute for Sur-
vey Research contacted the twins, the study was de-
scribed, verbal informed consent was obtained, and in-
terviewing began. Respondents were asked questions
regarding their use of drugs including alcohol and
marijuana, the latter inclusive of “hashish,” “bhang,”
 Genetic Influences on Conduct Disorder, Marijuana and Alcohol Dependence
and “ganja.” The interview also included questions de-
signed to identify symptoms of several psychiatric dis-
orders including childhood CD symptoms. Symptoms of
CD included stealing, running away, frequent lying,
fire-setting, truancy, breaking into others’ homes, de-
stroying others’ property, physical cruelty to animals,
forced sexual activity, use of weapons, physical fight-
ing, confrontational stealing, and physical cruelty to
others.
Lifetime symptoms of CD, AD, and MJ were derived
from a computer algorithm according to DSM-III-R cri-
teria [APA, 1987]. For model fitting analyses we uti-
lized the broad definitions for CD, AD, and MJ, which
included the occurrence of three or more symptoms
ever in a lifetime. In contrast, full DSM-III-R criteria
for CD requires three or more symptoms within 6
months, and full criteria for substance dependence re-
quires three or more symptoms that have persisted for
at least 1 month or recur over a longer period of time.
We performed analyses on the broad definitions of CD,
AD, and MJ because preliminary analyses revealed
that the prevalence of co-morbidity between full DSM-
III-R criteria substance dependence and CD was too
low to provide the statistical power to resolve whether
the familial contributions to CD and substance depen-
dence were genetic, environmental, or both.
Eligibility criteria for the present study were: (1)
both members of the twin pair were identified from
Department of Defense computer files [Goldberg et al.,
1987], (2) both members of the pair completed all CD
and alcohol and marijuana use questions from the tele-
phone interview, and (3) zygosity could be definitively
assigned according to the method described above. The
final analyses were performed on a sample of 3,335
twin pairs (1,856 monozygotic [MZ], 1,479 dizygotic
[DZ]).
The mean age of eligible respondents for this study
in 1992 was 42.0 years (SD ± 2.7, range 33 to 52 years);
93.8% were non-Hispanic white, 5.8% African-
American, <1.0% Hispanic, 0.3% “other”; 33.3% were
high school graduates and 38.7% college graduates;
98.2% were employed full-time and 1.8% part-time.
Statistical Analysis
A trivariate Cholesky model was fit to the data to
estimate the genetic and environmental correlations
among CD symptoms, AD symptoms, and MJ symp-
toms [Neale and Cardon, 1992]. This was equivalent to
estimating genetic, family, and unique environmental
variances for each phenotype as well as correlations
between genetic and environmental effects for each
pair of phenotypes. For trivariate modeling, a 6 × 6
tetrachoric correlation matrix was calculated for MZ
and DZ twin pairs’ CD symptoms and substance depen-
dence symptoms. This resulted in three within-
variable cross-twin correlations (CD-CD, AD-AD, MJ-
MJ), three within-twin cross-variable correlations (CD-
AD, CD-MJ, AD-MJ), and three cross-twin, cross
variable correlations (CD-AD, CD-MJ, AD-MJ).
Multivariate analysis compared the fit of the full
model (ACE) for symptoms of CD, AD, and MJ to that
of reduced models, which removed one or more genetic
393
or environmental parameters. A ␹2 difference statistic
was used to determine the best fitting model. If two or
more reduced models adequately accounted for the
data, the most parsimonious model, indicated by the
lowest Akaike’s information criterion (AIC) [Akaike,
1987], was accepted as best fitting. Detailed genetic
modeling procedures are described in Neale and Car-
don [1992]. MX software [Neale, 1991] was utilized for
the genetic modeling and PRELIS 2 [Joreskog and Sor-
bom, 1988] was utilized to compute tetrachoric and
polychoric correlations and asymptotic covariance ma-
trices. Models were fitted by asymptotic weighted least
squares.
We performed tests of the equal environments as-
sumption for each phenotype studied (CD symptoms,
AD symptoms, and MJ symptoms), by measuring the
impact of common familial environmental contribu-
tions at different levels of self-reported twin pair con-
tact or twin rated similarity and closeness [Neale and
Cardon, 1992]. For each phenotype, we found that the
variation in the impact of the specified common famil-
ial environmental contribution as a function of these
childhood closeness measures was not significant.
RESULTS
For MZ and DZ twins combined, the prevalence of
subjects reporting three or more lifetime symptoms
of CD, AD, and MJ was 7.9%, 38.3%, and 6.7% re-
spectively. Among subjects with three or more life-
time AD symptoms, 13.2% also had three or more
lifetime MJ symptoms. For those without three or
more lifetime AD symptoms only 2.7% had three
or more lifetime MJ symptoms. Among respondents
with three or more lifetime CD symptoms, 64.8% also
had three or more lifetime AD symptoms and 17.8%
also had three or more lifetime MJ symptoms. Among
persons with no history of CD, 34.8% also had three or
more lifetime symptoms of AD and 6.7% had three or
more lifetime symptoms of MJ.
The full trivariate model gave an excellent fit to the
data (␹215 ⳱ 7.31, p ⳱ 0.948, AIC ⳱ −22.69). A com-
parison of the goodness of fit of reduced models is
shown in Table I. The most parsimonious model for the
observed comorbidity of symptoms of CD, AD, and MJ,
shown in bold in Table I, gave an excellent fit to the
data (␹222 ⳱ 13.51, p ⳱ 0.918, AIC ⳱ −30.49). Though
a model that allowed for a unique environmental con-
tribution common to CD, AD, and MJ had the lowest
AIC (−31.20), this path was not significant (95% CI
0.0–0.03). Thus, we arrived at a best fitting model that
was the most economical fit for the data and was not
significantly worse than the full model (⌬␹27 ⳱ 6.20, p
> 0.10). This reduced model assumed no common ge-
netic contribution to symptoms of CD, AD, and MJ. The
model did allow for genetic influences common to symp-
toms of AD and MJ and a genetic contribution specific
to symptoms of MJ. This reduced model included fam-
ily environmental contributions that overlapped life-
time symptoms of CD, lifetime symptoms of AD, and
lifetime symptoms of MJ. Unique environmental con-
tributions under the best fitting model overlapped risk
for CD symptoms and AD symptoms and overlapped
394 True et al.

TABLE I. Results of Multivariate Model Fitting of Conduct Disorder (CD*), Alcohol Dependence (AD*), and Marijuana
Dependence (MJ*)
Additive Genetic Factor Family Environment Factor Unique Environment Factor
Common Common Spec. Common Common Spec. Common Common Spec. Fit of Model
CD - AD - MJ AD - MJ MJ CD - AD - MJ AD - MJ MJ CD - AD - MJ AD - MJ MJ df ␹2 p-value AIC
✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 15 7.31 0.948 −22.69
✓ ✓ X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 16 8.07 0.947 −23.93
✓ X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 16 9.35 0.898 −22.65
✓ ✓ ✓ ✓ ✓ X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 16 8.40 0.936 −23.60
✓ ✓ ✓ ✓ ✓ ✓ ✓ X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 16 11.50 0.778 −20.50
✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ X ✓ ✓ ✓ ✓ ✓ ✓ 16 7.31 0.967 −24.69
✓ X X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 17 9.92 0.907 −24.10
✓ ✓ X ✓ ✓ X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 17 9.07 0.938 −24.93
✓ ✓ ✓ ✓ ✓ ✓ ✓ X X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 17 14.33 0.644 −19.68
X X X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 18 10.20 0.925 −25.80
✓ X X ✓ X ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 18 15.94 0.569 −20.10
✓ ✓ ✓ ✓ ✓ ✓ ✓ X X ✓ X ✓ ✓ ✓ ✓ ✓ ✓ ✓ 18 14.46 0.699 −21.54
X X X ✓ ✓ ✓ ✓ ✓ ✓ X X X ✓ ✓ ✓ ✓ ✓ ✓ 21 10.80 0.967 −31.20
X X X ✓ ✓ ✓ ✓ ✓ ✓ X X X ✓ ✓ X ✓ ✓ ✓ 22 13.51 0.918 −30.49

*Defined as three or more symptoms in a lifetime; best fitting model shown in bold.
Abbreviations: ✓ parameter included in model, X parameter fixed to zero.

risk for AD symptoms and MJ symptoms. The model
also allowed for a unique environmental influence spe-
cific to MJ symptoms.
The variance due to additive genetic, family environ-
mental, and unique environmental effects is shown un-
der the best fitting reduced model (Fig. 1). Additive
genetic influences common to AD symptoms and MJ
symptoms were apportioned 44.7% (95% CI: 37–51%)
and 7.6% (2–13%), respectively. A disorder-specific ge-
netic contribution of 36.3% (25–47%) accounted for the
remaining genetic influence to MJ symptoms.
Family environmental influences that overlapped
risk for CD symptoms, AD symptoms, and MJ symp-
toms accounted for 46.7% (39–55%), 11.9% (7–17%),
and 21.3% (14–31%) of the variance in liability for each
phenotype, respectively. The remainder of phenotypic

Fig. 1. Percent variance and (95% CI) in risk for three or more lifetime symptoms of CD (conduct disorder), three or more lifetime symptoms of AD
(alcohol dependence) and three or more lifetime symptoms of MJ (marijuana dependence) due to genetic (A), family environmental (C), and unique
environmental (E) factors under the best fitting multivariate twin model.
 Genetic Influences on Conduct Disorder, Marijuana and Alcohol Dependence
variance for symptoms of CD, AD, and MJ was due to
unique environmental effects. These unique environ-
mental effects were common to CD and AD symptoms
and common to AD and MJ symptoms. Risk for MJ
symptoms was also influenced by a unique environ-
mental influence specific to this disorder.
DISCUSSION
In this sample of VET Registry twins, results indi-
cated the associations of three or more lifetime symp-
toms, respectively, of CD, of AD, and of MJ are largely
explained by family environmental influences common
to all three phenotypes. The fit of a full model, allowing
for genetic and family environmental influences com-
mon to CD symptoms, AD symptoms, and MJ symp-
toms, was not significantly different from a reduced
model with no genetic contribution to CD symptoms.
The most parsimonious explanation for the observed
lifetime co-occurrence of CD symptoms, AD symptoms,
and MJ symptoms allowed for genetic contributions
that were common to AD symptoms and MJ symptoms.
This model also included family environmental influ-
ences common to CD symptoms, AD symptoms, and MJ
symptoms, but no genetic influence to CD symptoms.
We found unique environmental influences common to
lifetime CD symptoms and lifetime AD symptoms.
Unique environmental influences were also common to
lifetime AD symptoms and lifetime MJ symptoms with
a residual unique environmental influence to MJ
symptoms.
Our findings suggest that the lifetime co-occurrence
of CD symptoms, AD symptoms, and MJ symptoms are
influenced by family environmental factors common to
all three phenotypes, and might occur if the same en-
vironmental factors influence risk for symptoms of CD,
AD, and MJ. Another possible explanation for common
family environmental effects may originate from envi-
ronmental factors initially influencing the develop-
ment of CD symptoms that encouraged exposure to and
subsequent development of symptoms of AD and MJ.
These alternatives are reflected in studies by Boyle et
al. [1992], who found that early adolescent CD pre-
dicted use of marijuana and other drugs in late adoles-
cence while attention deficit disorder and emotional
disorder did not. Previous research on the heritability
of co-morbid CD and AD suggests there are familial
influences common to both disorders [McGue et al.,
1992; Merikangas et al., 1985], which may be due to
a family environmental contribution common to CD
and AD.
In recent reviews, the relationship of genetics, envi-
ronment, and CD has been described. Several studies
have focused on parental influences. Lytton [1990] hy-
pothesized that genetic factors may be passed from an-
tisocial parents to the child, who also develops in a
pathological family environment. Rutter [1994] offers a
bi-directional influence on CD where deviant behavior
creates family discord that fosters a home environment
which stimulates CD symptoms. Some prior research
suggests that the association of parental antisocial be-
havior with childhood CD is evidence for a common
genetic component, while other work implies that dis-
395
turbed environments outside the family such as peer
groups may contribute to deviant behavior. Our results
do not offer strong support for a genetic role in the
development of CD symptoms. However, we are not
necessarily in conflict with the above reports since fam-
ily studies cannot differentiate between whether famil-
iar effects are due to genes alone, environmental ef-
fects, or a combination of both.
Lyons and colleagues’ previous examination [Lyons
et al., 1995] of VET Registry twins’ summary scores of
juvenile antisocial traits produced consistent but not
identical results when compared with the present
analyses. This previous study analyzed data from 3,226
pairs (versus 3,336 pairs in the present study) and uti-
lized bivariate model fitting to assess the amount of
overlap in the genetic and environmental contributions
to juvenile and adult antisocial summary scores
whereas the present study utilized a dichotomous defi-
nition of CD. Lyons et al. found juvenile antisocial
traits are largely explained by environmental factors
with a small (7%) additive genetic contribution to ju-
venile antisocial traits. The present model fitting re-
sults suggest that genetic influences are not included
in the most parsimonious explanation for a report of
three or more lifetime CD symptoms. In contrast, Slut-
ske et al. [1997] showed that there was a 71% genetic
contribution to CD in male members of the Australian
Twin Registry. They also used a broad definition of
lifetime CD (three symptoms) and found no family en-
vironmental factor. There are some potential explana-
tions for this discrepancy. First, the current veteran
sample may have produced a less deviant cohort be-
cause of the elimination of subjects with severe conduct
problems through initial screening for military service.
Thus, the CD phenotype in the present study may rep-
resent more benign behavior problems that are argu-
ably more malleable and susceptible to environmental
influences than are severe antisocial behaviors. For in-
stance, Slutske et al. notes that Lyons and colleagues’
study of VET Registry twins did find stronger genetic
influences (39% variance due to genes) for “more se-
vere” antisocial symptoms such as being arrested. An
alternative explanation for differences between the
heritability of CD in the VET Registry and Australian
Twin Registry may be cultural. Future research should
investigate whether antisocial behavior is transmitted
by the same mechanisms across cultures. Additional
data collection efforts in existing twin registries may be
warranted to address this question.
The present analyses adds to the previous assess-
ment of the genetic contribution to marijuana abuse
among VET Registry twins [Tsuang et al., 1996]. Al-
though the two analyses differ in sample size and phe-
notype, the findings are consistent. The prior estimates
of 33% and 29% fall within the 95% CIs reported in the
present article for the genetic and family environmen-
tal contributions to MJ symptoms. Another recent
analysis of the subjective effects of marijuana use in
VET Registry twins found that genes account for about
one-quarter of the variation in the subjective responses
to marijuana smoking [Lyons et al., 1997]. Evidence for
genetic contributions to MJ is also supported by animal
studies. The finding that two genetically distinct
396 True et al.
strains of rat have different physiological responses to
9
-THC (the psychoactive component of marijuana) sup-
ports the conclusion that genetic factors influence re-
sponses to marijuana [Chen et al., 1991].
Our finding of a genetic contribution to three or more
lifetime symptoms of AD is consistent with well-
established results in both human and animal studies
of the genetics of alcoholism [Crabbe et al., 1994;
Heath, 1995]. The present variance component esti-
mates for alcoholism are well within the range reported
in other twin studies [Heath, 1995] including previous
findings in the VET Registry [True et al., 1996].
The present work identified a common genetic and
environmental influence on co-morbid AD symptoms
and MJ symptoms. Our findings suggest the liability
for MJ symptoms is partially due to a small amount of
variance due to genes (7.6%) and unique environmen-
tal experiences (5.4%) that overlap with AD symptoms,
and a substantial (21.3%) family environmental influ-
ence that is common to the lifetime risk of CD and AD
symptoms. A common liability for AD symptoms and
MJ symptoms corroborates the well-documented sub-
stance use patterns that show marijuana use is typi-
cally preceded by alcohol [Kandel et al., 1992]. Our re-
sults suggest this observation is partially due to vul-
nerability factors common to problem drinking and
problem marijuana use.
To test whether our results would hold when exclud-
ing abstainers, thereby excluding initiation and allow-
ing only for the risk of dependence, we fit a multivari-
ate model to CD, AD, and MJ without subjects who
were lifetime abstainers from both alcohol and mari-
juana. The best fitting model (␹221 ⳱ 20.31, p ⳱ 0.502,
AIC ⳱ −21.69) for CD, AD, and MJ without abstainers
was nearly identical to the model that included ab-
stainers, differing only in that it allowed for a signifi-
cant unique environmental path to all three pheno-
types. This suggests that the family environmental in-
fluence is significant for both an etiological model for
risk of CD symptoms among substance users and in a
model of the risk of CD symptoms, initiation of sub-
stance use, and problem use.
The shared environmental contribution to all three
phenotypes appears to be quite robust in that subse-
quent analyses with varying thresholds of substance
use produced the same result. The best fitting multiple
threshold model that allowed for the risk of developing
CD with one to two symptoms, three to four symptoms,
or greater than five symptoms of AD and MJ differed
from the single threshold model reported in the results
only in that it allowed for a common unique environ-
mental path to CD, AD, and MJ (␹221 ⳱ 31.23, p ⳱
0.07, AIC ⳱ −10.77).
A potential weakness of this work may be response
bias. Responders were those who responded to a 1987
survey and to the 1992 telephone interview used for
this study, while nonresponders answered the 1987
survey but not the 1992 interview. Of those with
greater than a high school education, 73.5% responded;
67.1% of those without college responded. More re-
sponders were employed full-time in 1992. Of those
employed full-time 72.7% responded, whereas only
55.4% of part-time or unemployed responded. The
percentage of responders was nearly equal among
those who served in Southeast Asia and those who
served elsewhere (72.4% verses 70.2%, respectively).
Another potential limitation of the present work is
the definition of three or more lifetime symptoms of AD
yielding a high (38.3%) lifetime prevalence rate in this
cohort. This may be explained by relatively easy and
inexpensive access to alcohol when respondents were
in the military. The broad definition of DSM-III-R al-
cohol dependence was captured by the algorithm ap-
plied to data collected from administration of the
DIS3R. However, after estimating the genetic contri-
bution to the narrow definition of DSM-IV alcohol de-
pendence (approximated from our data), we found a
lower prevalence rate of 26.9% DSM-IV alcoholism.
But we did not find significantly different genetic con-
tributions to alcoholism whether defined by three or
more DSM-III-R lifetime symptoms (45% due to genes)
or by the narrow criteria of DSM-IV (49% due to genes).
This suggests our model fitting results should not be
affected by the high prevalence observed for the report
of three or more symptoms of DSM-III-R alcohol depen-
dence.
In summary, we have identified a genetic component
common to lifetime AD symptoms and MJ symptoms
and a family environmental influence common to risk
of lifetime CD symptoms, AD symptoms, and MJ symp-
toms. Our analyses support the hypothesis that reduc-
ing exposure to environmental factors that contribute
to the development of CD symptoms may simulta-
neously reduce exposure to environmental factors that
influence the development of AD symptoms and MJ
symptoms among individuals at increased risk because
of familial vulnerability. These results are consistent
with family-based therapies for CD and substance de-
pendence [Diamond et al., 1996] and those that also
integrate intervention in the school, peer, and commu-
nity environment [Miller and Prinz, 1990]. Enriching
the environmental factors that could be common to CD
and substance use, such as family, school, peer, and
community experiences, may reduce the risk of both
disorders.
ACKNOWLEDGMENTS
The authors acknowledge the work of the following
people: (1) Midwest Center for Health Services and
Policy Research: Vietnam Era Twin Registry, director,
W.G. Henderson, Ph.D.; epidemiologist, J. Goldberg,
Ph.D.; registry programmer, K. Bukowski; coordinator,
M.E. Vitek; (2) VET Registry Advisory Committee:
A.G. Bearn, M.D. (past); G. Chase, Sc.D. (past); T. Col-
ton, Sc.D.; W.E. Nance, M.D., Ph.D.; R.S. Paffenbarger
Jr., M.D., Dr.P.H.; M.M. Weissman, Ph.D.; and R.R.
Williams, M.D.; (3) DVA Chief Research & Develop-
ment Officer: John R. Feussner, M.D.; DVA Health
Services Research & Development Service: deputy di-
rector, S. Meehan, M.B.A., Ph.D.; program manager, C.
Welch, III, Ph.D. The following organizations provided
invaluable support in the conduct of this study: Depart-
ment of Defense; National Personnel Records Center,
National Archives and Records Administration; the In-
ternal Revenue Service; National Opinion Research
 Genetic Influences on Conduct Disorder, Marijuana and Alcohol Dependence
Center; National Research Council, National Academy
of Sciences; the Institute for Survey Research, Temple
University. Most importantly, the authors gratefully
acknowledge the continued cooperation and participa-
tion of the members of the Vietnam Era Twin Registry.
Without their contribution this research would not
have been possible.
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