Substance Use in World War II Veteran Twins: A Genetic Analysis

Dorit Carmelli, Gary E. Swan, and Dennis Robinette *

BACKGROUND

Significant contributions of genetic factors to variation in alcohol and tobacco consumption have been demonstrated repeatedly using a variety of study designs including monozygotic (MZ) and dizygotic (DZ) twin pairs, extended family studies, and adoption-based studies. Hughes 1 recently summarized a number of twin studies in which heritability estimates (the proportion of variance attributed to genetic factors) for tobacco use ranged from 0.28 to 0.84, with a mean of 0.53; heritability estimates for alcohol use ranged from 0.28 to 0.51, with a mean of 0.42. Other studies have reported heritability for coffee drinking in male twins in the range of 0.46 2 , 3 to 0.88. 4 Results from these studies, including our own analysis of a relatively small subset of the National Academy of Sciences-National Research Council (NAS-NRC) World War II Twin Registry, known as the NHLBI Twin Study, are summarized in Table 1 . We note from examination of Table 1 the relatively wide range of heritability estimates, which may have resulted from both the wide range in sample sizes that the studies were based on and the use of different measures of smoking, alcohol use, or coffee consumption.

*  

Dorit Carmelli, Ph.D., and Gary E. Swan, Ph.D., are with the Health Sciences Program, SRI International, Menlo Park, California. Dennis Robinette, Ph.D., is with the Medical Follow-up Agency, National Academy of Sciences, Washington, D.C. Correspondence to Dr. D. Carmelli, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA. This research was supported by Contracts N01-HC-55029 and N01-HC-85078 from the National Heart, Lung, and Blood Institute.



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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 Substance Use in World War II Veteran Twins: A Genetic Analysis Dorit Carmelli, Gary E. Swan, and Dennis Robinette * BACKGROUND Significant contributions of genetic factors to variation in alcohol and tobacco consumption have been demonstrated repeatedly using a variety of study designs including monozygotic (MZ) and dizygotic (DZ) twin pairs, extended family studies, and adoption-based studies. Hughes 1 recently summarized a number of twin studies in which heritability estimates (the proportion of variance attributed to genetic factors) for tobacco use ranged from 0.28 to 0.84, with a mean of 0.53; heritability estimates for alcohol use ranged from 0.28 to 0.51, with a mean of 0.42. Other studies have reported heritability for coffee drinking in male twins in the range of 0.46 2 , 3 to 0.88. 4 Results from these studies, including our own analysis of a relatively small subset of the National Academy of Sciences-National Research Council (NAS-NRC) World War II Twin Registry, known as the NHLBI Twin Study, are summarized in Table 1 . We note from examination of Table 1 the relatively wide range of heritability estimates, which may have resulted from both the wide range in sample sizes that the studies were based on and the use of different measures of smoking, alcohol use, or coffee consumption. *   Dorit Carmelli, Ph.D., and Gary E. Swan, Ph.D., are with the Health Sciences Program, SRI International, Menlo Park, California. Dennis Robinette, Ph.D., is with the Medical Follow-up Agency, National Academy of Sciences, Washington, D.C. Correspondence to Dr. D. Carmelli, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA. This research was supported by Contracts N01-HC-55029 and N01-HC-85078 from the National Heart, Lung, and Blood Institute.

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 Despite the findings suggestive of a significant role for genetic factors, behavioral scientists seem generally reluctant to acknowledge the contribution of these factors to appetitive behaviors that fall within the “normal” range of consumption. For example, neither the 1988 nor the 1989 Surgeon General's Report 5 , 6 mentions any of the studies cited above that show small but significant heritable components to smoking behavior. The reluctance to acknowledge the results from these studies may be related to the belief that genetic determinants imply a lack of modifiability. However, if genetic effects do play a role in smoking behavior, further studies that sort out these effects could lead to an increased understanding of why there continues to be a relapse problem among smokers who have recently quit, despite the most ardent and forceful efforts of public health specialists to change these behaviors. In the present paper, we hope to demonstrate the potential value of studying twins in general and, more specifically, of the NAS-NRC World War II Twin Registry, for examining issues related to the genetics of substance use. It is our belief that twin studies actually provide valuable opportunities for investigating the contribution of environmental influences on substance use behavior. For example, by comparing the life-long smoking behavior of genetically identical MZ twin pairs, it is possible to eliminate genetic variability, thereby creating a pure culture of nongenetic determinants--determinants that can be identified as being “environmental exposures” and “personal behaviors.” Once we have established that such environmental exposures during adult life are responsible for a behavior in question, appropriate changes in the environment could be recommended as an effective means of intervention. Apart from the power of the twin method to assess the roles of genetic and environmental factors of health behaviors during late adulthood, the NAS-NRC Twin Registry is noteworthy for several specific features. First, the cohort is sufficiently large to support powerful analyses; second, excellent longitudinal data are available on these subjects from military induction (ages 17 to 28 years) and during middle age; and, third, repeated information on an array of cardiovascular disease risk factors and health behaviors was collected on these subjects when they were 42 to 55 years old and repeated 10 years later by the administration of standardized epidemiological questionnaires. It is our intent in this report to present some preliminary results from a genetic analysis of smoking, alcohol use, and coffee consumption in the NAS-NRC Twin Registry. Our results support the conclusion that genetic factors contribute to the variation in substance use behaviors in late adulthood and that these behaviors are minimally influenced by shared environmental factors and the simultaneous occurrences of combinations of these behaviors.

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 THE NAS-NRC TWIN REGISTRY Figure 1 presents an overview of the sample on which the analyses presented in this chapter were performed. The NAS-NRC Twin Registry was developed originally on approximately 16,000 pairs of twins who were inducted into World War II and for whom medical records were available. All twins were born between 1917 and 1927. The original and current intent of the registry was the follow-up of the twins for eventual mortality so that genetic contributions to coronary heart disease and cancer could be determined. 7 The method by which zygosity was determined in the registry relied on twin self-report, which was confirmed in a subset through the use of fingerprint and blood analysis. 7 During 1969-72, approximately 5,000 twin pairs (MZ pairs = 2,390, DZ pairs = 2,571) completed a mailed questionnaire that was standardized to be similar to questionnaires used by the Swedish and Finnish Twin Studies. 8 The questionnaire requested information on a variety of variables, including substance use, diet, work history, and various illnesses. At the time of completion of the questionnaire, the mean age of the respondents was 49 years. SUBSTANCE USE IN THE NAS-NRC TWIN REGISTRY Substance use in the NAS-NRC Twin Registry and, for comparison purposes, that for the younger Finnish Twin Registry 9 are presented in Table 2 . The extremely high prevalence of ever smoking (81%) in the NAS-NRC Registry, compared with the Finnish Registry (62%) and with the general U.S. population, is noteworthy. The most probable explanation for this high prevalence is the twins' participation in World War II, during which cigarettes were dispensed routinely, free of charge, to all servicemen. It should also be noted that the NAS-NRC Registry consists of individuals drinking alcohol at levels equivalent to those found in the Finnish Registry and, with regard to coffee drinking, at levels somewhat lower than those of the twins from Finland. SUBSTANCE USE: ENVIRONMENTAL CORRELATES AND CO-OCCURENCE The computation of heritability estimates of appetitive behaviors, based on twin studies, is complicated by the fact that multiple nongenetic sources of variance underlie twin similarity or dissimilarity. Among these are age, sex, socioeconomic and marital status, and frequency of twin contact. 10 , 11 , 12 Another source of confounding variance lies in the fact that smoking, alcohol use, and caffeine consumption are correlated.

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 Evidence for the bivariate associations between these substance use behaviors, as reviewed by Istvan and Matarazzo, 13 reveals a consistent pattern for smoking, as opposed to nonsmoking, to be related to greater consumption of alcohol and, within smokers, for higher amounts of tobacco consumption to be related to more drinking. 14 , 15 , 16 , 17 Other large population-based studies 14 , 18 , 19 , 20 show moderate to strong associations between caffeine consumption and cigarette smoking in males. There is no evidence for an association between caffeine and tobacco consumption, but, as pointed out by Istvan and Matarazzo, 13 this finding is based on relatively few studies and the relationship warrants further investigation. The conclusion that use of these three substances is often related has led some to speculate that a common pathophysiological process may underlie their use. 18 , 21 However, as Istvan and Matarazzo 13 point out, with one recent exception, 22 no study exists that has investigated the use of these three substances simultaneously. From the perspective of behavioral genetics, these known relationships among the various substance use behaviors and their relationships to environmental factors present interesting problems for interpreting broad heritabilities derived for each behavior separately. Although recent studies do indicate the presence of significant heritability estimates for smoking and alcohol use 1 , 4 and caffeine consumption, 3 , 4 , 21 these analyses did not account for shared covariance. Only one study that we are aware of has attempted to investigate the genetics of combined heavy use of alcohol and tobacco. While finding no genetic effect for combined heavy use, the authors point out that this result may have been due to the small sample size of heavy users. 15 This represents another area in which the comparatively large sample size of a narrow age group of adults in the NAS-NRC Registry may eventually prove valuable. A first attempt to deal with the complexity of heritability analyses of appetitive behaviors is presented in the following analysis. Our primary objective was to control for the effects of environmental factors and covariance among appetitive behaviors while examining the heritability of each appetitive behavior individually. To our knowledge, this approach is new and has been reported only recently in a series of studies of the NHLBI Twin Study subsample. 23 , 24 STATISTICAL METHODS Analyses were directed at estimating the heritable components of smoking, alcohol use, and coffee consumption, both before and after taking into account the effects of other substance use, age, socioeconomic status, and a measure of occupational adjustment. Unadjusted and adjusted heritability estimates were calculated and compared to evaluate the

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 contributions of these variables to the confounding of genetic variance when each of the appetitive behaviors is examined separately. In this approach, the adjustment of smoking for the consumption of alcohol and/or coffee was accounted for at the individual level, whereas the heritability analysis was conducted on twins as pairs following these adjustments. Using this approach, individual differences in the joint behavior of smoking, alcohol use, and coffee consumption were reflected in the heritability estimates of the adjusted variables. Smoking status was based on the self-reported number of cigarettes ever smoked per day; ascertaining only current cigarette smoking consumption, as has been done in several earlier studies, is unsatisfactory in intrapair comparisons if the smoking durations are different within the pairs. For the smoking variable we therefore selected the daily average cigarette consumption for all the subjects who had been smoking, past and present. Alcohol consumption was determined from self-reported total number of drinks per week in a typical week at the time of assessment and included beer, wine, and cocktails. For each type of beverage, the reported consumption in glasses or bottles per month was converted into grams of absolute alcohol and summed to give an individual average consumption per month. Mean consumption of cups of coffee per day was used as a caffeine dose variable. A socioeconomic score was constructed using education and military rank. The occupational adjustment score included items related to changes in employment, occupation, the type of employment (subordinate vs. supervisory position), and the frequency of overtime work or additional employment. To determine the extent to which covariates were related to smoking and alcohol use, both univariate and multivariate analyses were performed. A linear regression was developed using each appetitive behavior as the dependent variable and related characteristics such as other substance use, age, and socioeconomic status as independent variables. Separate models for MZ and DZ twins were developed under the assumption that these covariates contribute differentially to twin similarity in the two zygosities. The derived multivariate models had two purposes: first, to determine the amount of variance explained by associated variables in the two groups of twins, and, second, to use the derived models to adjust the raw values for the contribution of these variables to the between-pair variability. The actual adjustments were carried out on twins as individuals. For example, amount ever smoked was regressed on use of alcohol and coffee, age, and occupational adjustment (see Table 3 ). Intraclass correlations and heritability estimates were calculated for the residual values and compared with the corresponding estimates calculated for the unadjusted raw values. 23 , 24

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 We used both intraclass correlation heritability estimates 25 and a path model approach 26 to estimate parameters representing the effects of genes and the environment. The models used were rMZ = H + C and rDZ = 0.5H + C, where rMZ and rDZ refer to MZ and DZ intraclass correlations, H refers to the effect of shared genes (i.e., heritability), and C refers to the effect of shared environment. It should be emphasized that the simplest classical twin design assumptions are made in these models: purely additive genetic effects, random mating, the absence of gene-environment correlations or interactions, and the same degree of environmental similarity for MZ and DZ pairs. Moderate failure to meet these assumptions may result in estimated parameters that do not have the simple interpretations intended. Nevertheless, provided the departures are not drastic and the data fit the model tested, meaningful conclusions may still be drawn from broad comparisons among different genetic and environmental models. The NAS-NRC data permit testing such models with H, C, or both constrained to be the same for each appetitive behavior against models that allow differences in H and C for the different appetitive behaviors. BIVARIATE ASSOCIATIONS BETWEEN SMOKONG, ALCOHOL USE, COFFEE CONSUMPTION, AND COVARIATES Table 4 presents the correlation matrix of the bivariate associations between smoking, alcohol use, coffee consumption, and demographic variables treating twins as individuals. As expected from previous research, we observe that alcohol use and coffee consumption were positively related to cigarette smoking. Daily coffee consumption was unrelated to the amount of alcohol consumed monthly. Age was negatively related to the number of cigarettes ever smoked per day but not to total amount of alcohol consumed monthly or to number of cups of coffee consumed daily. Socioeconomic status was positively associated with alcohol consumption and negatively related to the number of cigarettes ever smoked per day. Occupational adjustment was negatively associated with the number of cigarettes per day and the number of cups of coffee per day. Given these relationships, we developed separate models for adjustment for each of the appetitive behaviors. Table 3 presents these models in detail. GENETIC ANALYSES Raw measures of smoking, alcohol use, and coffee consumption showed significant differences in total variances; in some cases, we also observed differences in means as well as deviations from normality. When

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 a log transformation of the observed raw values was employed, the majority of these differences were eliminated. Smoking Estimates of genetic variance for the log-transformed amount of cigarettes smoked daily (unadjusted and adjusted) are presented in Table 5. Heritability estimates for unadjusted cigarette smoking are moderate, with the additive genetic component accounting for 52% of the total variance. After adjustment for covariates, this genetic component of variance was reduced to 42% of the total variance. Estimates of heritability were highly significant both before and after adjustment, and shared environmental effects among twins did not contribute to twin similarities. Alcohol The heritability estimate of the log-transformed alcohol variable was moderate and significant, with 36% of the total variance attributable to an additive genetic effect. The estimate of an effect of shared environment was 15% of the variation in alcohol consumption. Adjusting the amount of alcohol consumed for smoking and related covariates lowered the heritability estimate of alcohol consumption to 30% and removed the effect of shared environment. Coffee Although average coffee consumption was significantly higher in DZ than MZ twins, this difference was eliminated by the log transformation and the adjustment for covariates. The heritability estimate for coffee consumption was 44% and highly significant. Adjusting coffee for smoking had no effect on this estimate, and the shared environmental component was not significant. DISCUSSION In this analysis we have demonstrated an epidemiological approach to the investigation of twin similarity in smoking, alcohol use, and coffee consumption. Our approach takes into account confounding and shared covariance between appetitive behaviors, as well as selected demographic variables and their differential impact on MZ and DZ similarity. Because this approach treats the heritability analysis of substance use as essentially a multivariate problem (as opposed to its traditional treatment as a univariate problem), it provides a method to account for the confounding of estimates of heritability of smoking, alcohol use, and coffee use when analyzed separately.

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 Our results showed unadjusted heritability estimates for smoking and alcohol to be consistent with previously published research. For smoking, the estimate obtained in the present study was 0.52, which is identical to the average cited by Hughes. 1 For alcohol use, the unadjusted heritability estimate was 0.36, somewhat lower than the mean value of 0.42 reported by Hughes. Although the adjustment process resulted in heritability estimates that were somewhat lower than the unadjusted estimates, all estimates remained significant. The apparent robustness of the genetic component in smoking, alcohol use, and coffee consumption, even after the adjustment for covariates, supports the general conclusion that each of the substance use behaviors is, in part, genetically determined. Genetic analyses of cardiovascular risk factors have shown a similar robustness under conditions of adjustment for environmental covariates for HDL and LDL cholesterol, triglycerides, relative weight, and some measures of Type A behavior 24 but not for systolic and diastolic blood pressure. 27 Our results also suggest that the most important source of nongenetic variation for each of the appetitive behaviors in late adulthood is nonshared environmental effects. When computed as the variance remaining after genetic and shared environmental effects are taken into account, these estimates range from 0.57 to 0.63. Even though these estimates include measurement error, they account for a substantial proportion of the total variation. Moreover, in all cases the adjustment for shared covariance among these behaviors resulted in an increase of the nonshared variance component unique to the individual. For alcohol consumption, the 15% of shared variation observed before adjustment was reduced to zero after adjustment. This means that being reared in the same family and sharing the same home environment do not contribute to similarity in alcohol use later in life. Moreover, the magnitude of such individual nonshared environmental variance components was similar for each of the smoking, alcohol use, or coffee consumption behaviors. Other investigators 28 have argued for a multivariate genetic path model approach that allows the estimation of the separate and joint effects of genes and environment that underlie the covariation of symptoms or behaviors in twin pairs. This approach, which we believe may further contribute to the understanding of substance use behaviors, is different from that used in the present analysis. We strongly believe that it is important to explore the effects of confounding variables before fitting causal models based on assumptions that these effects have no influence on how genes and environment interact. Because of the high prevalence of smoking and the comparatively high levels of heavy alcohol consumption, the NAS-NRC Twin Registry provides a unique opportunity to examine issues surrounding substance use

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 at various levels and frequencies. More recently, results from a 1981 survey of alcohol consumption patterns in the Australian Twin Register 11 , 12 revealed that adult alcohol consumption patterns are determined by separate Abstinence, Quantity, and Frequency dimensions. Moreover, for the latter two dimensions there were substantial genetic effects, whereas twin correlations for Abstinence were consistent with nongenetic determination of this dimension. What has yet to be ascertained is whether there exist low levels of alcohol or tobacco use that are the equivalent of total abstinence, and that are environmentally determined. To address such questions, large cohorts of twins with normal ranges of consumption are needed. The NAS-NRC Twin Registry has these unique features. Finally, this study has several limitations that the reader should bear in mind. First, this is a heritability analysis of substance use, not of addiction. Second, our analysis included only male twins who were somewhat older than samples on which previous heritability analyses have been conducted. It would be interesting to see whether the effects of adjustment generalize to younger males and to females. Most important, it is, at this point, equally plausible to suggest that differences in smoking, alcohol use, or coffee consumption behavior cause or result from twin similarity or dissimilarity on the variables used in this analysis. Several aspects of the data also limit inferences regarding the differential impact of contact between the twins on twin similarities of appetitive behaviors. For example, although we may have superficial knowledge of the extent of the interaction between twins, we have no knowledge of the type and quality of the interaction. Moreover, we do not know whether any early environmental differences existed between MZ and DZ twins, or whether there were differences in parental behavior that could account for present differences. We hope to address these issues in future analyses. REFERENCES 1. Hughes JR. Genetics of smoking: A brief review Behavior Therapy , 17 : 335-345 1986 2. Kaprio J Koskenvuo M Sarna S Cigarette smoking, use of alcohol, and leisure-time physical activity among same-sexed adult male twins In: Gedda L, et al.(Eds.) Twin Research 3: Epidemiological and Clinical Studies . New York : Alan R. Liss pp. 37-46 1981 3. Partanen J Brunn K Markkanen T Inheritance of Drinking Behavior: A Study of Intelligence, Personality and Use of alcohol of Adult Twins . Oslo : The Finnish Foundation for Alcohol Studies 1966 4. Pedersen N Twin similarity for usage of common drugs In: Gedda L Parisi P Nance WE (Eds.), Twin Research 3: Part C, Epidemiological and Clinical Studies . New York : Alan R. Liss pp. 53-59 1981

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 5. Department of Health and Human Services The health consequences of smoking: Nicotine addiction Rockville, Maryland : U.S. Public Health Service. DHHS (CDC) 88-8406 1988 6. Department of Health and Human Services Reducing the health consequences of smoking: 25 years of progress . Rockville, Maryland : U.S. Public Health Service, DHHS (CDC) 89-8411 1989 7. Jablon S Neel JV Gershowitz H Atkinson GF The NAS-NRC twin panel: Methods of construction of the panel, zygosity diagnosis, and proposed use American Journal of Human Genetics , 19 : 133-161 1967 8. Cederlof R Epstein FH Friberg L Hrubec Z Radford EP Twin registries in the study of chronic disease Acta Medica Scandinavica , Supp. 523 1971 9. Kaprio J Koskenvuo M Artimo M Sarna S Rantasalo I Baseline Characteristics of the Finnish Twin Registry. Section I: Materials, Methods, Representativeness, and Results for Variables Special to Twin Studies . Helsinki, Finland : Department of Public Health Science M47 1979 10. Kaprio J Koskenvuo J Langinvainio H Romanov K Sarna S Rose RJ Genetic influences on use and abuse of alcohol: A study of 5,638 adult Finnish twin brothers Alcoholism: Clinical and Experimental Research , 11 : 349-356 1987 11. Jardine R Martin NG Causes of variation in drinking habits in a large twin sample Acta Geneticae Medicae et Gemellologiae , 33 : 435-450 1984 12. Heath AC Jardine R Martin NG Interactive effects of genotype and social environment on alcohol consumption in female twins Journal of Studies on Alcoholism , 50(1) : 38-48 1989 13. Istvan J Matarazzo JD Tobacco, alcohol, and caffeine use: A review of their interrelationships Psychological Bulletin , 95 : 301-326 1984 14. Friedman GD Klatsky AL Siegelaub AB McCarthy NM Kaiser-Permanente epidemiological study of myocardial infarction: Study design and results for standard risk factors American Journal of Epidemiology , 99 : 101-116 1974 15. Kaprio J Hammar N Koskenvuo M Floderus-Myrhed B Langinvainio H Sarna S Cigarette smoking and alcohol use in Finland and Sweden: A cross-national twin study International Journal of Epidemiology , 11 : 378-386 1982 16. Reynolds I Harnas J Gallagher H Bryden D Drinking and drug-taking patterns of 8,516 adults in Sydney Medical Journal of Australia , 2 : 782-785 1976 17. Cummins RO Shaper AG Walker M Wale CJ Smoking and drinking by middle-aged British men: Effects of class and town of residence British Medical Journal , 283 : 1497-1502 1981 18. Dawber TR Kannel WB Gordon T Coffee and cardiovascular disease: Observations from the Framingham study New England Journal of Medicine , 291 : 871-874 1974 19. Prineas RJ Jacobs DR Crow RS Blackburn H Coffee, tea, and VPB Journal of Chronic Diseases , 33 : 67-72 1980 20. Hrubec Z. Coffee drinking and ischemic heart disease Lancet , 1 : 583 1973 21. Kaprio J Koskenvuo M A prospective study of psychological and socioeconomic characteristics, health behavior and morbidity in cigarette smokers prior to quitting compared to persistent smokers and non-smokers Journal of Clinical Epidemiology , 41(2) : 139-150 1988 22. Carmody TP Brischetto CS Matarazzo JD O'Connell RP Connor WE Co-occurrent use of cigarettes, alcohol, and coffee in healthy, community-living men and women Health Psychology , 4(4) : 323-335 1985 23. Swan GE Carmelli D Rosenman RH Fabsitz RR Christian JC Smoking and alcohol consumption in adult male twins: Genetic heritability and shared environmental influences Journal of Substance Use , 2 : 39-50 1990

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 24. Carmelli D Rosenman RH Chesney MA Fabsitz R Borhani N Genetic heritability and shared environmental influences of Type A measures in the NHLBI Twin Study American Journal of Epidemiology , 127 : 1041-1052 1988 25. Falconer DS The inheritance of liability to certain diseases estimated from the incidence among relatives Annals of Human Genetics , 29 : 51-76 1965 26. Eaves LJ The utility of twins In: (Ed.), Genetic Basis of the Epilepsies . New York : Raven Press 1982 27. Austin MA King MC Bawol RD Hulley SB Friedman GD Risk factors for coronazy heart disease in adult female twins Epidemiology , 125 : 308-318 28. Heath AC Neale MC Hewitt JK Eaves LJ Fulker DW Testing structural equation models for twin data using LISREL Behavior Genetics , 19 : 9-35 1989

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 This page in the original is blank.

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 FIGURE 1 THE NAS-NRC TWIN REGISTRY

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 TABLE 1 HERITABILITY ESTIMATES FOR THE USE OF VARIOUS SUBSTANCES IN TWIN STUDIES FROM FINLAND, SWEDEN, AND THE UNITED STATES       Heritability a Study Sample Size (Twin Pairs) Country of Origin Tobacco Alcohol Caffeine Partanen et al. 3 902 Finland 0.28 0.47 0.46 Pedersen 4 137 Sweden 0.84 0.28 0.88 Kaprio et al. 2 5,044 Finland 0.46 0.51 0.46 Swan, Carmelli, et al. 23 [NHLBI Twins] 360 USA 0.52 0.60 a Proportion of total variance attributed to additive genetic effects. Note: Adapted from Hughes. 1 TABLE 2 SUBSTANCE USE IN THE NAS-NRC AND FINNISH TWIN REGISTRIES Substance Use NAS-NRC Registry Finnish Registry Smoking Nonsmoker 19.1% 38.1% Current smoker 58.7 42.5 Former smoker 22.2 19.4 Alcohol use (g/month) 0 – 250 46.7 47.7 251 – 500 14.4 25.8 > 500 38.9 26.5 Coffee drinking (cups/day) 0 11.0 6.1 1–5 66.1 51.0 > 6 22.9 43.9

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 TABLE 3 MODELS FOR ADJUSTMENT a , b CIGSDAY = α + β1 ALCOHOL + β2COFFEE + β3AGE + β4OCCADJ (1) ALCOHOL = α + β1 CIGSDAY + β2COFFEE + β3AGE + β4SOCEC (2) COFFEE = α + β1 CIGSDAY + β2ALCOHOL + β3OCCADJ (3) a Adjustment was done within zygosity group. b Adjusted variables are Student-t residuals from equations (1) -(3). TABLE 4 CORRELATIONS AMONG APPETITIVE BEHAVIORS AND SOCIODEMOGRAPHIC VARIABLES   Smoking Coffee Age Occupational Adjustment Socioeconomic Status Alcohol 0.224 (0.021 ) (−0.018) (0.013) 0.081 Smoking —— 0.332 −0.047 −0.048 −0.035 Coffee   —— (−0.015) −0.036 (−0.015) Age     —— (0.012) (−0.034) Occupational adjustment       —— 0.049 Note: Values in parentheses are not significantly different from zero.

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Epidemiology in Military and Veteran Populations: Proceedings of the Second Biennial Conference March 7, 1990 TABLE 5 GENETIC ANALYSES OF CIGARETTE SMOKING, ALCOHOL USE, AND COFFEE CONSUMPTION WITH AND WITHOUT ADJUSTMENT FOR COVARIATES   Intraclass Correlations Genetic Variance Individual Environment Shared Environment Substance Use MZ DZ H E C Smoking Log (cig) 0.50 0.24 0.52 0.50 (−0.02) Adjusted 0.38 0.17 0.42 0.62 (−0.04) Alcohol Log (dose) 0.51 0.33 0.36 0.49 0.15 Adjusted 0.22 0.37 0.30 0.63 (0.07) Coffee Log (dose) 0.42 0.21 0.44 0.54 (0.02) Adjusted 0.43 0.22 0.42 0.57 (0.01) Note: Values in parentheses are not significantly different from zero.