Grandsons of Alcoholics A Test of Sex-Linked Transmission of Alcohol Abuse Lennart
Kaij, MD,
Jan
Dock,
ML
test the hypothesis of a sex-linked factor influencing the of alcoholism and alcohol abuse, alcoholism or abuse rates were compared for 136 sons of the sons vs 134 sons of the daughters of 75 alcoholics. No substantial difference between the groups of grandsons was found in frequency of officially registered alcoholism or alcohol abuse, or both, which suggests no sex-linked factor is involved. The total sample was also used to calculate the risk of such registration for the grandsons; the rate of registration by the grandsons' fifth decade of life was 43%, approximately three times that of the general male population, and even higher than the equivalent rate in brothers of alcoholics. This result is incompatible with an assumption of a recessive gene being involved in the occurrence of alcoholism, though it fits with the assumption of a dominant gene. (Arch Gen Psychiatry 32:1379-1381, 1975) \s=b\ To
occurrence
Alcoholism and alcohol abuse
are
about 5 to 30 times
jnL as common in men as in women. From a genetic viewpoint, this raises the suspicion that the occurrence is influenced by a sex-linked factor, ie, a gene or genes lo¬
cated in the X chromosome. The first substantial support of this suspicion was pro¬ vided by Cruz-Coke's1·2 finding of an association between alcoholic cirrhosis of the liver and color blindness, and, later, between alcohol addiction and color blindness.34 These findings have been refuted both on empirical and theoretical grounds. Thus, other studies have failed to confirm the associa¬ tion between alcoholism and color blindness,57 still oth¬ ers810 have shown that the excess of color-blind men among alcoholics with cirrhosis is due to a transient, prob¬ ably toxic, effect of alcohol. Recently, new data have par¬ tially supported the original finding11 and the matter can¬ not yet be regarded as settled. Accepted
for publication Nov 7, 1974. From the Department of Psychiatry, University of Lund, Malm\l=o"\, Sweden. Reprint requests to the Psykiatriska Kliniken, Lunds Universitet, Malm\l=o"\ Allm\l=a"\nnaSjukhus, 214 01 Malm\l=o"\,Sweden (Dr Kaij).
Winokur12 rejected the hypothesis of sex linkage based evidence provided by calculations of the sex ratio of al¬ coholic sibs of alcoholics in Amark's13 samples. A more di¬ rect way of testing the sex linkage of alcoholism is, of course, to study the second generation offspring of alcohol¬ ics.14 The present report gives the preliminary findings of such a study. The hypothesis tested was that those grand¬ children of an alcoholic man who carry his X chromosome, ie, the sons of his daughters, will show a higher frequency of alcohol addiction and alcoholism than those who carry his Y chromosome, ie, the sons of his sons. on
METHODS The study was carried out in Malmö, Sweden's third largest city with 250,000 inhabitants. From a local register of persons with so¬ cial complications of alcohol abuse (ranging from a single convic¬ tion for drunkenness to severe social decline) were chosen index subjects fulfilling the following criteria: (1) married men born in 1889 or earlier (2) who were addicted to alcohol and (3) as a conse¬ quence had been either a danger to themselves or others, or inca¬ pable of running their own lives or severely disturbing to others, and (4) had been subjected to compulsory supervision by the au¬ thorities or care in a home for alcoholics. The index subjects should be old enough to have as many grand¬ children above 15 years of age as possible. On the other hand, they must not be too old to have had a chance of entering the register, which was started in the 1920s. The last three criteria are quoted from the Swedish law regarding care of alcoholics. (For details see
Amark.13) Seventy-five men born within the years from 1870 to 1887 were found to fulfill the criteria. As most of them, due to their ages, had not been subjected to social intervention since the 1930s or early 1940s when medical examination of this clientele was minimal, there are few psychiatric descriptions. Those that exist leave no doubt, however, that the subjects were alcoholics also by medical
criteria.'3 The index subjects were followed up through the population register at every parish where they had lived from birth to either death or present place of residence. All children for whom they were legal fathers were recorded during this procedure and the children were followed up in the same way. The grandchildren were thus recorded and also followed up, al-
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1.—Frequency of Grandsons of Alcoholics Registered for Any Kind of Alcohol Abuse
Table 3.—Number of Sibships in Third Generation With at Least One Registered Male Member
Table Ages
Sons of Sons
in
1973,*
Regis-
yr 55-45 44-35 34-25 24-15
6 42 61 27 136
t
Total
Regis-
Regis-
tered Pt tered N tered 2 .3333 8 4 6 .5000 14 .4286 11 .3798 34 8 .2353 76 19 .2500 13 .2131 71 8 .1127 132 21 .1591 .1250 2 .0741 21 4 .1905 48 6 52 28 .2059 134 24 .1791 270 .1926
30.7 ±3.6
Sons With Sons
84 22 .2619
81 18 .2222
Or age at death.
signifies proportion.
Ages in 1973, yr 55-45 44-35 34-25 24-15 Total
Severe
signifies proportion.
31.5 ±3.9
Table 2.—Distribution of Registered Grandsons per Severity of Alcohol Abuse*
*
Daughters With Sons
Registered
Table
Mean age, yr *
Sons of Daughters
,-«-..-«-...-.—
.-»-
1 4 3
5 5
2 5
11 13
8
10
10
28
cases
indicated
Ages in
Observed
Proportion
Expected Proportion
Differ¬
1973, yr 55-45 44-35 34-25 24-15
.4286 .2500 .1591 .1250 .1926
.1441 .1392 .1147 .0652 .1145
.2845 .1108 .0444 .0548
Sons of Daughters
sons of Sons ,-.-,
4.—Frequencies of Registration Among Grandsons of Alcoholics and General Population
3
12
9
24
by 1 ; moderate, 2; and mild, 3.
P* .0082 .0045 .071 .084
ence
Binomial test.
Cumulated age-specific risk of entering register in the sample (o-o) and the general population (x-x).
Frequency
though only grandsons born in 1958 or earlier were included, since
the granddaughters are of little relevance to the main hypothesis and the younger children's risk for alcoholism is as yet too small to warrant the investment of time and work. A total of 352 children and 270 grandsons older than 15 years of age was ascertained. At the time of the investigation ten grand¬ sons were dead, five sons of daughters and five sons of sons of the index subjects. As the first step in the investigation of the sample, the national register of persons with a record of social intervention for alcohol abuse was consulted, and the registered grandsons were recorded.
.50
.40
RESULTS The results
are
summarized in Table 1. There
were
equally as many sons of the index subjects' sons as of their daughters. The mean age of the sons of the daughters was slightly higher than that of the sons of the sons. The fre¬ quencies of registered persons were equally distributed in the two groups, and the differences of frequencies within the age groups were statistically insignificant. The main hypothesis must be rejected. An attempt was made to differentiate between degrees of severity of alcohol abuse as reflected in the register (Table 2). Group 1 includes those who have been under compulsory treatment, most probably chronic alcoholics also in a medical sense. Group 3 includes those who have but a single notation in their records and group 2 the re¬ maining men with notations. There were 2.65 times as many sons of sons as there were sons of daughters in the group with most
severe
.30
.20
.10
abuse but the difference is not sta¬
tistically significant. Furthermore, it goes against the hypothesis. As one of the F, sibships (grandchildren) included six and another four registered brothers, the number of sib-
J. Age,
yr
10
Downloaded From: https://jamanetwork.com/ by a University of Massachusetts Amherst User on 12/22/2019
20
30
40
50
60
ships with at least one registered brother produced by daughters and sons of the index men were compared (Table 3). There was no significant difference in the num¬ ber of affected sibships born to daughters vs those born to
30% of
sons
of the F2 generation (grandchildren), but is very un¬ likely to affect the sons of the daughters of the index sub¬ jects, as the children were recorded from the population registers where the birth certificates are sent. However, the bias would not affect the result of the study, were the main hypothesis true, as it is the X chromosomes from the grandfather, ie, those passed by his daughters, that count; while the sons of the sons, assuming nonassortive matings, receive no more affected X chromosomes than does the general population. The results indicate a threefold risk through the fifth decade of life for grandchildren of alcoholics to be regis¬ tered for alcohol abuse at least once. The risk is even slightly higher than that for brothers of alcoholics.13 This result is incompatible with an assumption of a recessive gene being of decisive importance in the transmission of alcohol abuse and alcoholism as defined here. On the other hand, it is compatible with an assumption of a dominant
of the index men. The sample was also used for a gross estimate of the risk of grandsons of alcoholics for entering the official reg¬ ister as compared with the general population of men (Table 4, Figure). The age-specific prevalence risks in the general male population were calculated from a census of men born in 1917 and followed up through 1964.16 In the oldest age group, which has passed most of the risk age, the frequency of registered grandsons is 43%, which is 2.97 times the risk of the population, a highly significant dif¬ ference. The shapes of the curves of the cumulated risks also indicate that the investigated sample is of a different character from the population in general. COMMENT In the scientific study of alcoholism, the question of def¬ inition is difficult but crucial. The definition used in the present study is a social one, and, more specifically, based on the social consequences of alcohol abuse, expressed as having entered official registers. This definition is unsatis¬ factory for many scientific purposes14 but in the present context the only possible one for finding the index sub¬ jects. As a measure of the status of the grandchildren, it is unsatisfactory but can be used provisionally. The ratio¬ nale is that a notation in the register, even of a single con¬ viction for drunkenness, is highly correlated to alcoholism and alcohol abuse as defined in other ways, eg, medically. Thus, in a sample of twins,15 those who were registered were five times as often diagnosed as alcoholic as those who were not. The association between being registered and the degree of drinking habits was highly significant ( 2 88.89, df=4, C coefficient .468). In Ämark's13 sample of alcoholics treated in a mental hospital, 56% appeared in the register, as compared with 12.4% in the corresponding male population. Thus, registration may be seen as an in¬ dication of the frequency of alcoholism in the sample. A sample of alcohol abusers selected by social criteria is certainly a biased one, as compared with a sample based on medical criteria.1317 Low social class, criminality, and psychoses are probably those variables most overrepresented. Therefore, no general conclusion regarding alcohol abusers and alcoholics in general can be drawn. On the other hand, the same measure was applied for both the index subjects and the grandchildren and it seems im¬ probable that the bias should affect sons of sons and sons of daughters differently. The results therefore are true for this particular population. A third limitation of the technique, which the present study has in common with most family studies, is the "pa¬ ter semper incertus" issue. In a recent study in England, =
=
legal children could
not be biological children ac¬ to blood studies.18 In the present study, such cording group a bias would affect both sons and daughters of the F, gen¬ eration (children) to the same extent and the sons of the sons
gene.
The assumption of a sex-linked gene cannot be upheld in the light of the present study, neither for the main measurement nor for the severe forms of social conse¬ quences of alcohol abuse. References 1. Cruz-Coke R: Colour-blindness and cirrhosis of the liver. Lancet
2:1064-1065, 1964.
2. Cruz-Coke R: Colour-blindness and cirrhosis of the liver. Lancet
1:1131-1133, 1965. 3. Cruz-Coke R, Varela A: Colour-blindness and alcohol addiction. Lancet 2:1348, 1965. 4. Cruz-Coke R, Varela A: Inheritance of alcoholism: Its association with colour-blindness. Lancet 2:1282-1284, 1966. 5. Gorrel GJ: Inheritance of alcoholism. Lancet 1:274, 1967. 6. Thuline HC: Inheritance of alcoholism. Lancet 1:274-275, 1967. 7. Dittrich H, Neubauer 0: St\l=o"\rungendes Farbsehens bei Leberkrankheiten. Munch Med Wochenschr 109:2690-2693, 1967. 8. Fialkow PJ, Thuline HC, Fenster LF: Lack of association between cirrhosis and the common types of color blindness. N Engl J Med 275:584-587,
1966. 9. Smith JW, Brinton GA: Color-vision defects in alcoholism. Q J Stud Alcohol 32:41-44, 1971. 10. Smith JW: Color vision in alcoholics. Ann NY Acad Sci 197:143-147, 1972. 11. Mardones J: Evidence of genetic factors in the appetite for alcohol and alcoholism. Ann NY Acad Sci 197:138-142, 1972. 12. Winokur G: X-borne recessive genes in alcoholism. Lancet 2:466,1967. 13. \l=A%o\markC: A study in alcoholism. Acta Psychiatr Neurol Scand, suppl 70, 1951. 14. Kaij L: Definitions of alcoholism and genetic research. Ann NY Acad Sci 197:110-113, 1972. 15. Kaij L: Alcoholism in Twins. Stockholm, Almqvist & Wiksell, 1960. 16. Cure or Fines. Swedish government publication, 1968, p 56. 17. Kaij L: Biases in a Swedish social register of alcoholics. Soc Psychol 5:216-218, 1970. 18. Philipp EE: Discussion: Moral, social and ethical issues, in Law and Ethics of AID and Embryo Transfer. Amsterdam, Ciba foundation symposium 17, new series, 1973, p 63.
Downloaded From: https://jamanetwork.com/ by a University of Massachusetts Amherst User on 12/22/2019
Kaij, MD,
Jan
Dock,
ML
test the hypothesis of a sex-linked factor influencing the of alcoholism and alcohol abuse, alcoholism or abuse rates were compared for 136 sons of the sons vs 134 sons of the daughters of 75 alcoholics. No substantial difference between the groups of grandsons was found in frequency of officially registered alcoholism or alcohol abuse, or both, which suggests no sex-linked factor is involved. The total sample was also used to calculate the risk of such registration for the grandsons; the rate of registration by the grandsons' fifth decade of life was 43%, approximately three times that of the general male population, and even higher than the equivalent rate in brothers of alcoholics. This result is incompatible with an assumption of a recessive gene being involved in the occurrence of alcoholism, though it fits with the assumption of a dominant gene. (Arch Gen Psychiatry 32:1379-1381, 1975) \s=b\ To
occurrence
Alcoholism and alcohol abuse
are
about 5 to 30 times
jnL as common in men as in women. From a genetic viewpoint, this raises the suspicion that the occurrence is influenced by a sex-linked factor, ie, a gene or genes lo¬
cated in the X chromosome. The first substantial support of this suspicion was pro¬ vided by Cruz-Coke's1·2 finding of an association between alcoholic cirrhosis of the liver and color blindness, and, later, between alcohol addiction and color blindness.34 These findings have been refuted both on empirical and theoretical grounds. Thus, other studies have failed to confirm the associa¬ tion between alcoholism and color blindness,57 still oth¬ ers810 have shown that the excess of color-blind men among alcoholics with cirrhosis is due to a transient, prob¬ ably toxic, effect of alcohol. Recently, new data have par¬ tially supported the original finding11 and the matter can¬ not yet be regarded as settled. Accepted
for publication Nov 7, 1974. From the Department of Psychiatry, University of Lund, Malm\l=o"\, Sweden. Reprint requests to the Psykiatriska Kliniken, Lunds Universitet, Malm\l=o"\ Allm\l=a"\nnaSjukhus, 214 01 Malm\l=o"\,Sweden (Dr Kaij).
Winokur12 rejected the hypothesis of sex linkage based evidence provided by calculations of the sex ratio of al¬ coholic sibs of alcoholics in Amark's13 samples. A more di¬ rect way of testing the sex linkage of alcoholism is, of course, to study the second generation offspring of alcohol¬ ics.14 The present report gives the preliminary findings of such a study. The hypothesis tested was that those grand¬ children of an alcoholic man who carry his X chromosome, ie, the sons of his daughters, will show a higher frequency of alcohol addiction and alcoholism than those who carry his Y chromosome, ie, the sons of his sons. on
METHODS The study was carried out in Malmö, Sweden's third largest city with 250,000 inhabitants. From a local register of persons with so¬ cial complications of alcohol abuse (ranging from a single convic¬ tion for drunkenness to severe social decline) were chosen index subjects fulfilling the following criteria: (1) married men born in 1889 or earlier (2) who were addicted to alcohol and (3) as a conse¬ quence had been either a danger to themselves or others, or inca¬ pable of running their own lives or severely disturbing to others, and (4) had been subjected to compulsory supervision by the au¬ thorities or care in a home for alcoholics. The index subjects should be old enough to have as many grand¬ children above 15 years of age as possible. On the other hand, they must not be too old to have had a chance of entering the register, which was started in the 1920s. The last three criteria are quoted from the Swedish law regarding care of alcoholics. (For details see
Amark.13) Seventy-five men born within the years from 1870 to 1887 were found to fulfill the criteria. As most of them, due to their ages, had not been subjected to social intervention since the 1930s or early 1940s when medical examination of this clientele was minimal, there are few psychiatric descriptions. Those that exist leave no doubt, however, that the subjects were alcoholics also by medical
criteria.'3 The index subjects were followed up through the population register at every parish where they had lived from birth to either death or present place of residence. All children for whom they were legal fathers were recorded during this procedure and the children were followed up in the same way. The grandchildren were thus recorded and also followed up, al-
Downloaded From: https://jamanetwork.com/ by a University of Massachusetts Amherst User on 12/22/2019
1.—Frequency of Grandsons of Alcoholics Registered for Any Kind of Alcohol Abuse
Table 3.—Number of Sibships in Third Generation With at Least One Registered Male Member
Table Ages
Sons of Sons
in
1973,*
Regis-
yr 55-45 44-35 34-25 24-15
6 42 61 27 136
t
Total
Regis-
Regis-
tered Pt tered N tered 2 .3333 8 4 6 .5000 14 .4286 11 .3798 34 8 .2353 76 19 .2500 13 .2131 71 8 .1127 132 21 .1591 .1250 2 .0741 21 4 .1905 48 6 52 28 .2059 134 24 .1791 270 .1926
30.7 ±3.6
Sons With Sons
84 22 .2619
81 18 .2222
Or age at death.
signifies proportion.
Ages in 1973, yr 55-45 44-35 34-25 24-15 Total
Severe
signifies proportion.
31.5 ±3.9
Table 2.—Distribution of Registered Grandsons per Severity of Alcohol Abuse*
*
Daughters With Sons
Registered
Table
Mean age, yr *
Sons of Daughters
,-«-..-«-...-.—
.-»-
1 4 3
5 5
2 5
11 13
8
10
10
28
cases
indicated
Ages in
Observed
Proportion
Expected Proportion
Differ¬
1973, yr 55-45 44-35 34-25 24-15
.4286 .2500 .1591 .1250 .1926
.1441 .1392 .1147 .0652 .1145
.2845 .1108 .0444 .0548
Sons of Daughters
sons of Sons ,-.-,
4.—Frequencies of Registration Among Grandsons of Alcoholics and General Population
3
12
9
24
by 1 ; moderate, 2; and mild, 3.
P* .0082 .0045 .071 .084
ence
Binomial test.
Cumulated age-specific risk of entering register in the sample (o-o) and the general population (x-x).
Frequency
though only grandsons born in 1958 or earlier were included, since
the granddaughters are of little relevance to the main hypothesis and the younger children's risk for alcoholism is as yet too small to warrant the investment of time and work. A total of 352 children and 270 grandsons older than 15 years of age was ascertained. At the time of the investigation ten grand¬ sons were dead, five sons of daughters and five sons of sons of the index subjects. As the first step in the investigation of the sample, the national register of persons with a record of social intervention for alcohol abuse was consulted, and the registered grandsons were recorded.
.50
.40
RESULTS The results
are
summarized in Table 1. There
were
equally as many sons of the index subjects' sons as of their daughters. The mean age of the sons of the daughters was slightly higher than that of the sons of the sons. The fre¬ quencies of registered persons were equally distributed in the two groups, and the differences of frequencies within the age groups were statistically insignificant. The main hypothesis must be rejected. An attempt was made to differentiate between degrees of severity of alcohol abuse as reflected in the register (Table 2). Group 1 includes those who have been under compulsory treatment, most probably chronic alcoholics also in a medical sense. Group 3 includes those who have but a single notation in their records and group 2 the re¬ maining men with notations. There were 2.65 times as many sons of sons as there were sons of daughters in the group with most
severe
.30
.20
.10
abuse but the difference is not sta¬
tistically significant. Furthermore, it goes against the hypothesis. As one of the F, sibships (grandchildren) included six and another four registered brothers, the number of sib-
J. Age,
yr
10
Downloaded From: https://jamanetwork.com/ by a University of Massachusetts Amherst User on 12/22/2019
20
30
40
50
60
ships with at least one registered brother produced by daughters and sons of the index men were compared (Table 3). There was no significant difference in the num¬ ber of affected sibships born to daughters vs those born to
30% of
sons
of the F2 generation (grandchildren), but is very un¬ likely to affect the sons of the daughters of the index sub¬ jects, as the children were recorded from the population registers where the birth certificates are sent. However, the bias would not affect the result of the study, were the main hypothesis true, as it is the X chromosomes from the grandfather, ie, those passed by his daughters, that count; while the sons of the sons, assuming nonassortive matings, receive no more affected X chromosomes than does the general population. The results indicate a threefold risk through the fifth decade of life for grandchildren of alcoholics to be regis¬ tered for alcohol abuse at least once. The risk is even slightly higher than that for brothers of alcoholics.13 This result is incompatible with an assumption of a recessive gene being of decisive importance in the transmission of alcohol abuse and alcoholism as defined here. On the other hand, it is compatible with an assumption of a dominant
of the index men. The sample was also used for a gross estimate of the risk of grandsons of alcoholics for entering the official reg¬ ister as compared with the general population of men (Table 4, Figure). The age-specific prevalence risks in the general male population were calculated from a census of men born in 1917 and followed up through 1964.16 In the oldest age group, which has passed most of the risk age, the frequency of registered grandsons is 43%, which is 2.97 times the risk of the population, a highly significant dif¬ ference. The shapes of the curves of the cumulated risks also indicate that the investigated sample is of a different character from the population in general. COMMENT In the scientific study of alcoholism, the question of def¬ inition is difficult but crucial. The definition used in the present study is a social one, and, more specifically, based on the social consequences of alcohol abuse, expressed as having entered official registers. This definition is unsatis¬ factory for many scientific purposes14 but in the present context the only possible one for finding the index sub¬ jects. As a measure of the status of the grandchildren, it is unsatisfactory but can be used provisionally. The ratio¬ nale is that a notation in the register, even of a single con¬ viction for drunkenness, is highly correlated to alcoholism and alcohol abuse as defined in other ways, eg, medically. Thus, in a sample of twins,15 those who were registered were five times as often diagnosed as alcoholic as those who were not. The association between being registered and the degree of drinking habits was highly significant ( 2 88.89, df=4, C coefficient .468). In Ämark's13 sample of alcoholics treated in a mental hospital, 56% appeared in the register, as compared with 12.4% in the corresponding male population. Thus, registration may be seen as an in¬ dication of the frequency of alcoholism in the sample. A sample of alcohol abusers selected by social criteria is certainly a biased one, as compared with a sample based on medical criteria.1317 Low social class, criminality, and psychoses are probably those variables most overrepresented. Therefore, no general conclusion regarding alcohol abusers and alcoholics in general can be drawn. On the other hand, the same measure was applied for both the index subjects and the grandchildren and it seems im¬ probable that the bias should affect sons of sons and sons of daughters differently. The results therefore are true for this particular population. A third limitation of the technique, which the present study has in common with most family studies, is the "pa¬ ter semper incertus" issue. In a recent study in England, =
=
legal children could
not be biological children ac¬ to blood studies.18 In the present study, such cording group a bias would affect both sons and daughters of the F, gen¬ eration (children) to the same extent and the sons of the sons
gene.
The assumption of a sex-linked gene cannot be upheld in the light of the present study, neither for the main measurement nor for the severe forms of social conse¬ quences of alcohol abuse. References 1. Cruz-Coke R: Colour-blindness and cirrhosis of the liver. Lancet
2:1064-1065, 1964.
2. Cruz-Coke R: Colour-blindness and cirrhosis of the liver. Lancet
1:1131-1133, 1965. 3. Cruz-Coke R, Varela A: Colour-blindness and alcohol addiction. Lancet 2:1348, 1965. 4. Cruz-Coke R, Varela A: Inheritance of alcoholism: Its association with colour-blindness. Lancet 2:1282-1284, 1966. 5. Gorrel GJ: Inheritance of alcoholism. Lancet 1:274, 1967. 6. Thuline HC: Inheritance of alcoholism. Lancet 1:274-275, 1967. 7. Dittrich H, Neubauer 0: St\l=o"\rungendes Farbsehens bei Leberkrankheiten. Munch Med Wochenschr 109:2690-2693, 1967. 8. Fialkow PJ, Thuline HC, Fenster LF: Lack of association between cirrhosis and the common types of color blindness. N Engl J Med 275:584-587,
1966. 9. Smith JW, Brinton GA: Color-vision defects in alcoholism. Q J Stud Alcohol 32:41-44, 1971. 10. Smith JW: Color vision in alcoholics. Ann NY Acad Sci 197:143-147, 1972. 11. Mardones J: Evidence of genetic factors in the appetite for alcohol and alcoholism. Ann NY Acad Sci 197:138-142, 1972. 12. Winokur G: X-borne recessive genes in alcoholism. Lancet 2:466,1967. 13. \l=A%o\markC: A study in alcoholism. Acta Psychiatr Neurol Scand, suppl 70, 1951. 14. Kaij L: Definitions of alcoholism and genetic research. Ann NY Acad Sci 197:110-113, 1972. 15. Kaij L: Alcoholism in Twins. Stockholm, Almqvist & Wiksell, 1960. 16. Cure or Fines. Swedish government publication, 1968, p 56. 17. Kaij L: Biases in a Swedish social register of alcoholics. Soc Psychol 5:216-218, 1970. 18. Philipp EE: Discussion: Moral, social and ethical issues, in Law and Ethics of AID and Embryo Transfer. Amsterdam, Ciba foundation symposium 17, new series, 1973, p 63.
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