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The transmission of alcoholism
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sive, and even polygenic mission.
ABSTRACTS
mechanisms
of trans-
X-Linked Dominant Transmission in ManicDepressive Illness (Linkage Studies With Color Blindness). Ronald R. Fieve, M.D., Julien Mendlewicz, M.D., John D. Rainer, M.D., and Joseph Fleiss, Ph.D. New York State Psychiatric Institute, New York, N.Y. Heredity has been shown to be an important contributing factor in the etiology of manicdepressive psychosis. Although a genetic basis has been demonstrated for bipolar illness, the mode of transmission is still unknown, the main controversy being between single gene and polygenic inheritance. Winokur has proposed that a dominant gene located on the X-chromosome is involved in the transmission of manic-depressive illness. This hypothesis is supported by observations that bipolar illness often runs in successive generations, that the sex ratio for this illness is about two females for one male, and that father-son transmission is rarely observed by most investigators. In the present study, we report on nine informative families assorting for protan or deutan color blindness (recessive X-linked markers) and manicdepressive illness. The probands and their families were all from a sample of over 100 carefully diagnosed manicdepressive patients consecutively admitted to the Lithium Treatment and Research Clinic at the New York State Psychiatric Institute. The family history study method was used to evaluate the distribution of psychopathology in these families. Close linkage was found between the loci for manicdepressive illness and protan color blindness. Linkage between the locus for manic-depressive illness and the locus for deutan color blindness was slightly less close, but statistically significant.
Alcohol Problems in Adoptees Raised Apart from Alcoholic Parents. Donald W. Goodwin, M.D., Drinking practices and problems, plus a wide range of other life experiences, were studied in a group of 55 men who had been separated from their biologic parents early in life where one parent had a hospital diagnosis of alcoholism. Compared to a matched control group of adoptees, significantly more of them had a history of drinking problems and psychiatric treatment. The two groups did not differ with regard to other forms of psychopathology, such
as depression or character disorders. Children of alcoholics had three times the divorce rate of controls. Apart from alcohol problems and divorce, the two groups did not differ significantly with regard to any other variable studied. The adoptive parents of index and control subjects were of similar socioeconomic class and had similar rates of alcoholism and other psychiatric disorders. These findings suggest that genetic factors may play a role in the development of alcohol problems. The Transmission of Alcoholism. T. Reich, G. Winokur, and J. Mullaney, Washington University School of Medicine, St. Louis, MO. University of Iowa College of Medicine, Iowa City, Iowa, Washington University School of Meditine, St. Louis, MO. A number of studies of the families of alcoholics are available that point to alcoholism as a familial disease thay may be transmitted from parent to offspring. An estimate of the prevalence of alcoholism among the adopted-out offspring of alcoholic probands shows that biologic factors play an important role in the transmission of this disorder. This finding is supported by studies of the half-sibs of alcoholics reared both in the presence of and in the absence of’ an alcoholic parent. Since cultural and social class variables are also important determinants of this behavior, it may be safely concluded that both biologic and environmental factors are involved in the transmission of alcohol addiction, although the way in which those factors interact and the importance of each is unknown. In this paper, the degree to which alcoholism is familial is assessed by a comparison of the prevalence of alcoholism among the relatives of alcoholics with age-adjusted population prevalences drawn from a national survey of problem drinking reported by Cahalan. The multifactorial model of inheritance is used for the analysis, enabling an estimate of the correlation between relatives to be made without requiring assumptions about the cause of the similarity between them. This correlation combines the population and family data into a single value which expresses the increased similarity between relatives when compared with the appropriate population prevalence, and is a measure of the degree to which the disorder clusters in families. Different populations and different disorders can therefore be compared on the same scale, even if the population prevalences vary.
ABSTRACTS
Data for the analysis are drawn from a study of 5 10 firstdegree relatives of 259 alcoholic inpatients. Both the probands and their relatives were systematically examined by means of an extensive structured interview. The correlation between first-degree relatives was found to be 0.36 + 0.05 among whites and 0.49 * 0.07 among blacks, indicating that between-family sources of variation for each race are extremely important features of this disorder. The between-family factors responsible for the transmission of the disorder probably include both genetic and environmental influences. The relative importance of the transmission can be assessed by comparison with other familial disorders, and alcoholism appears to be more familial than peptic ulcer, diabetes, and essential hypertension. Alcoholism is approximately four times as common in males as females. The prevalence in males is estimated as 11.4% and in females as 2.9% in a population whose age is comparable to that of the relatives of the alcoholic probands (Cahalan). The prevelance in the male relatives of white male and female probands is 36% and 32%; and the prevalence in their female relatives is 6.4% and 6.7%, respectively. In order to ascertain whether the great preponderance of males is due to transmissible factors, estimates of the correlation between males and between females are computed separately. Among whites, the correlation between males (male probands and male relatives) is 0.53 _+0.05 and between females is 0.08 _C 0.10, a significant difference. The hypothesis that the difference is due to transmitted factors is tested by hypothesizing that it is not transmitted. The multifactorial model is then used to predict the correlation between probands and relatives of the opposite sex from the
93
correlations between same-sexed probands and relatives. The predicted value of the correlation between opposite-sexed relatives is 0.31 and the observed value is 0.28 t 0.06. This finding strongly suggests that alcoholism in males and alcoholism in females does not run in different families. The decreased correlation between female probands and relatives (as compared to males) is equal to that expected from the smaller proportion of affected females in the general population. With respect to the presence or absence of alcoholism, the genotypes of male and female alcoholics do not differ since they are equally able to transmit the disorder. The phenotypes of male and female alcoholics are different. Since the phenotype consists of both genotypic and environmental elements, environmental factors (e.g., exposure to heavy drinking) are sufficient to explain the difference in the prevalence of alcoholism in males and females. Furthermore, these environmental factors are not familial. Analysis of data obtained from black families leads to a similar conclusion. The multifactorial model of disease transmission appears to be a powerful device for the analyses of population and family data without requiring genetic assumptions which have led to such acrimony in the past. With respect to alcoholism, our results show that (1) among black or white populations alcoholism is familial to a large degree; (2) alcoholism in males and alcoholism in females is not transmitted independently; and (3) in spite of the phenotypic difference between male and female alcoholism (as shown by the different population prevalences), the genotypes of male and female alcoholics do not differ. This suggests that the large sex effect in this disorder can be explained by environmental sources of variation.
sive, and even polygenic mission.
ABSTRACTS
mechanisms
of trans-
X-Linked Dominant Transmission in ManicDepressive Illness (Linkage Studies With Color Blindness). Ronald R. Fieve, M.D., Julien Mendlewicz, M.D., John D. Rainer, M.D., and Joseph Fleiss, Ph.D. New York State Psychiatric Institute, New York, N.Y. Heredity has been shown to be an important contributing factor in the etiology of manicdepressive psychosis. Although a genetic basis has been demonstrated for bipolar illness, the mode of transmission is still unknown, the main controversy being between single gene and polygenic inheritance. Winokur has proposed that a dominant gene located on the X-chromosome is involved in the transmission of manic-depressive illness. This hypothesis is supported by observations that bipolar illness often runs in successive generations, that the sex ratio for this illness is about two females for one male, and that father-son transmission is rarely observed by most investigators. In the present study, we report on nine informative families assorting for protan or deutan color blindness (recessive X-linked markers) and manicdepressive illness. The probands and their families were all from a sample of over 100 carefully diagnosed manicdepressive patients consecutively admitted to the Lithium Treatment and Research Clinic at the New York State Psychiatric Institute. The family history study method was used to evaluate the distribution of psychopathology in these families. Close linkage was found between the loci for manicdepressive illness and protan color blindness. Linkage between the locus for manic-depressive illness and the locus for deutan color blindness was slightly less close, but statistically significant.
Alcohol Problems in Adoptees Raised Apart from Alcoholic Parents. Donald W. Goodwin, M.D., Drinking practices and problems, plus a wide range of other life experiences, were studied in a group of 55 men who had been separated from their biologic parents early in life where one parent had a hospital diagnosis of alcoholism. Compared to a matched control group of adoptees, significantly more of them had a history of drinking problems and psychiatric treatment. The two groups did not differ with regard to other forms of psychopathology, such
as depression or character disorders. Children of alcoholics had three times the divorce rate of controls. Apart from alcohol problems and divorce, the two groups did not differ significantly with regard to any other variable studied. The adoptive parents of index and control subjects were of similar socioeconomic class and had similar rates of alcoholism and other psychiatric disorders. These findings suggest that genetic factors may play a role in the development of alcohol problems. The Transmission of Alcoholism. T. Reich, G. Winokur, and J. Mullaney, Washington University School of Medicine, St. Louis, MO. University of Iowa College of Medicine, Iowa City, Iowa, Washington University School of Meditine, St. Louis, MO. A number of studies of the families of alcoholics are available that point to alcoholism as a familial disease thay may be transmitted from parent to offspring. An estimate of the prevalence of alcoholism among the adopted-out offspring of alcoholic probands shows that biologic factors play an important role in the transmission of this disorder. This finding is supported by studies of the half-sibs of alcoholics reared both in the presence of and in the absence of’ an alcoholic parent. Since cultural and social class variables are also important determinants of this behavior, it may be safely concluded that both biologic and environmental factors are involved in the transmission of alcohol addiction, although the way in which those factors interact and the importance of each is unknown. In this paper, the degree to which alcoholism is familial is assessed by a comparison of the prevalence of alcoholism among the relatives of alcoholics with age-adjusted population prevalences drawn from a national survey of problem drinking reported by Cahalan. The multifactorial model of inheritance is used for the analysis, enabling an estimate of the correlation between relatives to be made without requiring assumptions about the cause of the similarity between them. This correlation combines the population and family data into a single value which expresses the increased similarity between relatives when compared with the appropriate population prevalence, and is a measure of the degree to which the disorder clusters in families. Different populations and different disorders can therefore be compared on the same scale, even if the population prevalences vary.
ABSTRACTS
Data for the analysis are drawn from a study of 5 10 firstdegree relatives of 259 alcoholic inpatients. Both the probands and their relatives were systematically examined by means of an extensive structured interview. The correlation between first-degree relatives was found to be 0.36 + 0.05 among whites and 0.49 * 0.07 among blacks, indicating that between-family sources of variation for each race are extremely important features of this disorder. The between-family factors responsible for the transmission of the disorder probably include both genetic and environmental influences. The relative importance of the transmission can be assessed by comparison with other familial disorders, and alcoholism appears to be more familial than peptic ulcer, diabetes, and essential hypertension. Alcoholism is approximately four times as common in males as females. The prevalence in males is estimated as 11.4% and in females as 2.9% in a population whose age is comparable to that of the relatives of the alcoholic probands (Cahalan). The prevelance in the male relatives of white male and female probands is 36% and 32%; and the prevalence in their female relatives is 6.4% and 6.7%, respectively. In order to ascertain whether the great preponderance of males is due to transmissible factors, estimates of the correlation between males and between females are computed separately. Among whites, the correlation between males (male probands and male relatives) is 0.53 _+0.05 and between females is 0.08 _C 0.10, a significant difference. The hypothesis that the difference is due to transmitted factors is tested by hypothesizing that it is not transmitted. The multifactorial model is then used to predict the correlation between probands and relatives of the opposite sex from the
93
correlations between same-sexed probands and relatives. The predicted value of the correlation between opposite-sexed relatives is 0.31 and the observed value is 0.28 t 0.06. This finding strongly suggests that alcoholism in males and alcoholism in females does not run in different families. The decreased correlation between female probands and relatives (as compared to males) is equal to that expected from the smaller proportion of affected females in the general population. With respect to the presence or absence of alcoholism, the genotypes of male and female alcoholics do not differ since they are equally able to transmit the disorder. The phenotypes of male and female alcoholics are different. Since the phenotype consists of both genotypic and environmental elements, environmental factors (e.g., exposure to heavy drinking) are sufficient to explain the difference in the prevalence of alcoholism in males and females. Furthermore, these environmental factors are not familial. Analysis of data obtained from black families leads to a similar conclusion. The multifactorial model of disease transmission appears to be a powerful device for the analyses of population and family data without requiring genetic assumptions which have led to such acrimony in the past. With respect to alcoholism, our results show that (1) among black or white populations alcoholism is familial to a large degree; (2) alcoholism in males and alcoholism in females is not transmitted independently; and (3) in spite of the phenotypic difference between male and female alcoholism (as shown by the different population prevalences), the genotypes of male and female alcoholics do not differ. This suggests that the large sex effect in this disorder can be explained by environmental sources of variation.