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C J MacLean

Publications and source records attributed to C J MacLean.

At least 55 records · Page 3Linked to original sources
PubMed1990

Estimating familial effects on age at onset and liability to schizophrenia. I. Results of a large sample family study.

Previous analyses of age at onset in schizophrenia, which is highly variable and appears to be influenced by familial factors, have neglected to consider either (1) the impact of censoring on correlations in age at onset in affected relatives or (2) the impact of correlated ages at onset on the relationship between age at onset in the proband and risk in relatives. In this report, using methods outlined in the companion paper [MacLean et al., Genet Epidemiol 7:419-426, 1990] we examine these questions in the large family data set of schizophrenia collected by Lindelius [Acta Psychiat Scand (Suppl) 216:1-125, 1970]. Ages at onset are positively correlated in pairs of affected relatives (parent-offspring approximately equal to siblings greater than nieces/nephews) and these correlations are substantially higher after correction for censoring. Early age at onset is associated with higher risk of illness in siblings and nieces/nephrews but not in children. These results are consistent with the hypothesis that age at onset in schizophrenia is influenced by familial factors which are probably genetic and which are mostly unrelated to factors influencing disease liability.

Adolescent↗
PubMed1990

Estimating familial effects on age at onset and liability to schizophrenia. II. Adjustment for censored data.

Genetic studies of disorders with adult onset often contain individuals who have not completed their age at risk when last observed. Without correction for such censoring, correlation in ages at onset among relatives is substantially underestimated. Moreover, without correction for the effect of correlated ages at onset, the relationship between age at onset in the proband and liability in relatives is substantially overestimated. The present paper describes methods for correcting the effects of censoring on these estimates. In a companion paper [Kendler and MacLean, Genet Epidemiol 7:409-417, 1990] these methods are applied to a large family study of schizophrenia.

Adolescent↗
PubMed1990

Potential bias due to prevalent diseases in prospective studies.

In prospective studies, subjects found to have the disease under investigation at the initial screening examination are commonly excluded from analyses. However, the possibility of bias due to prevalent conditions other than the disease of interest is usually not considered. In the present study, an algebraic development enables analysis of the effects of inclusion and exclusion of subjects with certain prevalent conditions upon risk estimates. Hypothetical data are presented for which an association between a risk factor and an incident disease could become null or even reversed after removing subjects with certain prevalent diseases. Bias appears even when the only association present is between risk factor and total disease incidence. Data from the Honolulu Heart Study also have been used to illustrate this finding, examining the association between coronary heart disease (CHD) incidence and smoking. Decisions regarding the inclusion or exclusion of subjects with prevalent diseases requires prior knowledge of alteration of usual risk factors levels by individuals with these diseases. Simply removing all subjects with prevalent diseases might on the contrary create bias. Therefore, people with prevalent diseases should be screened for potential alteration of their risk factor levels as a result of the diseases. The situation becomes still more complex when several risk factors and prevalent diseases need to be considered at the same time as it happens in multivariate analyses. Because this situation represents a bias, and not confounding or effect modification, controlling for the effect of prevalent diseases is not appropriate.

Aged↗
PubMed1989

The impact of altered fitness on the risk of illness in relatives.

Altered fitness of affected individuals can substantially influence the pattern of risk of illness in relatives. This altered risk can result from both changes in the distribution of genotypes and changes in the genotype-specific proportion affected or GSPA. This report examines the impact of altered fitness on the GSPA in relatives of affected probands, under a simple genetic model. The model assumes that illness results from a generalized single major locus and that fitness is dependent only upon phenotype. It is shown that i) in progenitors of probands (e.g., parents and grandparents), GSPA can vary widely as a function of the fitness of affected individuals; ii) the change in GSPA is equal in parents and grandparents; and iii) in non-progenitors (e.g., offspring, siblings, uncles/aunts), GSPA is independent of fitness effects. The GSPA in parents and grandparents is a function both of the relative fitness of affected individuals (F) and the penetrance (Q) that can be approximated by the simple formula: GSPA = FQ/(FQ + 1 - Q). The successful application of model-fitting methods for the detection of single gene variation to complex phenotypes that significantly alter fitness may, in certain circumstances, require the incorporation of "fitness effects" into the analytic model.

Attitude to Health↗
PubMed1989

Relative impact of smoking and reduced pulmonary function on peptic ulcer risk. A prospective study of Japanese men in Hawaii.

The aim of this study was to determine whether reduced pulmonary function is an independent risk factor for peptic ulcer. Among 5933 Japanese men studied in Hawaii, 243 developed gastric ulcers and 99 developed duodenal ulcers 20 yr after an examination completed in 1968. The examination included measurement of forced expiratory volume in 1 s and a detailed smoking history. The percent predicted forced expiratory volume was significantly and inversely related to ulcer incidence, but not after adjustment for smoking or among those who had never smoked. Cigarettes were associated with increased ulcer risk in both stomach and duodenum but showed a dose-response in pack years only for gastric ulcer. We conclude that the association of reduced pulmonary function with peptic ulcer in the Japanese in Hawaii is largely attributable to smoking and that smoking is more strongly related to gastric than duodenal ulcer. The especially strong link between cigarettes and gastric ulcer suggests that decreased smoking or synchronous decrease in cigarette tar content may have contributed to the recent unexplained decrease in male gastric ulcer.

Asian↗
PubMed1989

Methodological issues in comparing genetic and environmental influences on bone mass.

Measurements of bone mineral content (BMC), bone width (BW) and BMC/BW (BMA) at the proximal radius were compared for both Japanese and Japanese-American men and women, after adjusting for measurement technique differences. Within each nationality, men had greater values than women at all ages. Japanese-Americans had substantially greater values of BMC (6-10%) and BMA (16-17%), but lower BW (-12 to -15%), relative to Japanese. Adjustment for body size (height and weight) reduced the magnitude of these differences by approximately one-half for BMC, but had a smaller effect on BMA, and slightly increased the difference in BW. Comparison of these results to published data suggests that environmental factors may have influences on bone mass that are similar in magnitude to the effects of race. The need for additional studies to address potential methodological problems is discussed, using this and other reports as examples.

Adult↗
PubMed1989

Risk factors in middle age that predict early and late onset of coronary heart disease.

Twelve biological and lifestyle characteristics measured in a group of 5919 middle aged men free of clinical coronary heart disease (CHD), stroke and cancer were analyzed for differences in predicting early and late onset of new cases of definite CHD (non-fatal myocardial infarction and fatal CHD) over a 12-year follow-up period. Among these men, 151 cases of definite CHD occurred early (under age 60) and 135 cases occurred later in life (age 60 and over). Serum triglyceride was the only risk factor that was an independent predictor of early onset disease and not of late onset disease. While cigarette smoking was a predictor for both onset groups, the effect of smoking was greater in people who developed CHD earlier in life. Systolic blood pressure, alcohol intake, serum cholesterol and serum glucose were independent predictors for both onset groups, with no difference in effect between groups. The findings indicate that it is possible for some factors to affect CHD risk differently in terms of premature vs delayed onset of disease. The findings for serum triglyceride may account for some of the inconsistencies in reports regarding it as an independent risk factor for CHD. In general, however, most of the characteristics studied here had a similar effect on both early and late onset and thus remain important in the prevention of both premature and late onset of CHD.

Age Factors↗
PubMed1989

Regression of Q waves following acute myocardial infarction.

The predictors and effects of Q wave regression following acute Q wave myocardial infarction were examined in 1965-1982 in 127 Japanese-American men who participated in a prospective epidemiologic study of cardiovascular disease. Of these 127 men, 53 (42%) showed total regression of Q waves, 17 (13%) showed partial regression, and 57 (45%) showed no Q wave regression following acute myocardial infarction. Age at myocardial infarction and location of myocardial infarction did not predict which men would undergo Q wave regression. Q wave status after myocardial infarction (total, partial, or no regression) did not predict survival or recurrence of myocardial infarction. This study found that a substantial proportion of acute myocardial infarction cases undergo Q wave regression, indicating that clinicians and investigators alike require additional evidence to identify people with previous myocardial infarction.

Electrocardiography↗
PubMed1989

Pulmonary function as a predictor of coronary heart disease.

The role of pulmonary function as an independent predictor of coronary heart disease was examined in 1965-1983 in a cohort of Japanese-American men. As part of the Honolulu Heart Program, the authors measured pulmonary function in 5,924 men aged 45-68 years who were free of coronary heart disease at baseline examination and followed them for 15-18 years for the development of nonfatal myocardial infarction and fatal coronary heart disease. Per cent predicted forced expiratory volume in one second (%PFEV1) was significantly inversely related to coronary heart disease incidence in the total cohort after adjusting for age (p less than 0.0001) and then for all known coronary heart disease risk factors (p = 0.0004). However, when examined by smoking status, %PFEV1 was a predictor of coronary heart disease only among past and current smokers, and not for men who had never smoked cigarettes (p = 0.36). The association between pulmonary function and coronary heart disease can be explained by cigarette smoking, which leads to both lung impairment and coronary heart disease incidence.

Aged↗
PubMed1989

Predictors of sudden cardiac death among Hawaiian-Japanese men.

A cohort of 7,591 middle-aged Hawaiian-Japanese men free at initial examination of evidence of coronary heart disease or stroke were followed starting in 1965. Between 1965 and 1983, 1,342 of these men died; 229 deaths occurred less than 24 hours after the onset of the terminal episode, of which 98 deaths occurred in less than one hour. In the category of deaths occurring less than one hour after onset, the risk characteristics of those whose deaths were attributed to coronary heart disease and those whose deaths were attributed to an unknown cause were similar. It is appropriate to combine them as "sudden cardiac death." In the category of deaths occurring one to 24 hours after onset, the risk characteristics of those whose deaths were attributed to coronary heart disease and those whose deaths were attributed to an unknown cause differed. It is not appropriate to assume coronary heart disease as the underlying cause of death in this unknown cause group. The predictors of sudden cardiac death were blood pressure, serum cholesterol, serum glucose, cigarette smoking, history of parental heart attack, and electrocardiographic evidence of left ventricular hypertrophy or strain. Inversely related to risk were alcohol intake and the number of years spent in Japan. No factor distinguished those at risk for sudden cardiac death from those at risk for other manifestations of coronary heart disease.

Blood Glucose↗
PubMed1989

Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program.

During an average 18 years of follow-up for 7,850 Japanese-American men in Hawaii who were free of stroke at entry, 116 developed hemorrhagic stroke (subarachnoid hemorrhage or intracerebral hemorrhage). There was a significant (p = 0.001) inverse association between serum cholesterol and the risk of intracerebral hemorrhage but not of subarachnoid hemorrhage. This inverse association was nonlinear, with a higher incidence rate only for men with serum cholesterol in the lowest quintile (less than 189 mg/dl). The relative risk (lowest quintile/other four quintiles) was 2.55 (95% confidence interval 1.58-4.12) after controlling for age, blood pressure, serum uric acid, cigarette smoking, and alcohol consumption. There was no evidence for an interaction between blood pressure and serum cholesterol, although the inverse association was stronger for normotensive than for hypertensive men. Public health implications would differ in different countries depending on the relative frequency of intracerebral hemorrhage and on the distribution of serum cholesterol levels in the population.

Aged↗
PubMed1989

The incidence and prognosis of unrecognized myocardial infarction in the Honolulu, Hawaii, Heart Program.

The incidence of clinically unrecognized myocardial infarctions among 7331 Japanese-American men in Hawaii, aged 45 to 68 years and free of coronary heart disease at entry, was studied on the basis of electrocardiographic changes between successive examinations during 6 years of follow-up. The proportion of asymptomatic myocardial infarction accounted for 33% of transmural (Q-wave) myocardial infarctions identified by temporal changes on electrocardiogram and 22% of all nonfatal infarctions ascertained by either repeated examinations or hospital surveillance. The 10-year prognosis of unrecognized infarction, in terms of mortality from all causes, cardiovascular disease, and coronary heart disease, was worse (with risk ratios of 1.5 to 1.7) than that of recognized infarction, even after adjusting for age and other possible determinants, although the differences were not statistically significant. These findings suggest that regular health check-ups with an electrocardiogram would be important to detect asymptomatic myocardial infarction and to increase the opportunity of taking secondary preventive measures. However, the conclusion should await further studies based on intervention trials to determine the comparative effects of the secondary prevention on the prognosis of clinically recognized vs unrecognized infarction.

Aged↗
PubMed1989

Analyzing the relationship between age at onset and risk to relatives.

Correlations in age at onset between relatives affect risk to relatives of a given age. Either an increase or a decrease in risk may be observed for a relative of a proband, according to whether there is a causal relationship between liability to disease and age at onset. Likelihood formulas are given for pairs of relatives under a number of different sampling schemes, and it is shown how data collected from relatives enable maximum-likelihood estimation of parameters of a linear model relating disease liability and age at onset. A genotype-environment extension of this model was fitted to data on age at onset for schizophrenia that were obtained from the National Academy of Sciences-National Research Council Twin Registry. Age at onset is correlated between twins, but this correlation appears to be associated with factors that are separate from those which affect liability to disease. However, even this relatively large sample of twins is too small to draw firm conclusions about any causal relationship between disease liability and onset.

Age Factors↗
PubMed1988

A comparison of the 12-year mortality and predictive factors of coronary heart disease among Japanese men in Japan and Hawaii.

The mortality and predictive factors of coronary heart disease among men of Japanese ancestry in Japan and Hawaii were compared on the basis of 12 years follow-up data using comparable methods of case ascertainment and risk factor measurements. Among 1,687 men (Japan) and 7,536 men (Hawaii) who were free of coronary heart disease and aged 45-69 at baseline examination in 1965-1968, 20 (Japan) and 123 (Hawaii) cases of fatal coronary heart disease were identified. The age-adjusted mortality rate was 40% higher in Hawaii than in Japan. The difference was not statistically significant, but consistent with earlier studies. More than half of this difference in mortality rate was attributed to different levels of known risk factors in the two cohorts. In multivariate analysis using the combined population, age, blood pressure, serum cholesterol, serum glucose, cigarette smoking, and alcohol intake (inversely) remained as significant predictors of coronary heart disease mortality. Although the associations of risk factors with coronary heart disease tended to be stronger in Hawaii than in Japan, there was no statistically significant difference in regression coefficient for any of the risk factors studied. These findings cannot be claimed to be definitive because of the small number of cases, especially in Japan.

Actuarial Analysis↗
PubMed1988

Assessing changes in risk factor effect over multiple levels of severity.

Use of the logistic function has become standard for regression of proportions onto risk factors, but where multiple levels of response are recorded, several different techniques are common. For most purposes, the "inclusive" method is most appropriate. However, if investigation is focused directly on the pattern of risk factor effects over levels of severity, the inclusive method is too conservative, because its overlapping categories tend to minimize any real differences among risk factor effects at separate levels. Several alternative techniques maximize these estimated differences, but interpretation of their results is much more sensitive to the assumed model than is estimation of category frequencies. In most cases, it is not possible to know precisely what model actually generated the data at hand. Therefore, a procedure is recommended which combines the safety of the inclusive method with an adjuvant technique called the "continuation ratio" method which has greater power to disclose differences between risk factor effects at different levels of response.

Coronary Disease↗
PubMed1988

A prospective study of mortality and morbidity among carpenters in the Honolulu Heart Program Cohort.

The relationship of occupation as a carpenter to the development of definite coronary heart disease, stroke, cancer and total mortality was examined in men of Japanese ancestry participating in the Honolulu Heart Program. After 18 years of follow-up those men who indicated that their present and usual occupation was carpentry had a significantly lower age-adjusted rate of definite coronary heart disease and a significantly lower mortality rate compared to participants who were never occupied as carpenters. There were no significant differences for age-adjusted rates for stroke and cancer nor any differences for those whose usual occupation was carpentry but present occupation was not carpentry. These results were unchanged when controlling for several cardiovascular risk factors and potentially confounding variables. Unlike earlier observations, these findings are not affected by the "healthy worker bias" and support the relationship that carpentry is associated with lower rates of cardiovascular disease.

Cerebrovascular Disorders↗