Rune Cederlöf

Mortality in Twins in Relation to Smoking Habits and Alcohol Problems

Results are presented from an 11-year study on 9,000 pairs. On a nonpair basis, a significant hypermortality was related to smoking in men and women. Among 706 male dizygotic smoking-discordant pairs born 1901 to 1925, 55 deaths or “first deaths” occurred in a high smoking group, against 31 in a low smoking group. Among 246 corresponding monozygotic male pairs, the numbers were 18 vs 18. For women, the numbers were 42 vs 31 among 781 dizygotic pairs, and 14 vs 13 among 326 monozygotic pairs. The hypermortality was mainly due to coronary heart disease, lung cancer, suicides, and accidents. Nonsmokers were registered at 10% in a nationwide “alcohol registry” as against 30% for high smokers. The mortality among the registered subjects was significantly higher than among the nonregistered, regardless of smoking. Data imply that part of the hypermortality among smokers is not due to smoking per se, but to factors associated with smoking.

A twin methodology for the study of genetic and environmental control of variation in human smoking behavior.

A method is presented for partitioning the variance associated with human smoking behavior into additive genetic, nonadditive genetic, prenatal environmental, postnatal familial environmental, and postnatal extrafamilial environmental components. Estimations can also be made of additive genetic and residual correlations between spouses and of the correlation between parental additive genetic effect and progeny nonadditive genetic and environmental effect. The variance estimates are free of the biases that might result from these correlations. The statistical genetic analysis is being applied to a large group of MZ and DZ twins, their spouses, and their adult children who live in southern Sweden. Blood samples from each subject will be used to identify their genetic constitution for a number of biochemical polymorphisms, some of which may be considered a priori to have possible relationships to smoking. Associations and genetic linkages between biochemical marker loci and quantitative behavioral traits will be sought. Traits of interest include a wide array of tobacco-use variables, motives for smoking, personality and cognitive variables, and other variables associated with drug use and health. Zygosity determinations based on biochemical polymorphisms have indicated MZ to DZ and DZ to MZ misclassification rates of 0% and 6.15%, respectively, when based solely on external morphology and questionnaire data. The nonpaternity ratio of the fathers with respect to their supposedly biological children is estimated to be 0.28%. Gene frequency estimates for 21 marker loci show that the sample of twins and their relatives is quite representative of the Swedish population at large. All loci were in Hardy-Weinberg-Castle equilibrium, with no evidence of assortative mating for biochemical traits. The MZ twins are significantly more concordant than the DZ twins with respect to whether they have ever had a smoking habit.

Mortality in smoking discordant monozygotic and dizygotic twins. A study on the Swedish Twin Registry.

Among 706 male, dizygotic, smoking discordant twin pairs born in 1901 to 1925, 13 deaths occurred among nonsmokers or less exposed partners against 34 among smokers or more exposed. In 246 corresponding monozygotic pairs the figures were 14 against 9. The excess mortality among male dizygotic smokers was not associated with any specific cause of death. Four cases of lung cancer among males occurred only in smokers. Accidents and suicides seemed to be associated with smoking, supporting the hypotheses regarding differences in personality typebetween smokers and nonsmokers. Only time will show whether trends found are stable. The data suggest, however, that part of the greater mortality in smokers is not due to smoking per se but to factors associated with smoking.

Respiratory symptoms in twins: effects of residence-associated air pollution, tobacco and alcohol use, and other factors.

The relationship of chronic respiratory symptoms and residence-associated air pollution was evaluated through use of questionnaire data on twins in the National Research Council Twin Registry. Estimates of air pollution were based on residential and work place history. Two different scores were developed. One score evaluated residence only in terms of an urban-rural continuum and the other provided quantitative estimates of air pollution in postal Zone Improvement Program locations. Among individuals, respiratory symptoms were found to be related to urban residence as measured by the first score, but not to the more specific measure of air pollution exposure. Smoking, the drinking of alcohol and socioeconomic status were also positively associated with respiratory symptoms. No significant differences were noted between members of twin pairs if one twin maintained a more urban residence than the other or if one twin had a higher measure of exposure to air pollution than the other. The latter comparisons us...

The Validity of the Questionnaire Diagnosis

Validation of a mailed questionnaire concerning angina pectoris has been performed using 69 male twins with the diagnosis “angina pectoris” according to the questionnaire. Of these, 22% could be verified at the clinical examination. If all clinically suspected cases were included together with the cases with a pathological electrocardiogram the confirmation rate was 57%. The confirmation rate was higher, but not significantly so, if the criteria for angina pectoris were altered so that only those with central chest pain were included. The frequency of pathological ECGs in cases with a clinical diagnosis of angina pectoris was significantly higher than in those with a questionnaire diagnosis, which indicates that the validity of the clinical diagnosis is greater. The results indicate that the questionnaire is very useful for screening cases with coronary heart disease. If it is used at prevalence studies or effect studies, one has to be aware of the relatively high frequency of false-positives.

The Swedish twin registry--past and future use.

The Swedish Twin Registry of the Karolinska Institute comprises about 10 000 sets of twins, and was built up in 1961-1962. It covers about 95% of all Swedish same-sexed twins that were born in the country in 1886-192 5 and were still living as unbroken pairs at the time of compilation. The compilation procedure has been presented in detail by Cederlof (1966 a ), and will be summarized as follows. Since the middle of the last century, a rather unique system for population registration has existed in Sweden. It is based not only on birth records, but also on migration records. As soon as an individual moves away from the place he lives, he has to notify the authorities as to where he moves. This system made it possible for us to follow-up any individual from his place of birth to his next place of living, and so on, until we found his current address or had to discard him as deceased. We started, in that way, with about 41 000 multiple birth records, handscreened from about 3½ million birth records from all Sweden during the period in question, and ended with a series of about 12 000 located sets of twins. Of the remainder, about 26 000 had to be discarded, due to death of one or both partners; 1 000, due to emigration to foreign countries; and 100, due to hospitalization in mental asylums, or home for aged people, etc. In the compilation procedure we lost track of about 1 100 individuals, or 1.5%. The zygosity of the twins has been determined with the aid of some similarity questions contained in a questionnaire, mailed to all the twins in the registry. Out of several questions, one proved to be of high reliability, namely the very simple question whether the twins as children were as alike as two peas in a pod, or of family likeness only. We assumed that if both twins in a set agreed in saying that they had been as alike as two peas in a pod, the pair was MZ. If they, on the other hand, agreed in saying that they had been of family likeness only, we regarded the pair as DZ. We validated this questionnaire diagnosis by analyzing the outcome from a subsample of 200 pairs who had also been examined serologically in regard to five markers, A 1 A 2 BO, MN, Rh, Hp, and Gm. The results were reported here in Rome in 1961 and showed an agreement in diagnoses of 95% for MZ and 90% for DZ (Cederlof et al, 1061).

On the Determination of Odor Thresholds in Air Pollution Control—An Experimental Field Study on Flue Gases from Sulfate Cellulose Plants

From the hygienic point of view, not only the health hazards caused by air pollutants but also the odor from emitted flue gases should be reduced to a minimum. An effective control of the risk of odor at ground level presupposes knowledge of the source concentration of the odoriferous gas as well as its odor threshold. This threshold has to be estimated empirically, as the flue gases often contain a complex mixture of different odoriferous substances, the odor thresholds of which are in most cases unknown. For this purpose a method has been developed for estimating the odor thresholds of flue gases emitted, from different industrial processes. The method, afield method, is based on an exposure procedure, a number of subjects compare different concentrations of the flue gas with samples of fresh air and decide at what concentration the flue gas is no longer noticeable. The gas samples used are neither compressed, nor absorbed or heated before the exposure test. The method has been used in two studies on ga...

The Cotwin Method and Experimental Science

A strict evaluation of cause and effect has for long been regarded to require the tools of experimental design. The main approach is to constitute two or more subject groups by randomization or equating procedures, whereupon one or more groups will be manipulated by the experimenter, whilst one groups is left unmanipulated and thus serves as a control group. There are numerous experimental designs aimed at quantifying the effect of manipulation, one of which is the cotwin control method. The advantage of the method is the minimizing of the intrapair variance by the genetic identity between the members of a pair. Experiments, however, have limitations in problems where the presumed causal factor cannot be manipulated but exists in certain population groups and not in others. In comparing such groups the method of randomization in its true sense cannot be employed. Even matching or equating may cause bias because the variable or variables which induced the presumed causal factor in certain individuals may not be known or measurable and are thus not equatable. In such cases a modified cotwin method may be used, which employs twins where the one member has the presumed causal factor and his cotwin not. The results of a comparison between the members of such discordant pairs will not be biased by genetic differences that may be correlated to the presumed causal factor. The greater resemblance between the twins in a pair in early environmental influences will further enhance the reliability of the method. This application of the cotwin method is of great value in epidemiological research in connection with evaluation of the effect of environmental exposures such as air pollution, tobacco smoking, etc. It has been applied in this sense in Denmark, USA, and Sweden, and examples will be given.