Bernice H. Cohen

Effects of pulmonary function on mortality

Survivorship data from a 24 year longitudinal study of 874 male volunteers in the Baltimore Longitudinal Study of Aging were used to assess the role of pulmonary function on total mortality. Even when age and smoking were considered, the ratio of forced expiratory volume in 1 sec to its predicted value was significantly associated with mortality from all causes. Individuals with poorer pulmonary function showed greater mortality during the follow-up period of this study. This relationship was also seen among never smokers in this sample, further supporting the hypothesis that impaired pulmonary function is itself a predictor of total mortality and may contribute to a number of disease processes.

Genetic and environmental effects on the development of myopia in Chinese twin children

In order to assess the relative and interactive importance of genetic and environmental components on the development of myopia in Chinese school children aged from 10 to 15 years, a population-based sample of 361 same-sexed twin pairs recruited through stratified cluster sampling was studied. Zygosity of twin pairs was determined by Mendelian traits, red cell antigen systems, and continuous dermatoglyphic characteristics; while myopia was diagnosed by both objective and subjective techniques. Studying and reading habit was obtained from cotwins and their parents through a life style questionnaire. Age-sex-adjusted concordance rate derived from multiple regression equation was used in the analysis. Conventional comparison of intrapair concordance between monozygotic (MZ) and dizygotic (DZ) twins was used to assess the importance of a genetic component in the determining of myopia, and a significant genetic influence was observed. Environmental influence on myopia was evaluated through MZ cotwin method, and MZ cotwins with concordant studying and reading habits were significantly more concordant in myopia than those MZ cotwins with discordant habits. The possible effect of gene-environment interaction on myopia was explored, and concordance in myopia was found significantly associated with the interaction between zygosity and habit of studying and reading. These observations suggested that the impact of the environmental factor on the development of myopia may be influenced by genotype, and vice versa.

Major genetic mechanisms in pulmonary function.

Regressive models were used to search for possible major gene effects on pulmonary function in two groups of families: one ascertained through patients with chronic obstructive pulmonary disease [COPD defined as forced expiratory volume in one second (FEV1) less than 70% forced vital capacity (FVC)] and the other ascertained through patients with non-pulmonary disorders. There were 85 COPD families with data on 270 individuals and 56 non-pulmonary families with data on 199 individuals. The analysis was done on residuals obtained from a regression of FEV1 on age, sex, race, height, and ascertainment group. Smoking status was incorporated directly as a covariate in the regressive models. Data on probands were excluded in this analysis as a partial correction for ascertainment bias. The best fitting model for the 85 COPD families included a major gene effect with sex specific variances, but no residual familial correlation. The best fitting model for the non-pulmonary families was one with no major gene effect and no residual familial correlation. Cigarette smoking was a significant covariate in both groups of families. Testing for heterogeneity showed a significant difference in the control of pulmonary function among these COPD and non-pulmonary families (X2 = 20.12 on 6 df; p = 0.0026). Major gene effects appear to be limited to these COPD families, while there was no evidence for major gene effects in the non-pulmonary families.

Genetic heterogeneity of prematurity and intrauterine growth of retardation: Clues from the Old Order Amish

We studied differences in the role of genetic factors in prematurity and intrauterine growth retardation with the use of data on 312 Amish singleton live children ascertained from Amish records in Lancaster county, Pennsylvania, between 1969 and 1980. Birth and death certificates were obtained on all children, and inbreeding coefficients of child, mother, and father were computed by use of the path method of tracing common ancestors in a unique genealogic registry of Amish ancestors dating back to the 1700s. Multivariate analysis with linear and log linear models showed that a lower mean gestational age and a higher risk of prematurity (less than 37 weeks) and borderline maturity (37 to 38 weeks) were significantly associated with increased maternal inbreeding but not child or paternal inbreeding. On the other hand, a higher risk of intrauterine growth retardation (less than the tenth percentile in birth weight for gestational age) and mild intrauterine growth delay (tenth to twenty-fifth percentile) were associated with increased child inbreeding but not maternal or paternal inbreeding. The analysis suggests the presence of genetic heterogeneity in the etiology of prematurity and intrauterine growth retardation; while prematurity is mostly related to the maternal genotype, intrauterine growth retardation is related to the fetal genotype. The study reemphasizes the need for separating low birth weight into prematurity and intrauterine growth retardation in genetic and epidemiologic studies.

Reproductive and marital experience of parents of children with Down's syndrome (mongolism)+

An epidemiologic study of the parents and siblings of 216 children with Downs syndrome and of 216 control children matched on the basis of maternal age at the time of the childs birth demonstrated no differences in the frequencies of abortions, stillbirths, or congenital abnormalities, nor did the siblings of the children with Downs syndrome have a higher frequency of deaths from acquired causes than did the siblings of the controls. Mothers in the two groups were similar in fertility and there were no differences in their menstrual histories. A significantly higher frequency of multiple marriages prior to the birth of the index child was observed in the mothers of the affected children. Some possible interpretations of these observations are discussed.

Parental age in Down's syndrome (mongolism)****

Because of the new insight afforded by recent cytogenetic discoveries, the need for further clarification of the parental age effect in Downs syndrome was apparent. As part of an epidemiologic study of Downs syndrome in Baltimore, Maryland, the relative significance of maternal and paternal ages as etiological factors was evaluated. By comparing a control group matched by birth certificates, parental age was studied directly, first by controlling maternal, and then paternal ages. There was no statistically significant association between paternal age and Downs syndrome, but the reltionship between Downs syndrome and increased maternal age remains unequivocal. Other observations are made about parental age in Downs syndrome and other trisomic conditions.

THE EPIDEMIOLOGICAL STUDY OF MONGOLISM IN BALTIMORE

The epidemioiogical study of mongolism in Baltimore was initiated primarily to determine whether there was a relationship between parental exposure to ionizing radiation and the occurrence of mongolism among offspring. The principal stimuli for this inquiry were the known relationship between ionizing radiation and chromosomal aberrations, the association of leukemia and mongolism, and the leukemogenic effect of radiation. In addition to collecting data for this major objective, information was obtained and analyzed concerning other factors, such as parental age and maternal reproductive patterns, which might be associated with chromosomal aberrations. In this report, we shall summarize the study results and briefly describe the procedures of a supplementary investigation undertaken this year and currently in progress.

INBREEDING AND PREREPRODUCTIVE MORTALITY IN THE OLD ORDER AMISH. II. GENEALOGIC EPIDEMIOLOGY OF PREREPRODUCTIVE MORTALITY

The effects of offspring and parental inbreeding on prereproductive mortality (death before age 20 years) in the historical population of the Lancaster County, Pennsylvania, Old Order Amish were investigated using the Amish genealogic registry, which contains information on 42,465 births dating to the time of the pioneer migrants in the 1700s. Inbreeding coefficients for offspring and parents were computed using the path method of tracing common ancestors in the multigenerational pedigrees. In this population, prereproductive mortality declined from about 15% in the late 1800s to about 5% after 1930. Offspring inbreeding was found to be an independent predictor of prereproductive mortality after multivariate adjustment for demographic risk factors for mortality. Moreover, the higher the coefficient, the higher the relative risk of prereproductive death, and the higher the risk of multiple deaths in the same sibship. There was no evidence of declining inbreeding effects over 10 generations of continuous inbreeding, nor of any significant parental inbreeding effects. Because of the high levels of inbreeding, it could be shown that inbreeding accounts for about 40% of all prereproductive deaths in the present population. Genetic load analysis showed an average of about 1.7 lethal equivalents and a mostly mutational load.

MILK DRINKING AND POSSIBLE PROTECTION OF THE RESPIRATORY EPITHELIUM

In the Hopkins investigation, detailed interviews as well as spirometry were obtained on 2539 non-patient adult participants. The interviews included questions regarding smoking habits, family history, socioeconomic status, respiratory symptoms, certain dietary factors and beverage consumption. For the analyses of risk factors, all patients were excluded from the original study population, which consisted not only of several groups of patients along with their relatives, but also neighborhood controls. teachers, and other groups. Thus, only those subjects over 20 years of age who were not ascertained on the basis of their own health status were considered. CB was identified by the report of cough and phlegm production for three or more months per year for two consecutive years. In this population, a significantly lower prevalence of CB was found among study subjects who drank milk. CB was found in 17.7% of 351 individuals who did not drink milk, but in only 11.7% of 1196 adults who drank milk daily (p < 0.01). This significant difference persisted after binary multiple regression adjustment for cigarette smoking, one-second forced expiratory volume and other potentially confounding variables: age, sex, race, socio-economic status, education, alcohol and coffee intake [9]. However, milk drinking was not associated with a reduction in CB prevalence among those who had never been smokers. Of nonsmoking adults who were not milk drinkers, 6.0% had CB, not significantly different from the CB prevalence of daily milk drinkers (6.7%). In contrast,

Estimating familial aggregation while adjusting for covariates Application to pulmonary function data from black and white sibships

Although crude correlations are useful in family studies, some adjustment for effects of risk factors that vary both within and among families if often needed. A linear model for estimating sibship correlations while simultaneously considering height, age, race, sex, ascertainment, and smoking status was used on pulmonary function data on 1-second forced expiratory volume (FEV1) and the natural logarithm of the ratio of FEV1 to forced vital capacity (lnFEV%) from 402 adults in 152 white sibships and 172 adults in 59 black sibships. Crude correlations of .271 +/- .048 (FEV1) and .342 +/- .047 (lnFEV%) decreased significantly to .206 +/- .048 and .231 +/- .048, respectively, after adjustment. For black and white sibs, adjusted intraclass correlations, although not statistically different, were .153 +/- .089 and .225 +/- .055 (FEV1), respectively, and were .103 +/- .088 and .275 +/- .054 (lnFEV%), respectively, suggesting that pulmonary function may aggregate more strongly among whites. This analysis illustrates how risk factor adjustment can be readily incorporated into familial correlation studies.