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K Y Liang

Publications and source records attributed to K Y Liang.

At least 55 records · Page 3Linked to original sources

Comparison of methods for survival analysis of dependent data.

Analysis of dependent survival data by conventional partial likelihood methods produces unbiased estimates of the regression coefficients but incorrectly estimates their variance. Here we compared the conventional partial likelihood methods with two alternative methods for analyzing dependent survival data. The first alternative method estimated the regression coefficient by the partial likelihood approach but adjusted the variance to account for clustering. The second alternative method used marginal likelihoods to estimate both the regression coefficient and its variance. We evaluated the performance of the three methods using simulated and actual data. Simulated data were used to examine bias, efficiency, type I errors, and power. An Old Order Amish genealogy was analyzed under these models to illustrate their performance on real data. The simulation study showed that all three methods provided unbiased estimates of the regression coefficient, but the efficiency of the estimated regression coefficient varied according to the simulation conditions. The standard partial likelihood method showed increasing type I error as the dependence increased within clusters. Both alternative methods had acceptable levels of type I errors at all dependence levels. In the analysis of genealogic data, the regression coefficient was similar in the three methods showing stable estimates of the regression coefficients. The variance estimates from the alternative methods were slightly different from the conventional method, suggesting a flow level of dependence. This study displays the effect of violating the independence assumption and provides guidelines for using alternative statistical methods.

Analysis of Variance↗

Analysis of case-control/family sampling design.

A commonly adopted design in genetic epidemiologic studies is the so-called case-control/family sampling design. Here, cases and controls are sampled and response variables, either quantitative or qualitative, for relatives of cases are contrasted with those of control relatives. This design can be used to examine familial aggregation, contribute to identification of genetic subtypes, and test the discrete versus continuous spectrum hypothesis for disorders of unknown etiology. However, the statistical independence assumption required by conventional case-control studies is violated for observations from related individuals who share the same genetic/environmental conditions. Consequently, ignoring dependence among related subjects will lead to incorrect sample size calculations and potentially erratic scientific conclusions. In this paper, we discuss several statistical issues that are relevant to the case-control/family sampling design with a focus on the use of this design in psychiatric research. Specifically, we 1) discuss the relative merit of matched versus unmatched designs; 2) present statistical methods that are useful for analyzing family data and 3) present sample size formulas for studies of quantitative and qualitative traits. A genetic epidemiologic study of schizophrenia is used for illustrative purposes.

Adolescent↗

Determining linkage and mode of inheritance: mode scores and other methods.

The lod score method remains a popular approach for detecting linkage and estimating the recombination fraction theta between a marker locus and a trait locus. However, its implementation requires knowledge of all parameters of the genetic mechanism, including the number of loci involved and the genotype specific penetrance, which could depend on factors such as age. When some of the penetrance parameters phi are unknown, several methods are available, and have been reviewed by Hodge and Elston [(1994) Genet Epidemiol 11:329-342]. These include the "wrod score" (lod score maximized over theta under a wrong value of phi) and "mod score" (lod score maximized over both theta and phi) methods for inference on theta. It has further been proposed that the mod score also be used for estimating phi. In this paper, we review and assess the adequacy of these two methods for inferences on both phi and theta. In particular, all of the methods can be seen as variations on likelihood inference, using the information in the conditional likelihood for the marker data, given the trait data. The loss of efficiency of the mod is compared to that of the full likelihood, which utilizes all information available in the trait data. We also propose an alternative, based on the pseudo-likelihood, where phi is estimated via the trait information and plugged into the conditional likelihood. This method is compared to the mod score method, and the advantages and disadvantages of each are elucidated. In particular, it is seen that the pseudo-likelihood method can be more efficient than the mod score method if the ascertainment scheme can be modeled. As examples, both a random sample and a multiplex ascertainment scheme are considered. In addition, the pseudo-likelihood method leads to likelihood ratio tests for detecting linkage with a simple, known asymptotic reference distribution, a feature not shared by the mod score. Finally, we discuss the advantages of using the pseudo-likelihood method over the full likelihood method, both of which are valid when the ascertainment scheme is known.

Genetic Linkage↗

Quasilikelihood estimation in measurement error models with correlated replicates.

We consider quasilikelihood models when some of the predictors are measured with error. In many cases, the true but fallible predictor is impossible to measure, and the best one can do is to obtain replicates of the fallible predictor. We consider the case that the replicates are not independent. If one assumes that replicates are independent and they are not, one typically underestimates the extent of the measurement error, leading to an inconsistent errors in variables correction. We devise techniques for estimating the measurement error covariance matrix. In addition, we discuss how one might perform a quasilikelihood analysis by computing the mean and variance functions of the observed data, both using approximations and also exactly through a Monte Carlo method. The methods are illustrated on a data set involving systolic blood pressure and urinary sodium chloride, where the measurement errors appear to be approximately normally distributed but highly correlated, and the distribution of the true predictor is reasonably modeled as a mixture of normals.

Analysis of Variance↗

Structure and course of positive and negative symptoms in schizophrenia.

BACKGROUND: This article focuses on the underlying structure and temporal course of the symptoms of schizophrenia. METHODS: Ratings of symptoms in 90 schizophrenic patients were made each month for 10 years following the first hospitalization. The analytic methods consisted of cross-tabulation, dichotomous factor analysis, and bivariate dichotomous time series. RESULTS: The factor analyses revealed positive and negative factors with a slight tendency to merge over time. The prevalence of positive and negative symptoms declined in the year following first hospitalization and was stable thereafter. Positive and negative symptoms in 1 month were highly predictive of the same type of symptoms in the next month. Neither type of symptom was strongly associated with the other type in the following month when both types were included in the model. The predictability of the process increased with time. CONCLUSIONS: With a few minor caveats, the results suggest that the positive and negative symptom clusters are independent, both cross-sectionally and longitudinally.

Adult↗

Some recent developments for regression analysis of multivariate failure time data.

Cox's seminal 1972 paper on regression methods for possibly censored failure time data popularized the use of time to an event as a primary response in prospective studies. But one key assumption of this and other regression methods is that observations are independent of one another. In many problems, failure times are clustered into small groups where outcomes within a group are correlated. Examples include failure times for two eyes from one person or for members of the same family. This paper presents a survey of models for multivariate failure time data. Two distinct classes of models are considered: frailty and marginal models. In a frailty model, the correlation is assumed to derive from latent variables ("frailties") common to observations from the same cluster. Regression models are formulated for the conditional failure time distribution given the frailties. Alternatively, marginal models describe the marginal failure time distribution of each response while separately modelling the association among responses from the same cluster. We focus on recent extensions of the proportional hazards model for multivariate failure time data. Model formulation, parameter interpretation and estimation procedures are considered.

Clinical Trials as Topic↗

Sudden infant death syndrome in relation to weather and optimetrically measured air pollution in Taiwan.

OBJECTIVE: To examine the possible role of weather and air pollution in sudden infant death syndrome (SIDS) and suffocation. METHODS: Poisson regression analysis was carried out to measure the association between daily rates of SIDS per 1000 live births and daily average values of visibility and temperature in Taiwan between 1981 and 1991. The optimetrical measure of air pollution was used to represent pollution over a whole area rather than at a point source. RESULTS: Mortality from SIDS per 1000 live births was 3.3 times greater in the lowest category of visibility on the day of death than in the highest category; this rate ratio was 3.4 for the average visibility during the 9 days before death. Adjustment for population size, season, level of urbanization, incidence of deaths from respiratory tract infections, temperature, air pressure, sunshine, rainfall, relative humidity, and windspeed increased these rate ratios to 3.8 and 5.1, respectively. This suggests that the relationship between air pollution and SIDS is not biased by ecological confounders. For temperature the rate ratios were between 3.3 and 4.0. CONCLUSIONS: Our findings confirm the association of climatic temperature and air pollution with SIDS.

Air Pollution↗

Minimum sample size estimation to detect gene-environment interaction in case-control designs.

As genetic markers become more available, case-control studies will be increasingly important in defining the role of genetic factors in disease causality. The authors estimate the minimum sample size needed to assure adequate statistical power to detect gene-environment interaction. One assumption is made: the prevalence of exposure is independent of marker genotypes among controls. Given the assumption, six parameters (three odds ratios, the prevalence of exposure, the proportion of those with the susceptible genotype, and the ratio of controls to cases) dictate the expected cell sizes in a 2 x 2 x 2 table contrasting genetic susceptibility, exposure, and disease. The three odds ratios reflect the association between disease and 1) exposure among non-susceptibles; 2) susceptible genotypes among nonexposed individuals; and 3) the gene-environment interaction itself, respectively. Given these parameters, the number of cases and controls needed to assure any particular Type I and Type II error rates can be estimated. Results presented here demonstrate that case-control designs can be used to detect gene-environment interaction when there is both a common exposure and a highly polymorphic marker of susceptibility.

Case-Control Studies↗

Extended latent class approach to the study of familial/sporadic forms of a disease: its application to the study of the heterogeneity of schizophrenia.

When no method exists for detecting genetic forms of a disorder, epidemiologists classify probands according to the presence or absence of an affected relative (familial or sporadic). Not only is this a surrogate measure but if the risk for the disorder is associated with characteristics such as age and gender, then probands with varied distributions of these characteristics among their relatives are subject to misclassification. A latent class approach is presented which explicitly models the relationship between the affected status of the relatives and the unobservable familial/sporadic status of the proband in order to adjust for these characteristics. Lastly, an approach is introduced to correct for attenuation in measures of association between familial/sporadic status and other variables that could result if probands are misclassified. This approach incorporates the latent class probabilities directly into the regression model without classifying probands. These methods are applied to a study of the heterogeneity of schizophrenia.

Adolescent↗

Temperament as a potential predictor of mortality: evidence from a 41-year prospective study.

Psychological factors were hypothesized to influence mortality, in particular, early versus later mortality. To explore the relationship between temperament, a psychological factor, and mortality in a prospective study of 1337 medical students, we constructed a measure portraying three temperament types, using latent class analysis. Death occurred in 113 subjects over 25-41 years of follow-up. In univariate survival analysis, subjects tending to direct tension "inward" when under stress ("Tension-In") had a higher risk of mortality than "Tension-Out" or "Stable" types. These associations persisted after adjustment for age, smoking, cholesterol level, and Quetelet Index. The relative risk (RR) of mortality for Tension-In was 1.56 (95% confidence interval, 1.00-2.44) compared with the Stable group. The risk was due entirely to the excess risk in persons under 55 years of age (RR, 2.59; 95% confidence interval, 1.46-4.62); the corresponding risk of death in older persons was 0.66 (0.30-1.48). Thus temperament is a significant risk factor for mortality, in particular, premature death.

Adult↗

Coffee intake and coronary heart disease.

We examined the risk of coronary heart disease (CHD) associated with coffee intake in 1040 male medical students followed for 28 to 44 years. During the follow-up, CHD developed in 111 men. The relative risks (95% confidence interval) associated with drinking 5 cups of coffee/d were 2.94 (1.27, 6.81) for baseline, 5.52 (1.31, 23.18) for average, and 1.95 (0.86, 4.40) for most recent intake after adjustment for baseline age, serum cholesterol levels, calendar time, and the time-dependent covariates number of cigarettes, body mass index, and incident hypertension and diabetes. Risks were elevated in both smokers and nonsmokers and were stronger for myocardial infarction. Most of the excess risk was associated with coffee drinking prior to 1975. The diagnosis of hypertension was associated with a subsequent reduction in coffee intake. Negative results in some studies may be due to the assessment of coffee intake later in life or to differences in methods of coffee preparation between study populations or over calendar time.

Adult↗

On the use of the quasi-likelihood method in teratological experiments.

This paper concerns the impact of litter effects on the inference of dose-response relationships in teratological experiments with binary response. Kupper et al. (1986, Biometrics 42, 85-98) concluded that when intra-litter correlations are dose-dependent, the use of a common intra-litter correlation likelihood based on the beta-binomial distribution could lead to severe bias in estimation of the parameter beta, which characterizes the dose-response relationship. We show here that the problems of bias and coverage probability for beta could still be substantial when one uses the likelihood with heterogeneous intra-litter correlations. We then examine through a simulation study the performance of the quasi-likelihood method (Wedderburn, 1974, Biometrika 61, 439-447) and recommend that this method with a common intra-litter correlation parameter be used when the number of litters is small or modest.

Analysis of Variance↗

Appropriate statistical methods to account for similarities in binary outcomes between fellow eyes.

PURPOSE: Many ocular measurements are more alike between fellow eyes than between eyes from different individuals. To make appropriate inferences using data from both eyes rather than the best or worst eye, statistical methods that account for the association between fellow eyes must be used. METHODS: Marginal and conditional regression models account for the association between fellow eyes in different ways. The authors compare and contrast these methods using data from a series of patients with retinitis pigmentosa in whom the primary object is to identify risk factors, some of which are subject specific and some of which are eye specific, for visual acuity loss (as a binary outcome) among affected subjects. RESULTS: Odds ratios for age, gender, presence of posterior subcapsular cataract, and genetic type of retinitis pigmentosa obtained from the marginal model were all larger than those from the conditional model. Familial aggregation of visual acuity loss was statistically significant in the marginal, but not in the conditional, model. CONCLUSIONS: The estimates and interpretation of the association between an ocular outcome and risk factors can differ significantly between these two approaches. The choice of model depends on the scientific questions of interest rather than on statistical considerations. Computer programs are available for implementing both models.

Baltimore↗

Serum cholesterol in young men and subsequent cardiovascular disease.

BACKGROUND: The increased risk of cardiovascular disease associated with higher serum cholesterol levels in middle-aged persons has been clearly established, but there have been few opportunities to examine a potential link between serum cholesterol levels measured in young men and clinically evident premature cardiovascular disease later in life. METHODS: We performed a prospective study of 1017 young men (mean age, 22 years) followed for 27 to 42 years to quantify the risk of cardiovascular disease and total mortality associated with serum cholesterol levels during early adult life. The mean serum cholesterol level at entry was 192 mg per deciliter (5.0 mmol per liter). RESULTS: During a median follow-up of 30.5 years, there were 125 cardiovascular-disease events, 97 of which were due to coronary heart disease. The serum cholesterol level at base line was strongly associated with the incidence of events related to coronary heart disease and cardiovascular disease, as well as to total mortality and mortality due to cardiovascular disease. The risks were similar whether the events occurred before or after the age of 50. In a proportional-hazards analysis adjusted for age, body-mass index (the weight in kilograms divided by the square of the height in meters), the level of physical activity, coffee intake, change in smoking status, and the incidence of diabetes and hypertension during follow-up, a difference in the serum cholesterol level at base line of 36 mg per deciliter (0.9 mmol per liter)--the difference between the 25th and 75th percentiles of cholesterol level in the study population at base line--was associated with an increased risk of cardiovascular disease (relative risk, 1.72; 95 percent confidence interval, 1.39 to 2.14), coronary heart disease (relative risk, 2.01; 95 percent confidence interval, 1.59 to 2.53), and mortality due to cardiovascular disease (relative risk, 2.02; 95 percent confidence interval, 1.23 to 3.32). A difference in the base-line serum cholesterol level of 36 mg per deciliter was significantly associated with an increased risk of death before the age of 50 (relative risk, 1.64; 95 percent confidence interval, 1.03 to 2.61), but not with the overall risk of death (relative risk, 1.21; 95 percent confidence interval, 0.93 to 1.58). CONCLUSIONS: These findings indicate a strong association between the serum cholesterol level measured early in adult life in men and cardiovascular disease in midlife.

Adult↗

Familial aggregation of periodontal indices.

Analysis of three measures of periodontal health (plaque index, gingival index, and attachment loss) was carried out on 178 individuals in 75 families examined as part of a family study of periodontal health. Original participants in this study were volunteers recruited from the University of Maryland Dental Clinic, and were selected independently of any specific dental disease or condition. Relatives were invited to participate in the family study so that the extent of familial aggregation of indices of periodontal health could be assessed. By means of an analysis of variance model for persons nested within families, evidence for familial aggregation of plaque index was found both before and after adjustment for covariates such as age, gender, race, and reported oral hygiene habits. While a substantial fraction of variance in gingival index and attachment loss was also due to differences among families, neither attained statistical significance in these data. Examination of familial correlations (e.g., parent-offspring, sib-sib, spouse correlations) confirmed that plaque index showed greater familial resemblance compared with other measures of periodontal health. Both mean gingival index and mean attachment loss showed a stronger correlation between mothers and offspring compared with fathers and offspring. This suggests that further analysis of models for separating genetic and environmental effects may be appropriate for plaque index, but complete analysis of other periodontal indices will require more flexible statistical models for separation of genetic and cultural inheritance while considering gender-specific expression and transmission, as well as incorporation of information from covariates.

Adolescent↗

Case studies in binary dispersion.

It is common in biomedical studies with binary responses that variability in the observed number of events exceeds binomial variability, a phenomenon known as overdispersion. Failure to make an adjustment to the nominal standard errors can lead to seriously misleading inference for regression analysis. In this note, we examine a series of examples drawn from the literature to see which of two commonly used variance formulas is more adequate for describing overdispersion in applications. Two methods, residual analysis and formal comparison, are introduced. We recommend that both methods be employed in seeking an appropriate variance expression for binary responses. Each of the five data sets exhibits substantial overdispersion, one favoring the beta-binomial form, another favoring a constant overdispersion factor. The remaining three examples exhibit no preference.

Animals↗

Vascular reactivity in young adults and cardiovascular disease. A prospective study.

Cardiovascular reactivity in response to the cold pressor test has been associated with an increased risk of coronary heart disease in middle-aged men. We studied 905 white male medical students, median age 22 years, in the Johns Hopkins Precursors Study. Systolic blood pressure, systolic blood pressure change during the cold pressor test, smoking, cholesterol, Quetelet index, and family history of coronary heart disease were measured on enrollment during 1948-1964. Incidence of cardiovascular morbidity and mortality was ascertained by annual questionnaires and death certificates. There was no association between change in systolic blood pressure during the cold pressor test, whether examined as a continuous variable or a 20 mm Hg or more rise, and the risk of subsequent cardiovascular disease or coronary heart disease. These findings did not change after adjustment for cardiovascular disease risk factors. Previously reported associations may have been due to preexisting arteriosclerosis, which increases the rise in systolic blood pressure during the cold pressor test. We conclude that cardiovascular reactivity to the cold pressor test in young adulthood is not a strong predictor of future cardiovascular disease.

Adult↗