ELSEVIER Drug and Alcohol Dependence 42 (1996) l-10

Mating assortment and the liability to substance abuse’

M.M. Vanyuko+*, M.C. Nealeb, H.B. Moss”, R.E. Tarter” ‘Center for Education and Drug Abuse Research (CEDAR)2, Department of Psychiatry, University of Pittsburgh School of Medicine,

3811 O’Hara Street, Pittsburgh, PA 15213, USA bDepartment of Psychiatry, Medical College of Virginia/ Virginia Commonwealth University, Richmond, VA 23298, USA

Received 1 June 1995; accepted 18 April 1996

Abstract

Assortative mating can exert a profound influence on the phenotypic composition of the population since it may result in an increase in the frequency of the genotypes associated with extreme phenotypes. Applied to the risk for a disorder such as substance abuse, this would mean a possibility for an increase in the risk and severity of the disorder in consecutive generations. This paper reviews the theoretical and empirical literature on mechanisms related to mate resemblance for the liability to substance abuse, sources and consequences of such resemblance, and suggests directions for further research.

Keywords: Assortative mating; Social homogamy; Contagion; Heritability

1. Introduction

Presumed mechanisms of mate selection range from “marriages are made in heaven” to the more prosaic- limited “choice of potential partners”. While individual choice may be mainly determined by random “romantic infatuation” (Lykken and Tellegen, 1993), one of the most important mechanisms that contribute to the mar- ital structure of the population is a form of non- random mating termed assortment. Assortment can profoundly influence phenotypic distributions on the traits which are involved in mate selection. If such a trait is the liability to a disorder, assortment may be among the processes contributing to the persistence of the disorder in the population. This paper deals with mating assortment in relation to a behavioral trait whose phenotypic distribution has a great impact on societal problems-the liability to substance abuse.

* Corresponding author. E-mail: mmv@vms.cis.pitt.edu ’ Supported by the National Institute on Drug Abuse (PSO

DA05605 and R29 DA08955). ’ CEDAR is a consortium between St. Francis Medical Center and

the University of Pittsburgh.

2. Assortment as a phenomenon

Assortative mating is a non-random pairing of mates with regard to a trait or traits. Preferential mating based on the partners’ phenotypes (a phenotype is an individual value of the trait), rather than genotypes, differentiates between phenotypic assortment and an- other kind of non-random mating, inbreeding (mating between blood relatives). Whereas both assortment and inbreeding can result in a non-zero phenotypic correla- tion between mates, mate phenotypic resemblance is primary under assortment and secondary under in- breeding. Conversely, mate genotypic similarity is pri- mary under inbreeding and secondary under assortment.

Mate correlation, or homogamy, may be due to not only phenotypic assortative mating, but also to markedly different mechanisms, such as social ho- mogamy and contagion. Contagion refers to the direct influence of one partner’s behavior on the other part- ner’s behavioral phenotype. In social homogamy, corre- lations for behavioral traits between mates are caused by primary correlations in their environments that con- tribute to variation in the trait. In contrast to the effects

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2 MM. Vanyukov et al. / Drug and Alcohol Depend’ence 42 (1996) l-10

of phenotypic assortment, neither social homogamy for the trait (unless there is genotype-environment covaria- tion) nor contagion lead to changes in the genetic structure of the population, because these causes of spousal phenotypic similarity generally do not alter the frequencies of genotypes.

Theoretically, observed similarity between spouses may also arise from attrition of less similar couples due to divorce, age-related processes common for both spouses (e.g., decrease in stature with aging) (Price and Vandenberg, 1980) or secular trends (e.g., increase in stature in consecutive generations) (Cavalli-Sforza and Bodmer, 1971). Therefore, it is important to differenti- ate between these possible causes of mate similarity.

The regularities and consequences of assortative mat- ing were studied in depth by Fisher (1918) and Wright (1921) and reviewed by Crow and Felsenstein (1968). In comparison to inbreeding, phenotypic assortment re- sults in a larger increase in its variance and a lesser increase in the homozygosity of the population. The main effect of assortment on the genetic structure of the population is linkage disequilibrium between genes which contribute to the variation in the trait (“associa- tion between genes of like effect” (Crow and Felsen- stein, 1968) in gametes). This leads to an increase such that the frequency of genotypes associated with extreme phenotypes over the values expected in a randomly mating population. Assortative mating induces genetic correlations between unrelated spouses, inasmuch as their phenotypic resemblance is caused by the correla- tion between genes contributing to the trait’s pheno- typic variation. Moreover, as phenotypic assortment induces correlations between spousal environments, it also leads to augmented environmental similarity be- tween parents and children. It is important, therefore, that assortative mating increases parent-offspring phe- notypic correlations regardless of whether they are mostly genetic or mostly environmental in origin.

This is true, in particular, for liabilities to disorders. The term liability was introduced to human genetics by Falconer (1965) “to express not only the individual innate tendency to develop or contract the disease, i.e., his susceptibility in the usual sense, but also the whole combination of external circumstances that make him more or less likely to develop the disease... The point on the scale of liability above which all individuals are affected and below which are normal will be called the ‘threshold”’ (p. 52). Many liabilities to mental disor- ders, such as substance use disorders, are most likely characterized by the multifactorial mode of inheritance, when the variation in individual liability phenotypes (risk for and severity of the disorder) is contributed by both genotypic variation determined by a number of genes and the diversity of environmental conditions. This phenotypic variation in the population is described by the normal distribution, with a threshold whose

location is contingent on time- and place-related con- sensus.

For the multifactorially inherited liability to a disor- der, an extreme, suprathreshold, phenotype is the disor- der itself. Therefore, the genetic events associated with positive assortment for the liability may result in an increment in the frequency and severity of the disorder in the population. As the following discussion demon- strates, the relevance of the phenomenon of assortment to the problem of substance abuse is supported by data on the significant transmissibility (including heritability) of the liability to substance abuse and personality char- acteristics associated with that liability, and by the findings suggesting homogamy for this trait.

3. Heritability of the liabilities to substance use disorders

Heritability of a trait is the proportion of its pheno- typic variance contributed by genotypic differences be- tween individuals in a given population. In addition to the influence of the properties of the population, esti- mates of heritability can be affected by the violations of the assumptions of the model used to obtain them (e.g., differences in the environments of monozygotic and dizygotic twins, or selective placement in adoption stud- ies, or non-random mating). Heritability estimates ob- tained in one population cannot be automatically assumed to be the same in another population and cannot be used to explain phenotypic differences be- tween populations (even if heritability in each popula- tion were unity, phenotypic differences between populations could be totally environmental). It should be emphasized that heritability as well as its environ- mental complement in phenotypic variation (sometimes termed environmentality) do not have any direct rela- tion to the causes of phenotypes (e.g., etiology of a disorder). By definition, heritability and environmental- ity refer only to the causes of phenotypic variation and covariation. Clearly, if “it is important to avoid such short-hand expressions as ‘height is genetic’ when really we mean ‘individual differences in height are mainly genetic”’ (Neale and Cardon, 1992, p. 4), it is even more important when we consider behavioral/psycho- logical traits. For instance, even if heritability of the liability to substance abuse were in fact lOO%, it would neither give us information about the causes of a particular individual’s drug dependence nor tell us how to treat (or, as some might think, not to treat, because it is ‘genetic’) this person’s addiction. Preventing an individual from exposure to drugs would prevent his/ her drug use and abuse regardless of heritability. Such heritability would tell us, however, that, in the popula- tion where this estimate was obtained, variation in relevant environmental conditions is negligible com-

MM. Vanyukov et al. / Drug and Alcohol Dependence 42 (1996) l-10 3

pared to relevant genotypic variation (this situation could probably be observed, for instance, if everybody was getting the same exposure to a drug as a matter of everyday routine). For many disorders, liability to which is far from being lOOoh heritable, efficient treat- ment methods are not encountered within the range of natural environmental conditions (e.g., synthetic antibi- otics). Conversely, the treatment of a disorder, the liability to which has heritability close to lOO%, can be entirely environmental (e.g., phenylketonuria).

In practice, with current methodology, an estimate of heritability summarizes a relative role of genetic factors in the similarity within and between different classes of relatives (usually monozygotic and dizygotic twins). Because of the restrictions imposed on the models of covariation between relatives by the data available, genetic contribution to phenotypic variation is esti- mated mainly as narrow sense heritability, or additive genetic variance (which is determined by differences between homozygotes), while genetic dominance vari- ance (due to the deviation of heterozygotes from the average between homozygotes) and other genetic com- ponents of phenotypic variance are usually assumed to be unimportant. Two kinds of environmental variance components are evaluated. Shared environment is mod- eled as a source of non-genetic variation that the rela- tives participating in the study (e.g., twins) have in common and which contributes to their similarity (in- terfamilial variation in common experiences), while nonshared environment represents sources of non- genetic variation which contribute to the relatives’ dis- similarity (intrafamilial variation in unique experiences as well as measurement error or “unreliability” vari- ance (Neale and Cardon, 1992)).

Data from genetic studies suggest that interindividual differences in the liabilities to substance abuse and alcoholism are, to a large degree, determined by the variation in individual genotypes. Significant differences in concordances between monozygotic (MZ) and dizygotic (DZ) twins for a diagnosis of the presence/ab- sence of substance abuse (other than alcohol abuse and excluding tobacco abuse) have been shown for males but not females (Pickens et al., 1991). The genetic component of liability variance was estimated at 0.31 in males and 0.22 in females. Important gender differences in the composition of the liability variance were ob- served in the environmental components. Whereas al- most all phenotypic variation in females was determined by nonshared environment (0.71), shared environmental component being negligible (0.07), envi- ronmental variation in males was determined mostly by shared environment (0.51). An additive genetic model fitted best for abuse of various classes of psychoactive compounds, including stimulants (h* = 0.40), sedatives (h* = 0.56), cocaine/crack (h* = 0.38), heroin (h* = 0.62) and PCP/LSD (h* = 0.60). The exception was abuse of

marijuana where both additive genetic and common environmental effects were significant (0.39 and 0.33, respectively) (Goldberg et al., 1993).

Significant broad sense heritability (including genetic additive as well as dominance components of variance) for the liability to drug abuse (0.46) has been shown in a study of monozygotic twins reared apart (Grove et al., 1990). Importantly, a high genetic correlation (0.78) between alcohol abuse and/or dependence and drug abuse was found in this study. It has also been shown in an adoption study that alcohol problems in the biological parents predicted drug abuse in offspring (Cadoret et al., 1986). This indicates that the liabilities to these disorders may share a considerable proportion of genes determining their variation. In a subsequent family history study, it was found that abuse of nonal- coholic substances was significantly greater in probands with family histories of drug abuse than in those with a family history of alcoholism (Meller et al., 1988). This finding points to certain specificity of the liabilities to alcohol and drug abuse. Importantly, environmental factors such as divorce and psychiatric disturbance in the adoptive family were associated with increased drug abuse in adoptees (Cadoret et al., 1986).

Parallel results from twin studies of alcoholism (Kaij, 1960; Partanen et al., 1966; Gabrielli and Plomin, 1985; Pickens et al., 1991; McGue et al., 1992; Kendler et al., 1992) indicate that the concordance of MZ twins for alcohol use is significantly higher than for DZ twins. Based on twin studies, the estimates of the heritability of the liability to alcoholism reach 0.73 in males (McGue et al., 1992) and 0.61 in females (Kendler et al., 1992), varying for different definitions of the threshold phenotype. In males shared environment ap- peared to play a more important role in the variability of the liability compared to that of nonshared environ- ment. In contrast, only nonshared, unique, environment contributed the phenotypic variation in females. The findings on alcoholism are consistent with the data on the composition of the variance of the liability to drug abuse. Similar results were obtained regarding alcohol consumption (Jardine and Martin, 1984). In females, heritability was estimated at 0.56, with only nonshared environment contributing phenotypic variation. In males, heritability was 0.36, and 20% of phenotypic variance was accounted for by shared environment.

Beginning with the studies of Goodwin et al. (1973, 1974) on a Danish sample, it has been consistently shown that the risk for alcoholism in offspring of alcoholics is higher than in children of nonalcoholics even when they are separated from their biological parents early in life. The data even showed some trend for a decrease in the frequency of alcoholism in sons who lived with their alcoholic fathers: 17% of them became alcoholics vs. 25% of adopted-out sons of alco- holics (the latter being nearly 4 times the frequency of

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alcoholism among sons of nonalcoholics). Results from another adoption study, on a Swedish sample (Bohman et al., 1987; Cloninger et al., 1981), showed that alco- holism frequency was increased both in sons of fathers who were registered alcohol abusers (22.8 vs. 14.7% for sons of parents who were not registered as alcohol abusers) and alcohol abusing mothers (28.1 vs. 14.7%). There was no excess of alcohol abuse in daughters of all alcoholic biological fathers in the sample (3.5 vs. 2.8%). However, in daughters of alcohol-abusing mothers, the rate of alcohol abuse was significantly higher (10.3% when mothers were abusers and fathers were not, and 9.1% when both parents were alcohol abusers, vs. 2.8% in controls) (Bohman et al., 1981; Cloninger, 1990).

4. Heritability of temperament and personality

A significant genetic component has been consis- tently shown for variability in temperament and per- sonality characteristics. Thus, correlations between MZ twins reared apart (which give the direct estimate of broad sense heritability) range between 0.4-0.5 for personality traits measured by the Multidimensional Personality Questionnaire and California Psychological Inventory (Bouchard et al., 1990). Of the same order are the estimates of the additive genetic component of variance for the traits measured by the Eysenck Person- ality Questionnaire (Eaves et al., 1989; Pedersen et al., 1988). Significant estimates of heritability have also been derived from twin studies for the dimensions of locus of control and for Type A-like behaviors (Pedersen et al., 1989a,b) and from twin and adoption studies for scales measuring temperament (Plomin et al., 1988; Buss and Plomin, 1984; Neale and Stevenson, 1989).

Heritability of antisocial behavior has attracted con- siderable research and public interest. Adopted children of antisocial biological parents have an increased fre- quency of antisocial personality (ASP) as adults (Cadoret,, 1978). Twin studies have shown that concor- dance for criminality is higher in MZ twins than in DZ twins (Christiansen, 1970; McGuffin and Gottesman, 1984). The results of twin studies were consistent with the absence of gender differences in heritability or common environment in self-reported delinquent be- havior (Rowe, 1983) and criminality (i.e., the same familial factors determine variation in these traits in males and females) (Carey, 1992). Significant heritabil- ity (0.44) was estimated for the aggression scale of the Multidimensional Personality Questionnaire (MPQ) in a study which used both twins reared together and twins reared apart (Tellegen et al., 1988). This twin study also reported that the shared family environmen- tal component of phenotypic variation was remarkably low for almost all the traits measured by MPQ, except

social closeness. In contrast, the estimate of the contri- bution of unique or nonshared environment was at least as high as heritability. Consequently, since social closeness (e.g., Krueger et al., 1994) as well as aggres- sion are likely to be associated with antisocial behavior, both genetic and environmental variation may con- tribute to different dimensions of individual differences in antisocial behavior.

In the above cited study of MZ twins reared apart, heritability was shown to be around 0.42 for childhood antisocial symptoms and 0.29 for adult symptoms. This study also reported high genetic correlations between antisocial symptom counts and alcohol/drug abuse, ranging from 0.53, for adult antisocial symptoms and drug abuse, to 0.87, for childhood symptoms and drug abuse. It should be noted that these data suggest a high degree of commonality between the genes that con- tribute to variation in antisocial behavior and in the liabilities to alcoholism and drug abuse. This implies that assortment for either trait will have genetic impli- cations for the other.

Common genetic causes of variation may partially account for the frequently observed phenotypic associa- tion between antisocial behavior and the liabilities to psychoactive substance use disorders. Men with antiso- cial personality (ASP) are five times as likely to abuse drugs as those without, and in women the risk 12 times higher (Robins et al., 1991). The prevalence of ASP in alcoholics is 12 times higher than that in nonalcoholics in men and 29.6 times in women. The relationship between antisocial behavior and substance use disorder also involves aggression under intoxication. Alcoholics with high scores on measures of childhood aggression reported greater change in anger when drinking and more aggression when drinking than patients with low childhood aggression (Jaffe et al., 1988).

The data obtained in genetic studies suggest develop- mental and transgenerational continuity of antisocial behavior, which may be caused by both genetic and environmental factors. In fact, “antisocial personality is the only one [personality disorder] for which either onset in childhood (three symptoms before age 15) or continuity over time is specifically required” for diagno- sis (Robins et al., 1991, p. 259). Adoptive fathers of children with aggressive conduct disorder less often had antisocial personality disorder than the natural fathers of nonadopted children with this disorder, and the same trend was observed in mothers (Jary and Stewart, 1985). Parents of children with conduct disorder have a higher prevalence of both antisocial personality and alcohol abuse than parents of children without conduct disorder (Jary and Stewart, 1985; Lahey et al., 1988). Ninety-five percent of males having four or more adult ASP symptoms have had at least one childhood con- duct disorder (CD) symptom, and 76% have had three or more symptoms (Farrington, 1991). CD symptoms

MM. Vanyukov et al. /Drug and Alcohol Dependence 42 (1996) I-10 5

in childhood account for approximately 25% of the variation in adulthood ASP symptoms, and there is significant correlation between parental CD and ASP symptom counts and CD counts of their young children (Vanyukov et al., 1993, 1994). The predictive power of childhood antisocial behavior for adult antisocial per- sonality and substance abuse has been found to be similar in both sexes (Robins and Price, 1991). In turn, conduct disorder is associated with an increased risk for alcoholism, substance abuse and antisocial personality (Robins and Price, 1991). In drug abusers, early onset of antisocial behavior is associated with especially severe adult antisociality (Brooner et al., 1992). From the research conducted to date, it can be concluded that there is an association between personality features and the liability to substance abuse.

5. Assortative mating for the liability to substance abuse and for associated personality traits

The heritability of the liability to substance abuse and temperament/personality characteristics indicate that assortative mating for these traits could consider- ably influence the relationship between parental pheno- types and the expression of these traits in the offspring. Assortment may lead to, and maintain, the increase in both genetic and environmental (in the presence of cultural transmission) covariance between parents and their children.

Marital assortment on personality characteristics as- sociated with, and/or contributing to, the variability of the liability to substance abuse, may mediate the assort- ment for this trait, resulting in the increase in off- spring’s liability even in the absence of the manifest disorder in the parent(s). It has been shown that there is spousal similarity possibly caused by positive assort- ment on traits measured by the Eysenck Personality Questionnaire-extraversion (Buss, 1984; Mascie- Taylor and Vandenberg, 1988) inconsistency (Lie) (Mascie-Taylor and *Vandenberg, 1988; Eaves et al., 1989), and psychoticism (Eaves et al., 1989). Positive mate correlation was also found for almost all of the California Psychological Inventory scales (Buss, 1984; Swan et al., 1986) as well as for sensation-seeking (Farley and Davies, 1977; Farley and Mueller, 1978) which has been shown to be associated with antisocial behavior (Hesselbrock and Hesselbrock, 1992) and cor- relate with alcohol use (Zuckerman, 1972) and the liability to alcoholism in general (Cloninger et al., 1988).

Homogamy has also been found for various forms of psychopathology, including neuroses, affective disor- ders, phobia, hysteria, and antisocial personality (re- viewed by Merikangas, 1982). Parental concordance for alcoholism, for instance, has been shown to be associ-

ated with an increased risk for conduct disorder in childhood and antisocial personality disorder in adult- hood (Merikangas et al., 1985a,b). High phenotypic resemblance among spouses was found for wives of sociopathic males (spousal correlation, 0.70) and hus- bands of sociopathic females (0.60) (Cloninger et al., 1975). Importantly, the hypothesis of behavioral conta- gion among spouses as the cause of spousal phenotypic resemblance does not seem to be supported by the data obtained. Spousal differences in personality tend to increase rather than decrease as a function of marriage length (Buss, 1984). Homogamy for antisocial personal- ity was observed in an adoption study (Crowe, 1974). It is noteworthy that five of the six antisocial children of female offenders in this study also had antisocial fa- thers. A higher prevalence of both antisocial personality and alcohol abuse is found in parents of children with conduct disorder compared to parents of children with- out conduct disorder (Lahey et al., 1988). The liabilities to personality disorders, including antisocial personal- ity, have been shown to have significant heritabilities (reviewed by McGuffin and Thapar, 1992). Also, it has been found that both CD and ADHD are associated with the increased risk for the development of sub- stance abuse, and with the risk of psychopathology in general (Merikangas et al., 1988). Hence, it is plausible that assortment for the liability to substance abuse and for these liabilities (insofar as the latter are associated with the former) mutually increase parent-offspring re- semblance for these traits. This, in turn, may lead to further strengthening of the association between the liabilities to substance abuse and other behavior devia- tions due to an increase in both genetic and environ- mental correlations between the traits. Therefore, marital phenotypic assortment for personality traits, which might underlie assortment for the liability to substance abuse (that is, when there is secondary as- sortment for the liability) can be considered by itself an important potential risk factor.

Spousal similarity (suggesting the possibility of as- sortment) has been observed for the liability to alco- holism (Hall et al., 1983a,b; Penick et al., 1987; Jacob and Bremer, 1986; Moskalenko et al., 1992). Pheno- typic similarity of parents on this trait correlates not only with the risk of alcoholism in offspring, but also with the risk of antisocial personality/conduct disorder and attention deficit disorder (ADHD) (Penick et al., 1987; Moskalenko et al., 1992). In the latter study, significant differences were found in the frequencies of phenotypic classes: female alcoholic probands married predominantly alcoholics, while no male alcoholic proband had an alcoholic wife. Although the baseline rates of alcoholism among males and females necessary for correction in comparison are unknown for that population, the magnitude of the difference suggests that the likelihood of having a mate with a certain

6 h4.M. Vanyukov et al. / Drug and Alcohol Dependence 42 (1996) l-10

liability phenotype depends on the gender of the proband more than this is determined by the differ- ences in populational phenotypic distributions in males and females. Moreover, the probability of marrying an alcoholic for a female proband de- pended on her family history of alcoholism: 80% of husbands were alcoholic if at least one of the par- ents of the proband was affected, compared to 33% of husbands, when none of the alcoholic proband’s parents was affected.

In a study of the wives of male probands-sub- stance abusers and controls-29% had a diagnosis of substance abuse/dependence/polydrug abuse (Vanyukov et al., 1994). While 46% of the sample were the control probands’ families, only 10.5% of affected females were spouses of the control probands. This suggests high phenotypic resemblance between mates for the liability to substance abuse. Interestingly, not only quantitative, but also qualita- tive homogamy was observed. The wife’s addiction phenotype was specific for the group of abusers her husband belonged to: while spouses of substance abusing probands abused or were dependent on a variety of drugs, including alcohol (25%) opioids (17%), marijuana (13%) sedatives (6%), hallucino- gens (4%), amphetamines (3%), and cocaine (2%) only alcohol dependence or abuse were diagnosed among the wives of alcoholic (alcohol abuse/depen- dence only) probands (22%). In addition to the usual significant resemblance for IQ and education level, spouses also showed similarity for the Multidi- mensional Personality Questionnaire measures of alienation (0.45, P < O.OOl), traditionalism (0.38, P < O.OOl), and negative affectivity (0.35, P < 0.001) (Vanyukov et al., 1994). These characteristics were also associated with the liability to substance abuse.

Significant correlations between spousal antisocial behavior measured as retrospective conduct disorder and antisocial personality symptom counts were jointly estimated from clinically ascertained and con- trol samples using a minimum chi-squared fit func- tion (Vanyukov et al., submitted). The data suggest that spousal similarity for the liability to substance abuse may be due to direct (primary) homogamy for this trait or secondary to (mediated by) homogamy for antisocial behavior. To test a hypothesis that all spousal similarity for antisocial behavior is caused by homogamy for substance abuse, an ascertainment correction procedure was used (Roy et al., in press). The results obtained suggest that observed spousal similarity in the presence/absence of substance abuse disorder cannot be accounted for by direct ho- mogamy for antisocial behavior, while the opposite can be true.

6. Methodological approaches to studying mate similarity

To test hypotheses about sources of homogamy, a highly genetically informative twin-family design can be used (e.g., Neale and Cardon, 1992; Truett et al., 1994). However, a simpler method, directed specifically to studying the relations of different traits in the determi- nation of spousal similarity and based on the analysis of covariance matrix for spouses, which does not re- quire an extended genetic design of twin-family or adoption study, can also be employed (Neale and McArdle, 1990). Particularly, linear structural equation analysis can be applied to test models explaining inter- spousal correlations. Direct (primary) homogamy for personality traits and for the liability to substance abuse, and secondary assortment for the liability to substance abuse (no direct homogamy for the presence/ absence of substance abuse) are alternatively assumed as nested models, for which the goodness-of-fit statistics are compared.

It is reasonable to model assortment separately for male and female probands. Hall et al. (1983a) note that using a linear correlational approach for studying mar- ital assortment may fail to uncover interspousal pheno- typic associations because of potential moderation of this association due to phenotype-sex interaction. In other words, phenotype-sex interactions concomitant to social norms or other factors operating differentially in males and females may cause asymmetry of assortment. For example, an increase in affective illness, which is more common in women, has been found in wives of affected males but not in husbands of affected females (Merikangas, 1982). Men abstaining from substance abuse may be more restricted in their mate choice to their own phenotypic class than women abstaining from substance abuse, while substance-abusing women may be more restricted in their choice to their own phenotypic class than men. While the relationship be- tween spousal phenotypes in the population is esti- mated by a single correlation coefficient, this coefficient does not give a notion of the form of the bivariate distribution. If no heterogeneity due to gender is found, the gender groups can be combined.

Conditional paths (Carey, 1986) are used to denote assortment. A conditional path is a measure of direct homogamy regarding two mate variables as opposed to other possible sources of the observed correlation be- tween them due to homogamy for correlated variables. The conditional paths approach provides for studying the structure of mate relationship by the comparative testing of different submodels which explain observed correlations among mates’ variables by primary and/or secondary homogamy. The models can be fitted to the covariance matrices using structural equation modeling software such as the Mx program (Neale, 1991) which

MM. Vanyukov et al. 1 Drug and Alcohol Dependence 42 (1996) l-10 7

allows for an economic and flexible formulation of the model by enabling the user to specify arbitrary matrix operations.

The possibility of behavior contagion can be assessed by studying the relationship between the degree of similarity and the duration of cohabitation, and, for categorical diagnoses, by contrasting the dates of onset of the disorder and initiation of interpersonal relation- ship. Hierarchical multiple regression can be used to test the relationship between the length of cohabitation and spousal similarity (Price and Vandenberg, 1980). In essence, this analysis is designed to test the effect of moderation of the relationship between the phenotypes of mates by age, which is treated as a moderator, while the phenotype of one mate is treated as a dependent variable, and the phenotype of the other mate, as an independent variable. A moderator is defined as a variable that affects the direction and/or strength of the relation between an independent variable and a depen- dent variable (Baron and Kenny, 1986). The duration of cohabitation is entered in the regression equation first, the phenotypic value of one mate is entered as the second step, and the cohabitation length x phenotype interaction term is entered last. A significant increment in multiple R caused by the interaction term indicates a cohabitation effect (contagion).

An indication that spousal resemblance for the liabil- ity to substance abuse is not entirely due to contagion would be a non-zero correlation between the spouse’s siblings and the siblings of the other spouse. However, under phenotypic assortment, this correlation is pre- dicted to be the product of the correlation between one spouse and his/her sibling, the correlation between the other spouse and her/his sibling, and the copath be- tween the spouses (which is equal to marital correlation under pure direct phenotypic assortment) (Cloninger, 1980). Therefore, the sample size needed to estimate this correlation with adequate statistical power may be extremely large and unfeasible to attain. On the other hand, social homogamy models typically predict this ‘second in law’ correlation to be close or equal to the marital correlation.

While numerous personality variables have not been shown to demonstrate convergence (contagion) between spouses (Price and Vandenberg, 1980; Caspi and Her- bener, 1990, 1993), increase in spousal similarity was observed for alcohol consumption (Price and Vanden- berg, 1980).

To test whether mate selection for the liability to substance abuse is purely determined by social back- ground (social homogamy) or phenotypic assortment, scaling tests (Heath and Eaves, 1985) using correlations between spouses, between spouses and spouses’ siblings, and between spouses’ siblings can be used. It has been shown that data on pairs of siblings and their spouses are sufficient to tests the hypotheses of pure social

homogamy or pure phenotypic assortment. Namely, according to the scaling tests, under the model of pure social homogamy, expected correlations (the notations shown are as used by Heath and Eaves, 1985) between the spouses and between the spouse his/her spouse’s sibling (sib-in-law, affined sibling) are equal (pb = pi,). Under the model of pure phenotypic assortment with no measurement error, expected correlations between spouses and their affined siblings are equal to the product of correlation between spouses and their sib- lings and correlation between spouses (p ;, = pip 6). Also, the expected correlation between the siblings of one spouse and the siblings of the other spouse equals the product of the expected correlation between the spouse and the spouse’s sibling and the squared correla- tion between the spouses; it also equals the product of the expected correlation between spouses and the corre- lation between spouses and their affined siblings (phS = PtPs ’ ‘2 = pisp:). Under the model of phenotypic assortment with measurement error, the ratio of the expected correlation between the spouse and his/her affined sibling to the expected correlation between the spouse and his/her cognate sibling is equal to the ratio of the expected correlation between the spouse’s sib- lings and the siblings of the other spouse to the ex- pected correlation between the spouse and his/her affined sibling (p Jp; = p :,/p &).

Resolution of the origins of marital resemblance could have both research and practical implications as well as pose new important questions. Failure to take assortment into account can lead, in twin research, to overestimation of shared environmental influences and underestimation of additive genetic variance when the DZ twin correlation is greater than half the MZ corre- lation (Allison et al., 1996). Allison and co-authors give an example where taking into account phenotypic as- sortment as low as 0.13 changes additive genetic and common environment estimates from 70 to 78% and from 2 to lo%, respectively.

With the heritability of 0.5 and correlation between spouses of 0.5, the eventual (at equilibrium) increase in phenotypic variance for a multifactorial trait is esti- mated to be 21% (Crow and Felsenstein, 1968). For a population with 5% affected individuals (as is, approxi- mately, the case for substance abuse) this would be equivalent to a shift of the threshold to the left from its position on the z-scale of the standard normal distribu- tion at 1.645 to 1.36 and an increase in the frequency of the disorder to 8.7%. Considering that assortment for the liability to substance abuse may be higher than 0.5 (0.6-0.9) (Vanyukov et al,, submitted), this increase may be even larger. Therefore, the mechanisms of assortment may partly account for the secular trends observed for substance abuse. Particularly, increase in lifetime prevalences of alcoholism and decrease in its age of onset in younger generations (Reich et al., 1988)

8 M.M. Vanyukov et al. /Drug and Alcohol Dependence 42 (1996) l-10

could be partly caused by assortment. This kind of ‘anticipation,’ one expression of which is the decreased age of onset, could also lead to increased liability to polysubstance use, deeper involvement with more dan- gerous substances, and more severe drug dependence, and greater affectedness of females. Because of the associations existing between drug use and antisocial behavior, assortment for the liability to substance abuse could cause analogous anticipation in antisociality. This effect would be further exacerbated by phenotype- environment correlation (selection of environment promoting phenotype expression) and increase in anti- sociality concomitant to drug use environment. It is, therefore, important to know whether mate similarity for the liability to substance abuse is caused by direct or indirect assortment and sources of possible indirect assortment, as opposed to social homogamy and conta- gion. Such research has yet to be conducted.

The consequences of assortment mentioned can change the characteristics of the population only until an equilibrium is established. After that, heritability as well as other components of phenotypic variance should stabilize, unless assortment (or selection pres- sures) change. A test for that would be estimating assortment and heritability of the liability to substance abuse in consecutive different generations. If ho- mogamy for the liability to substance abuse is sec- ondary to that for other traits (such as antisociality), it would be necessary to obtain data on those traits in the genetic studies of substance abuse, which otherwise would be incomplete. Genetic consequences of assort- ment for these traits would also involve changes in the distributions of genotypes and phenotypes for the li- ability to substance abuse. This would have to be taken into account in various areas of genetic research, in- cluding the search for quantitative trait loci for the liability to substance abuse and associated traits.

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