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AM. J.

DRUG ALCOHOL ABUSE, 28(3), 557–584 (2002)



Glenn D. Walters*

Psychology Services, Federal Correctional

Institution-Schuylkill, P.O. Box 700, Minersville,
PA 17954-0700


A meta-analysis was performed on 50 family, twin, and adoption

studies in which problem drinking and alcohol dependence served
as the primary criterion measure. The results showed that far from
being an established “fact,” the genetic foundations of alcohol
misuse are modest and heterogeneous. A weighted mean f effect
size of 0.12 (95% Confidence Interval ¼ 0.11 –0.12) was obtained
for the total sample of 72 effect sizes. Four potential moderator
variables (proband gender, sample nationality, pattern severity,
year of publication) were examined with outcomes confirming
that the heritability of alcohol misuse is stronger in males and in
studies employing more severe definitions of abuse (alcoholism,
alcohol dependence). When the effect size measure was restricted
to studies using male subjects with more severe diagnoses of
alcohol misuse, the unweighted mean f effect size was only 0.18
(95% Confidence Interval ¼ 0.15 –0.21), with an even smaller



Copyright q 2002 by Marcel Dekker, Inc.


weighted mean f effect size of 0.15 (95% Confidence Interval ¼

0.12 – 0.18); results which indicate an upper limit of 30 –36% for
the heritability of alcohol misuse.

Key Words: Alcohol; Alcoholism; Genetics; Heredity; Meta-


In June 1990 the Journal of the American Medical Association (JAMA)

published a paper by a group of researchers from the University of Texas
Health Science Center in San Antonio claiming that a genetic locus for alco-
holism on the Taq1 A1 allele of the dopamine D2 receptor (DRD2) gene had
been identified.[1] The news made headlines in several newspapers, was written
up in at least one national magazine, and was broadcast to millions over the
evening news. The normally reserved New York Times called it a major break-
through in the fight against alcoholism.[2] However, when JAMA published
another paper 8 months later refuting Blum et al.’s original findings[3] the news
met with none of the fanfare that had greeted the original Blum investigation. If
the Bolos study was mentioned at all it, was relegated to the back pages of
a handful of newspapers and trade magazines. Hence, much of the general
public still believes that a gene for alcoholism exists,[4] even though the bulk of
recently published studies on the DRD2 gene shed serious doubt on its status as
a marker for alcohol misuse.[5 – 9]
It is understandable that people would want to believe news that a gene
responsible for a pattern that causes serious physical, social, and economic
problems in three out of ten American families[10] had been discovered. After all,
knowledge promotes control which, in turn, reduces fear and instills hope.
However, if the knowledge is false or inaccurate then disappointment, frustra-
tion, and mistrust will surely ensue. The human genome is comprised of nearly
100,000 genes, 20,000 – 30,000 of which involve brain function.[11] That any one
of these genes accounts for more than a modicum of variance in a behavioral
pattern as intricate and multifaceted as alcohol misuse seems highly unlikely. The
DRD2 gene may well contribute to alcohol misuse but only as part of a much
larger polygenetic pattern. Schork and Schork[12] note that multiple genes can
influence complex patterns like alcohol abuse and dependence in one of five
ways: (1) general additive effect (the presence of several genes from a larger gene
pool); (2) threshold effect (the proper number of genes); (3) epistasis or gene
interaction (the proper combination of genes); (4) locus heterogeneity (more than
one gene can activate the pattern); and (5) any combination of the four previously
mentioned possibilities. The complexity of both genetics and alcohol abuse
makes it that much more difficult to believe that any one gene is responsible for a
major portion of the variance in alcohol misuse.

Before accepting the view that alcohol misuse is genetically transmitted

and that heritability for alcohol abuse is upwards of 40– 60%,[13] we must first
consider the growing body of behavior genetic research on this issue. Behavior
geneticists seek to identify the relative inheritance of complex patterns like
alcohol misuse with the aid of three primary methodologies: family studies, twin
studies, and adoption studies. The rationale behind family studies is that if a trait
or pattern is genetic then it should be more routinely observed in people with a
family history of problem drinking. In other words, the trait or pattern should run
in families. Outcomes obtained in early family studies on alcohol abuse and
dependence revealed that people with a family history of alcohol misuse were
three to four times more likely to personally misuse alcohol than persons without
a family history of alcohol misuse.[14] In so much as most families share expe-
riences as well as genes, the family method confounds biology (genetic inheri-
tance) and environment (learning). This has led to the development of twin
and adoption methodologies in behavior genetic research.
The twin method is grounded in the fact that identical or monozygotic
(MZ) twins are genetically identical, whereas fraternal or dizygotic (DZ) twins
share half their genes in common. A genetic influence is therefore implied, at least
in theory, when MZ twins display greater similarity or concordance for a trait,
behavior, or pattern than DZ twins. However, twin research rests on a tenuous
foundation of controversial assumptions. The first assumption made by supporters
of the twin method is that parental mating is random or nonassortative. Studies
addressing this issue in alcohol abusing populations have met with conflicting
results, with some studies identifying moderate levels of assortative mating in the
parents of alcohol abusers[15] and other studies showing no evidence of assortative
mating in the mothers and fathers of alcohol abusers.[16] The equal environments
assumption, a second supposition advanced by proponents of the twin method,
maintains that MZ twins are raised in environments that are no more similar than
the environments in which DZ twins are raised. Despite assertions by twin
researchers that the equal environments assumption holds up under empirical
scrutiny,[17] there is evidence that MZ twins develop significantly closer
relationships[18] and have more contact with one another than DZ twins and that
such closeness is associated with increased similarity in drinking patterns.[19]
The adoption method compares individuals adopted in early childhood
with their biological and adoptive parents on patterns like alcohol misuse.
Although the adoption method is considered superior to the family and twin
methods, it, like the other two methods, is not without limitations. Problems with
the adoption method include failure to account for time spent with the biological
mother prior to adoption, prenatal influences, and selective placement;[20] more
specific concerns have been raised about the three major adoption cohorts in
which alcohol abuse patterns have been studied. The Goodwin et al.[21,22] Danish
adoption studies, for instance, have been criticized for employing confusing and

arbitrary classification criteria and a sample comprised largely of young adults

who had not yet passed through the age of greatest risk for alcohol misuse.[23] The
Swedish adoption studies,[24,25] on the other hand, have been reproached for
relying on temperance board data because these data may confound alcohol and
criminality.[26] Finally, research on Iowan adoptees[27,28] has been criticized for
basing diagnoses of biological parent alcohol misuse on second-hand and
potentially unreliable information.[29]
There are several variables that potentially moderate the relationship bet-
ween heredity and alcohol misuse. One such variable is gender. It has long been
speculated that addictive liability for alcohol is higher in males than females. As
Hill and Smith[30] point out, however, this does not rule out a genetic effect for
female alcohol abuse and dependence. A second potential moderator of the gene –
alcohol misuse relationship is the degree to which the subject sample derives from
an ethnically homogeneous (Scandinavian countries) vs. ethnically heterogeneous
(United States) population since more homogeneous samples have lower within
group variance and a higher probability of achieving statistical significance than
more heterogeneous samples.[20] The severity of alcohol abuse is a third potential
moderating variable, for some researchers have found that heredity is more
intimately involved in alcohol dependence than alcohol abuse or problem
drinking.[31] The year a study was published is a fourth potential moderator
variable, in part because it correlates significantly with design quality.[32] To
reflect advances taking place in behavior genetic research on alcohol abuse/
dependence in the mid-1980s (e.g., routine use of blood tests for zygosity;
development of criterion definitions and methods that were more structured and
reliable than earlier definitions and methods), 1985 served as the cutting point
for a study’s year of publication.
Data for the present meta-analysis were gathered from behavior genetic
(family, twin, adoption) studies on problem drinking and alcohol dependence
in humans. Accordingly, molecular analyses, animal research, studies on
substances other than alcohol, and investigations into alcohol use rather than
misuse were excluded from this meta-analysis. In addition to explaining the
overall gene – alcohol misuse relationship and its breakdown by moderator
variable—gender (male, female), nationality (United States, foreign), pattern
severity (more severe, less severe), and year of publication (before 1985, since
1985)—the present meta-analysis also produced effect sizes for family, twin,
and adoption studies. The null hypothesis held that there would be no rela-
tionship between heredity, as measured by the three behavior genetic methodo-
logies, and alcohol abuse/dependence. In the event the null hypothesis could be
rejected it was reasoned that the gene – alcohol misuse relationship would be
stronger for males, studies conducted outside the United States, samples dis-
playing more severe patterns of alcohol misuse, and investigations published
prior to 1985.


Selection of studies for this meta-analysis began with a computerized

search of the PsycINFO and MEDLINE databases for studies published between
1970 and 2000 in which the following key words served as identifiers: alcohol,
alcoholism, drinking, gene, heredity, family history, pedigree, twin, and adoption.
Additional studies were gleaned from the reference sections of articles identified
by the electronic search. This procedure yielded 50 behavior genetic studies on
alcohol abuse/dependence (22 family studies, 18 twin studies, 10 adoption
studies) and 72 total effect sizes. Several studies employed over-lapping samples
and some investigators reported multiple outcomes for the same group of
individuals. Multiple outcomes are listed only in studies where they provide novel
information (e.g., separate diagnoses of alcohol abuse and dependence) and then
only as an averaged composite before being combined with other studies.[21,33]
A case-to-case statistical model in the form of a 2 £ 2 table of outcomes,
whereby a phi coefficient was calculated by contrasting abuse status (absent vs.
present) with genetic status (FH þ /MZ/biological parent þ vs. FH 2 /DZ/bio-
logical parent – ), was employed in this meta-analysis of behavior genetic research
on alcohol misuse. The case-to-case model was preferred over the case-to-base rate
model proposed by Gottesman and Carey,[34] in which a tetrachoric coefficient is
calculated, because the case-to-case model allows for direct comparisons of
subjects from the same sample, whether that entails contrasting people with and
without a family history of alcohol abuse/dependence, MZ and DZ twins
concordant and discordant for alcohol abuse/dependence, or adoptees with and
without a history of biological parent alcohol abuse/dependence. It was reasoned
that the case-to-case model more clearly captures the spirit of gene –alcohol
misuse research. Accordingly, only family studies possessing a control or non-
alcohol misusing comparison group are included in this meta-analysis.
The phi coefficients obtained in this study were transformed into Fisher’s z
for the purpose pooling the results of different studies and then backtransformed
into phi coefficients. The minimum, maximum, median, weighted (by sample size)
mean, and unweighted mean effect sizes (f ) were calculated, along with the 95%
confidence interval for the weighted mean effect size. The statistical procedures
used to combine studies, test for homogeneity, and compute a 95% confidence
interval were based on the work of Hedges and Olkin.[35] Sampling error was
calculated using the Schmidt – Hunter method —s2e ¼ ð1 2 r 2 Þ 2* kÞ=N—where
r 2 represents the average weighted mean of the effect size, k the number of
studies, and N the total sample size.[36] Fleiss[37] recommends use of the odds
ratio instead of the phi coefficient to summarize categorical effect size data. This
issue is taken up further in the “Discussion” section of this paper.
Additional analyses were calculated using the four moderator variables
of proband gender (male, female), sample nationality (United States, foreign),

pattern severity (more severe, less severe), and year of publication (before 1985,
since 1985). The breakdowns for gender, nationality, and year of publication are
self-evident, while pattern severity was coded less when the alcohol use pattern
was described as abuse or problem drinking and more when the pattern was
diagnosed as alcoholism or alcohol dependence. Samples were considered mixed
if they contained subjects classified as both high and low severity. Gender was
dummy coded using a three-category system (male ¼ 1, both ¼ 2, female ¼ 3),
nationality using a two-category system (United States ¼ 1, foreign or non-
United States ¼ 2), pattern severity using a three-category system (less severe ¼ 1
mixed ¼ 2, more severe ¼ 3), and year of publication using a two-category system
(before 1985 ¼ 1; since 1985 ¼ 2).


The 50 studies included in this meta-analysis of behavior genetic research

on alcohol misuse are listed in Table 1 (family studies), Table 2 (twin studies),
and Table 3 (adoption studies). Mean phi values of 0.12 (weighted) and 0.15
(unweighted) were found for the entire population of effect sizes ðk ¼ 72; total
N ¼ 58; 887Þ: These values, along with the coefficients attained by family, twin,
and adoption studies, are listed in Table 4. It should be noted, however, that
heterogeneity was high for three groups of pooled effect sizes—all studies,
Q ð71Þ ¼ 253:51; p , 0:001; family studies, Q ð30Þ ¼ 175:27; p , 0:001; and
adoption studies, Q ð10Þ ¼ 38:49; p , 0:001—and low for twin studies—
Q ð29Þ ¼ 40:07; p ¼ 0:08: Consequently, the analyses were broken down further
by moderator variable—i.e., gender (male – female), location (US-foreign),
pattern severity (more –less), and publication date (before 1985, since 1985)—
but with only a few exceptions (i.e., US-adoption studies), the heterogeneity of
the effect size estimates for the overall estimate as well as for family and adop-
tion studies remained high.
A multiple regression analysis of the four moderator variables on outcome
(phi coefficients for all effect sizes included in the overall estimate) produced a
multiple correlation of 0.38 and R 2 of 0.14. Beta weights for the four moderator
variables that were regressed onto outcome were as follows: gender (2 0.25),
nationality (2 0.14), severity (0.24), and year of publication (0.15). Only the
gender and severity betas achieved statistical significance ðp , 0:05Þ: A statistical
breakdown of effect sizes for all studies, family studies, twin studies, and
adoption studies subdivided by moderator variable can be found in Table 5.
In an attempt to identify the upper limit of heritability for alcohol misuse
the 13 (11 twin, 2 adoption) studies with moderating conditions most favorable to
a genetic interpretation of problem drinking (namely, male samples with more
severe diagnoses of alcohol misuse) were analyzed as a group. The outcome
Table 1. Family Studies on Alcohol Misuse
Family Members
Proband Subjects Control Subjects Outcome (%)a Moderating Variablesb
Location N Sex Description N Sex Description Relation Criteria Proband Control f Sex Nat Sev YP Source

Sweden 203 M Inpt and 85 M Surgical pts Father Alcohol abuse 26.2 3.4 0.26 M For More Pre [55]
outpt w/social
alcoholics consequences
United 50 M Inpt 300 M Swiss Father Alcoholism 22.0 9.7 0.14 B US More Pre [56]
States and alcoholics and surgical
F from US F and psych
United 183 M Alcoholics 441 M Mod. Father Alcoholism 4.9 0.0 0.13 M US More Pre [57]
States and drinkers
F and non-

24 F Alcoholics 662 F Mod. drinkers Father Alcoholism 4.2 1.2 0.05 F US More Pre
and non-
United 500 M Inpt 230 M Hospital Parents Alcoholism 27.6 0.9 0.32 B US More Pre [58]
States and alcoholics and employee
F F controls
Canada 56 M Inpt 944 M Inpt with non- Father Excessive 23.2 10.0 0.10 B For More Pre [59]
and alcoholics and alcohol alcohol
F F abuse dx consumption
United 62 M Inpt 608 M Pts w/medical Father Hospitalization; 16.1 6.2 0.11 B US More Pre [60]
States and alcoholics and or affective neg. cons-
F F disorder dx equences from

(continued )

Table 1. Continued

Family Members
Proband Subjects Control Subjects Outcome (%)a Moderating Variablesb
Location N Sex Description N Sex Description Relation Criteria Proband Control f Sex Nat Sev YP Source

United 40 M Alcoholics 40 M
Pts with Father Alcohol addiction; 2.5 2.5 0.00 M For More Pre [61]
Kingdom physical hospitalization;
illness withdrawal
unrelated symptoms
to alcohol
United 56 F Inpt 56 F Nonalcoholic Father Heavy 46.4 12.5 0.37 F US More Pre [62]
States alcoholics drug drinking
United 32 M Alcoholic 132 M Nonalcoholic Parents Alcoholism 62.0 20.0 0.38 B US More Pre [63]
States and half- and half-
F siblings F siblings
United 51 M Inpt 7 M Inpt psych 1st Alcoholic 56.8 28.6 0.18 M US More Pre [15]
States alcoholics controls degree drinking style
32 F Inpt 32 F Inpt psych 1st Alcoholic 59.4 50.0 0.09 F US More Pre
alcoholics controls degree drinking style
United 39 M Dependent 723 M Nonalcohol Parents Alcoholism/problem 30.8 10.6 0.14 M US More Post [64]
States prob and abusers drinking
drinking F
21 F Dependent 989 F Nonalcohol Parents Alcoholism/problem 23.8 17.9 0.02 F US More Post
prob abusers drinking
United 72 M Alcohol 1277 M Nonalcohol 1st and Alcoholism 40.3 22.5 0.09 B US Less Post [65]
States and abusing and abusing 2nd
F adol F adol degree
United 166 M DSM-III 455 M Nonalcohol Parents Alcohol abuse 36.1 20.4 0.16 M US Mix Post [66]
States alcohol abusers or dependence
67 F DSM-III 971 F Nonalcohol Parents Alcohol abuse 50.7 24.0 0.15 F US Mix Post
alcohol abusers or dependence
United 60 M DSM-III 159 M Nonalcohol Parents Alcoholism 65.0 57.9 0.06 B US Mix Post [48]
States and alcohol and abusers
F abuse/dep F
United 89 M Outpt 83 M Nonproblem 1st and Problem 55.1 16.9 0.40 B For Less Post [67]
Kingdom and problem and drinkers 2nd drinking
F drinkers F degree
United 338 M DSM-III 2135 M Nonalcohol 1st Alcoholism 31.6 17.0 0.13 B US Mix Post [68]
States and alcohol and abusers degree
F abuse/dep F
United 2806 M DSM-III-R 20,346 M Nonalcohol 1st Alcoholism or 32.9 21.8 0.09 B US More Post [69]
States and alcohol and abusers degree problem drinking
F dep F
Denmark 49 M DSM-III-R 182 M Nonalcohol Parents Treatment for 73.5 62.7 0.10 M For Less Post [70]
alcohol abusers alcoholism

39 M DSM-III-R 182 M Nonalcohol Parents Treatment of 76.9 62.7 0.12 M For More Post
alcohol abusers alcoholism
Germany 66 M Inpatients 64 M Inpatients 1st Alcoholism 81.2 32.8 0.50 M For More Post [43]
w/alcohol- w/depres- degree
ism dx sion dx
38 F Inpatients 96 F Inpatients 1st Alcoholism 42.1 24.0 0.18 F For More Post
w/alcohol- w/depres- degree
ism dx sion dx
United 38 M DSM-III-R 247 M Nonalcohol 1st and Father þ another 71.0 44.5 0.18 M US Less Post [71]
States alcohol abusers 2nd 1st or 2nd degree
abuse degree alcohol

(continued )

Table 1. Continued

Family Members
Proband Subjects Control Subjects Outcome (%)a Moderating Variablesb
Location N Sex Description N Sex Description Relation Criteria Proband Control f Sex Nat Sev YP Source

73 M DSM-III-R 247 M Nonalcohol 1st and Father þ another 75.3 44.5 0.26 M US More Post
alcohol abusers 2nd 1st or 2nd
dep degree degree alcohol
United 916 M DSM-III-R 111 M Nonalcohol 1st Alcohol 49.7 19.8 0.17 M US More Post [72]
States alcohol abusers degree dependence
296 F DSM-III R 106 F Nonalcohol 1st Alcohol 23.8 6.0 0.12 F US More Post
alcohol abusers degree dependence
United 640 M DSM-III-R 343 M Nonalcohol 1st Alcohol abuse 45.6 19.8 0.26 M US More Post [53]
States alcohol abusers degree or dependence
166 F DSM-III-R 245 F Nonalcohol 1st Alcohol abuse 52.4 20.4 0.33 F US More Post
alcohol abusers degree or dependence

Note: adol ¼ adolescent; dep ¼ dependence; dis ¼ disorder; dx ¼ diagnosis; inpt ¼ inpatient; neg ¼ negative; outpt ¼ outpatient; prob ¼ problem; psych ¼
psychiatric; pts ¼ patients.
Outcome is the percentage of proband (alcohol abusing) and control (nonalcohol abusing) subjects with a family history of alcohol abuse, family being defined under
relation and alcohol abuse being defined under diagnostic criteria.
Moderating variables: proband sex or gender (M ¼ male, F ¼ female, B ¼ both); proband nationality (US ¼ United States, For ¼ foreign or outside the United
States), Sev ¼ severity of alcohol abuse in proband subjects (More ¼ more severe, Less ¼ less severe, Mix ¼ mixture of high and low severity), YP ¼ year of
publication (Pre ¼ before 1985, Post ¼ since 1985).
Table 2. Twin Studies on Alcohol Misuse
MZ Twins DZ Twins Moderating Variablesa

Location Diagnostic Criteria Nb Sex Concordc Nb Sex Concordc f Sex Nat Sev YP Source

Sweden Alcohol Abuse 58 M 54.0 138 M 28.0 0.24 M For Less Pre [73]
Chronic Alcoholism 27 M 71.0 60 M 32.0 0.36 M For More Pre
Finland Alcoholism 172 M 26.0 557 M 12.0 0.15 M For More Pre [74]
Heavy Alcohol Use 198 M 75.0 641 M 63.0 0.02 M For Less Pre
Sweden Alcoholism (750)d M and F 22.0 M and F 16.0 0.08 B For More Pre [75]
United Alcoholism 15 M 33.0 20 M 30.0 0.04 M For More Pre [76]
13 F 8.0 8 F 13.0 2 0.08 F For More Pre
United Alcoholism 271 M 26.3 444 M 11.9 0.18 M US More Pre [77]

Finish Twin Cohort


Finland Alcoholism 69 M 13.0 175 M 5.7 0.12 M For More Pre [78]
7 F 0.0 20 F 0.0 0.00 F For More Pre
Finland Broad definition of 64 M 10.9 186 M 6.4 0.07 M For Less Post [79]
alcohol abuse
Swedish Twin Registry I
Sweden Alcoholism 95 M 12.6 187 M 9.1 0.07 M For More Post [80]

Minnesota Twin Registry

United DSM-III Alcohol 50 M 74.0 64 M 57.8 0.17 M US Less Post [44]
States Abuse
DSM-III Alcohol 39 M 59.0 47 M 36.2 0.23 M US More Post
DSM-III Alcohol 30 F 26.7 22 F 27.3 2 0.01 F US Less Post
DSM-III Alcohol 24 F 25.0 20 F 5.0 0.27 F US More Post

(continued )

Table 2. Continued

MZ Twins DZ Twins Moderating Variablesa

Location Diagnostic Criteria Nb Sex Concordc Nb Sex Concordc f Sex Nat Sev YP Source

United Cloninger Type I 54 M 48.1 65 M 32.3 0.16 M US Less Post [33]

Cloninger Type II 54 M 57.4 65 M 32.3 0.25 M US More Post

Virginia Twin Registry

United Alcohol Dependence 203 F 26.2 154 F 11.9 0.17 F US More Post [16]
Problem Drinking 73 F 46.9 55 F 31.5 0.16 F US Less Post
United DSM-IV Alcohol 505 M 40.0 316 M 29.8 0.11 M US Less Post [81]
States Abuse
DSM-IV Alcohol 378 M 31.7 436 M 19.3 0.14 M US More Post
Volunteer Twin Sample
United Problem Drinking 42 M 28.6 12 M 8.3 0.20 M US Less Post [45]
Problem Drinking 63 F 11.1 24 F 8.3 0.04 F US Less Post

Australian Twin Registry

Australia Alcohol Dependence 396 M 38.9 231 M 19.9 0.20 M For More Post [41]
Alcohol Dependence 932 F 20.9 534 F 9.2 0.11 F For More Post
Swedish Twin Registry II
Sweden Temperance Board 753 M 31.3 1209 M 21.6 0.11 M For Less Post [82]
World War II Twin Registry
United Heavy alcohol 709 M 28.6 842 M 21.1 0.09 M US Less Post [83]
States Consumption

Vietnam Era Twin Registry

United Alcoholism 710 M 53.2 588 M 43.2 0.10 M US More Post [84]
Canadian Twin Registry
Canada Alcohol Misuse 131 M 74.0 76 M 52.6 0.22 M For Less Post [54]
215 F 67.0 175 F 60.0 0.07 F For Less Post

Moderating variables: proband sex or gender (M ¼ male, F ¼ female, B ¼ both); proband nationality (US ¼ United States, For ¼ foreign or outside the United
States), Sev ¼ severity of alcohol abuse in proband subjects (More ¼ more severe, Less ¼ less severe, Mix ¼ mixture of high and low severity), YP ¼ year of
publication (Pre ¼ before 1985, Post ¼ since 1985).

Number of twin pairs.
Pair-wise concordance for alcohol abuse.
The authors of this study failed to specify the number of MZ and DZ twins completing questionnaires on alcohol use and abuse patterns but did indicate that
approximately 1500 pairs of twins were sent questionnaires. Given a 50% rate of return of mailed questionnaires it is estimated that approximately 750 twin pairs
participated in this study. The phi was calculated from the percentages given by the authors and an N of 750 was used to pool these data with other twin and genetic
studies in the derivation of a weighted mean f.
SR ¼ self report.

Table 3. Adoption Studies on Alcohol Misuse

Proband Subjects Control Subjects Moderating Variablesa

Location Diagnostic Criteria N Sex Outcomeb N Sex Outcomeb f Sex Nat Sev YP Source

United States Alcohol abuse 27 M and F 3.7 22 M and F 4.5 2 0.02 B US Less Pre [85]
Danish Adoption Cohort
Denmark Alcoholism 55 M 18.2 78 M 5.1 0.21 M For More Pre [21]
Problem drinking 55 M 9.1 78 M 14.1 2 0.08 M For Less Pre
Denmark Alcoholism 6 F 33.3 90 F 52.2 2 0.09 F For More Pre [22]
Stockholm Adoption Study
Sweden Alcohol abuse 89 M 39.4 892 M 13.1 0.21 M For Less Pre [86]
Sweden Alcohol abuse 172 F 7.0 741 F 2.6 0.10 F For Less Pre [24]
Sweden Severe alcohol abuse 307 M 7.8 555 M 4.9 0.06 M For Less Pre [87]
Sweden Alcohol abuse 108 M 24.1 469 M 12.8 0.12 M For Less Post [25]
114 F 0.9 546 F 1.3 2 0.01 F For Less Post
Iowa Adoption Cohort
United States Alcoholism 23 M 13.0 69 M 1.4 0.26 M US More Pre [27]
United States Alcohol abuse 39 M and F 48.7 404 M and F 13.9 0.25 B US Less Post [28]
United States Alcohol abuse 49 M and F 70.6 34 M and F 55.1 0.16 B US Less Post [88]

Moderating variables: proband sex or gender (M ¼ male, F ¼ female, B ¼ both); proband nationality (US ¼ United States, For ¼ foreign or outside the United
States), Sev ¼ severity of alcohol abuse in proband subjects (More ¼ more severe, Less ¼ less severe, Mix ¼ mixture of high and low severity), YP ¼ year of
publication (Pre ¼ before 1985, Post ¼ since 1985).
Percent of proband (alcohol abusing) and control (nonalcohol abusing) adoptees with at least one alcohol abusing biological parent.

Table 4. Effect Sizes for Studies on Alcohol Misuse

Twin Adoption
Overall Effect Family Studies Studies Studies
Number of f estimates 72 31 30 11
Maximum f 0.50 0.50 0.36 0.26
Median f 0.13 0.14 0.12 0.11
Minimum f 2 0.09 0.00 20.08 2 0.09
Unweighted mean (f ) 0.15 0.18 0.13 0.10
Weighted mean (f ) 0.12 0.12 0.12 0.12
95% Confidence intervala 0.11 – 0.12 0.11 –0.13 0.10– 0.13 0.09 – 0.14
Calculated from the weighted mean f and standard error of the weighted mean.

of this restricted analysis revealed a weighted mean f of 0.15 (95% confidence

interval ¼ 0.12 –0.18) and unweighted mean f of 0.18 (95% confidence
interval ¼ 0.15 –0.21) in a sample of homogeneous effect sizes, Q ð12Þ ¼ 15:67;
p . 0:10: Heritability is calculated by doubling the mean effect size estimates of
a correlational measure like the phi coefficient. This results in heritability
estimates of 30% (weighted) and 36% (unweighted) for males with severe
alcohol dependence, which is somewhat higher than the 20 – 26% heritability
suggested by the full sample of twin and adoption studies.


The outcome of this meta-analysis paints a somewhat different picture than

the one drawn by the more enthusiastic proponents of the genetic view of alcohol
misuse (Cloninger in Refs. [13,38,39]). The heritability of alcohol misuse, which
can be estimated by doubling the effect sizes attained in the present meta-analysis
by all twin and adoption studies, appears to range between 20 and 26%. Even
when the analyses are restricted to studies most favorable to the genetic
hypothesis—i.e., males diagnosed with severe forms of alcohol dependence—
heritability does not appear to exceed 30– 36%, which is somewhat lower than
the 40 – 60% rate normally cited in the literature. Therefore, Wilson and
Crowe’s[40] quandary over whether we should identify people at risk for alcohol
misuse for preventative purposes is deemed moot to the extent that the gene –
alcohol misuse relationship is probably too weak and variable to permit reliable
identification. Our limited time, energy, and financial resources might therefore
be better spent clarifying the boundaries and parameters of this relationship than
metaphorically spinning our wheels searching for phantom “alcoholism genes”
independent of their environmental context.

Table 5. Effects of Moderator Variables on the Genes – Alcohol Misuse Relationship

Proband Gender Nationality Pattern Severity Year of Publication

Male Female US Foreign More Less Pre-85 Post-85

Overall effect
Number of f estimates 38 20 41 31 43 27 29 43
Maximum f 0.50 0.37 0.38 0.50 0.50 0.40 0.38 0.50
Median f 0.15 0.10 0.16 0.09 0.14 0.11 0.11 0.14
Minimum f 0.00 20.09 20.02 20.09 20.09 20.08 20.09 20.01
Unweighted mean (f ) 0.16 0.10 0.16 0.13 0.17 0.12 0.13 0.16
Weighted mean (f ) 0.14 0.10 0.12 0.12 0.12 0.11 0.14 0.11
95% Confidence 0.13–0.16 0.08–0.12 0.11–0.13 0.10–0.13 0.11–0.13 0.09–0.13 0.12–0.15 0.10–0.12
Family Studies
Number of f estimates 13 8 23 8 23 4 12 19
Maximum f 0.50 0.37 0.38 0.50 0.50 0.40 0.38 0.50
Median f 0.17 0.14 0.14 0.15 0.14 0.14 0.14 0.15
Minimum f 0.00 0.02 0.02 0.00 0.00 0.09 0.00 0.02
Unweighted mean (f ) 0.19 0.17 0.17 0.21 0.19 0.20 0.18 0.18
Weighted mean (f ) 0.19 0.12 0.11 0.17 0.11 0.13 0.16 0.11
95% Confidence 0.16–0.21 0.09–0.15 0.10–0.12 0.13–0.21 0.10–0.12 0.09–0.18 0.13–0.19 0.10–12
Twin studies
Number of f estimates 20 9 14 16 17 13 10 20
Maximum f 0.36 0.27 0.27 0.36 0.36 0.24 0.36 0.27
Median f 0.14 0.07 0.16 0.11 0.14 0.11 0.10 0.14
Minimum f 0.02 20.08 20.01 20.08 20.08 20.01 20.08 20.01
Unweighted mean (f ) 0.15 0.08 0.15 0.11 0.14 0.12 0.11 0.14
Weighted mean (f ) 0.12 0.11 0.12 0.11 0.13 0.10 0.12 0.12
95% Confidence 0.10–0.14 0.07–0.18 0.10–0.15 0.09–0.13 0.11–0.16 0.08–0.12 0.08–0.15 0.10–0.14
Adoption studies
Number of f estimates 5 3 4 7 3 9 7 4
Maximum f 0.26 0.10 0.26 0.21 0.26 0.25 0.26 0.25
Median f 0.12 20.01 0.20 0.06 0.21 0.10 0.06 0.14
Minimum f 0.06 20.09 20.02 20.09 20.09 20.08 20.09 20.01
Unweighted mean (f ) 0.14 20.00 0.16 0.06 0.13 0.09 0.08 0.13
Weighted mean (f ) 0.14 0.04 0.22 0.10 0.14 0.11 0.12 0.11

95% Confidence 0.10 2 0.17 20.00–0.09 0.15–0.29 0.07–0.13 0.03–0.24 0.08–0.14 0.08–0.15 0.06–0.15

Calculated from the weighted mean f and standard error of the weighted mean.

Four potential moderator variables were examined in this study: proband

gender, sample nationality, pattern severity, and year of publication. Congruent
with a number of individual studies in which male and female probands have been
compared,[25,41 – 45] the heritability of alcohol misuse was stronger in males than
females. While this may reflect a genuine male – female difference in genetic
liability for alcohol misuse as represented by Cloninger’[46] Type II or male-
limited alcoholism pattern, many of the comparisons involving females suffered
from low power due to small sample sizes and decreased rates of alcohol misuse
compared to males. When analyses were restricted to female studies with sample
sizes larger than 100 ðk ¼ 13Þ the weighted effect size rose slightly (0.10 – 0.11)
and the unweighted effect size showed moderate improvement (from 0.10 to 0.14),
both figures of which approach the effect sizes attained for males in this meta-
analysis. These findings lend support to Heath’s[39] assertion that the gene – alcohol
misuse association may be as strong and consistent in women as it is in men.
There is evidence from the results of this meta-analysis that the severity of
alcohol abuse may moderate the gene – alcohol misuse relationship. One might
be tempted to conclude from this that there are two types of alcohol misuse, one
which is more severe and genetically influenced and the other which is less
severe and mediated principally by environmental factors. These two patterns
conform in a general way to Cloninger’s[46] Type II (male-limited) and Type I
(milieu-limited) categories of alcohol misuse, respectively. However, the pre-
sent findings are also compatible with a continuum view of alcohol misuse in
which the continuum extends from mild to severe alcohol misuse and where
genetic contributions vary both quantitatively and qualitatively at different
points along the continuum. In contrasting the dichotomy and continuum views
on the gene – alcohol misuse relationship we would be well advised to keep in
mind that while the difference in effect sizes for studies using more and less
severe definitions of alcohol misuse was modest to moderate, the confidence
intervals for more and less severe definitions of alcohol misuse overlap signi-
ficantly (Table 5).
The third and fourth moderating variables examined in this meta-analysis
(sample nationality, date of publication) had little appreciable effect on the results
obtained by this study. This is good news for supporters of the genetic perspective
on alcohol misuse for two reasons. Firstly, it confirms that the gene – alcohol
misuse relationship is not restricted to ethnically homogeneous populations for it
was just as likely to surface in a culturally diverse culture like the United States as
it was in more ethnically homogeneous cultures such as those found in the
Scandinavian countries. Secondly, a significant genetic effect is just as likely to
occur in more recently published and presumably, more methodologically sound
investigations as it is to appear in earlier and less methodologically rigorous
studies. This second finding certifies that the gene – alcohol misuse correlation is
not simply an artifact of poor quality research designs.

Overall, the four moderator variables accounted for only 14% of the
variance in the effect sizes procured from this meta-analysis. This indicates that
much of the heterogeneity in the gene – alcohol misuse relationship remains
unexplained. Measurement error and interactions leading to nonshared environ-
mental effects may account for a substantial portion of the heterogeneity in effect
sizes. What variance remains once measurement error and nonshared environ-
mental experience are extracted from the equation is probably attributable to
variables that have not been routinely investigated in behavior genetic research
on alcohol misuse. Either way, a great deal more research is required before we
are in a position to offer firm conclusions as to the relationship between here-
dity and alcohol misuse. If the relative modesty of the effect sizes revealed in this
meta-analysis is not enough to discourage simplistic genetic interpretations of
alcohol misuse then the heterogeneity witnessed between the different studies
should send a clear message of caution to even the most ardent of genetic
Comparing the present findings with outcomes registered in an earlier
meta-analysis of crime studies[32] reveals that the gene – alcohol misuse relation-
ship is no stronger, and is actually weaker for five of the six family, twin, and
adoption contrasts (the weighted effect size for adoption studies being the one
exception), than the gene – crime relationship (see Fig. 1). These findings insinu-
ate that crime may be as strongly genetic as alcohol abuse. Other results denote
that a portion of the variance traditionally ascribed to genetic differences in alco-
hol abuse may actually be a function of genetic differences in crime. Besides
Cloninger’s[46] observation that the fathers of Type II alcoholics own more
extensive records of prior criminality than the fathers of persons exhibiting the
less genetically influenced Type I pattern, Cadoret and Gath[47] ascertained that
childhood conduct disorder predicted later alcohol misuse in adoptees and cor-
related, albeit nonsignificantly, with biological parent alcohol misuse. Further-
more, Stabenau[48] determined that a diagnosis of antisocial personality disorder
achieved a three-fold increase in liability for alcohol abuse, doubling the con-
tributions of male gender and a family history of alcohol misuse in predicting
personal misuse of alcohol.
In interpreting the results of the present meta-analysis it should be kept
in mind that the case-to-case method upon which the current analyses were based
possesses less statistical power than the multivariate and model testing procedures
used in many of the individual studies. However, multivariate and model testing
procedures also tend to capitalize on large sample sizes, whereas the case-to-case
approach provides a more equitable and conservative estimate of the gene –
behavior relationship.[49] This may explain why the heritability estimates from
this meta-analysis were lower than anticipated and may even slightly under-
estimate the gene – alcohol misuse relationship. Nevertheless, the case-to-case
method permits inclusion of many more studies than could be accommodated

Figure 1. A Comparison of Effect Sizes for Crime and Alcohol Misuse.

by multivariate or model testing procedures. By providing a statistic common to

all three behavior genetic methodologies, the case-to-case approach furnishes a
procedure by which family, twin, and adoption studies can be combined and
compared. Despite its inclusiveness, the case-to-case method cannot encompass
every relevant study. As such, individual studies not covered in this meta-analysis
and excluded analyses from some of the studies included in the meta-analysis
should be considered alongside the present meta-analytic results as part of a
comprehensive evaluation of the proposed gene – alcohol misuse relationship.
One such study was an investigation by Vernon et al.[50] in which the social
learning concept of alcohol expectancies was found to be influenced by genetic
factors, suggesting that heredity may be involved in alcohol misuse in a number of
subtle and intricate ways.
Advocates of the twin method will probably take issue with the fact that
pair-wise rather than proband-wise concordance was used to calculate the effect

sizes for the twin study portion of this meta-analysis. However, the pair-wise
method (concordant twin pairs/concordant twins pairs þ discordant twin pairs)
seems more consistent with the way in which family and adoption study data
were analyzed in this meta-analysis than the proband-wise method (2 £
concordant twin pairs/[2 £ concordant twin pairs] þ discordant twin pairs).
Furthermore, there was very little difference in effect sizes between the pair-wise
and proband-wise estimates. Substituting the proband-wise calculations for the
pair-wise calculations increased the unweighted mean f effect size estimate
by 0.01 (from 0.13 to 0.14), the weighted mean f effect size estimate by 0.01
(from 0.12 to 0.13), and elevated the 95% confidence interval from 0.10– 0.13 to
0.12– 0.15. Odds ratios were also calculated for all proband-wise twin com-
parisons, the outcome of which yielded an unweighted mean effect size of 2.15, a
weighted mean effect size of 1.92, and a 95% confidence interval of 1.33 –2.61.
These findings imply that neither the proband-wise method of calculating twin
concordance nor the odds ratio approach advocated by Fleiss[37] significantly
alter the pattern of results obtained from phi coefficients of pair-wise twin data.
The outcomes achieved when behavior genetic research on alcohol abuse
and dependence is subjected to meta-analysis show that these patterns are
heritable to some extent, with the degree and type of influence still requiring
further clarification. At this point in time the effect of genes on alcohol misuse
cannot be denied, but neither can the effect of the environment. There has been
a discernable shift within the alcohol abuse field over the past several years which
has seen biological factors displace environmental and learning factors in
explanations of problem drinking, a shift that threatens to accelerate as genetic
mapping becomes a reality.[51,52] Whether shared environmental experience is as
pivotal to alcohol misuse as it is to crime remains to be seen, although the inter-
active nature of nonshared environmental influence apparently plays a crucial
role in the initiation and maintenance of alcohol misuse. In closing it is important
to reiterate that the intent of this paper has not been to disparage or discourage
genetic research on alcohol abuse and dependence, but rather to call for greater
balance in our views on the subject. Rapprochement between the biological and
learning camps is within our grasp but only if we are willing to reject genetic
and environmental reductionism as a means of achieving a more comprehensive
and interactive perspective on problem drinking.


The author would like to thank Scott Stoltenberg and Kerry Jang for their
assistance in providing additional data from the Curran et al. and Jang et al.[53,54]
studies, respectively. The assertions and opinions contained herein are the

private views of the author and should not be construed as official or as

reflecting the views of the Federal Bureau of Prisons or the United States
Department of Justice.


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