摘要:

AbstractA model is presented for the effects of one or two loci, a measured index of the environment and genotype × environment (G×E) interaction of risk for a discontinuous trait. Initial properties of the model are explored for the single locus case, with and without the effects of environment and G×E interaction. Seven data sets were simulated, each comprising 500 nuclear families on whom an environmental index has been measured. Maximum‐likelihood estimation procedures were used to obtain parameter estimates under seven models for each data set. Likelihood ratio tests were constructed, and in all cases it was possible to identify the “correct” model for the simulated data. The matrices of information realized showed that the parameters could be estimated with acceptable precision and that the effects of genes, environment, and G×E interaction could be resolved in the simulated populations. The effects on conventional segregation analysis of ignoring the environment and G×E are

ISSN:0741-0395    

DOI:10.1002/gepi.1370010302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractIt is often of interest to know whether there is increased occurrence of a trait in a pedigree or other structured set of epidemiological data. In answering such questions most current methods use aggregate measures, such as relative risk, that may not relate the outcome for each individual to that individual's risk. In this paper we present a simple method, and its computational algorithm, to overcome this limitation. This new method also permits one to identify high‐risk families or subsets of a collection of data, which is not always possible using other approaches.In a study of cancer risk among relatives of retinoblastoma patients, by applying this new method it was found that 11 of 33 families each obtained through a unilateral retinoblastoma patient are at statistically high risk of cancer at all sites combined, while there are 15 of 47 such families obtained through a bilaterally affected proband. These results are unlikely to have occured by chance, indicating an overall excess risk in the ancestors of these retinoblastoma cases.The proposed test procedure does not specify the cause of elevated risk; however, a method is proposed that provides some indication regarding possible causal mechanisms under some circumstance

ISSN:0741-0395    

DOI:10.1002/gepi.1370010303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractAlthough stuttering is known to be a familial disorder, no clear evidence regarding precise mode of transmission has arisen from previous research. In this report segregation analysis is applied to data on 386 stuttering probands and their first‐degree relatives in an effort to discriminate among possible genetic models for the transmission of stuttering. Two different segregation analysis programs, PAP and POINTER, gave comparable results with respect to both hypothesis testing and parameter estimation. Specifically, the transmission of stuttering observed in these families cannot be adequately explained by a Mendelian major locus. The hypothesis of no polygenic component in the transmission of stuttering can, however, be rejected. Existence in these data of potential heterogeneity and possible violations of assumptions concerning ascertainment are considered in interpreting the result

ISSN:0741-0395    

DOI:10.1002/gepi.1370010304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractPath analysis of family data has been widely applied to resolve genetic and environmental patterns of familial resemblance. A prevalent statistical approach in path analysis has been, first, to estimate the familial correlations and, second, by assuming these estimates to be independently distributed, define a likelihood function from which maximum likelihood estimates of model parameters can be obtained and likelihood ratio tests of hypotheses performed. Although it is generally known that the independence assumption does not hold when multiple familial correlations are estimated from the same family data, this statistical method has still been used in these situations owing, in part, to the lack of any viable alternatives and, in part, to the lack of any knowledge about the specific quantitative effects of not meeting the assumption of independence. Here, using computer‐simulation methods, we evaluate the robustness of this statistical method to deviations from the assumption of independence. In general, we found that the failure to meet the assumption of independence leads to a conservative test of the goodness‐of‐fit of the path model, although likelihood ratio tests of specific null hypotheses were at times liberal, at times conservative, and at times nearly exact. Although the test statistics were found to be distorted, the parameter estimates using this method were nearly unb

ISSN:0741-0395    

DOI:10.1002/gepi.1370010305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractAn analysis of hydatidiform moles occurring in Hawaii over a 14‐year period (1968–1981) was undertaken. The pathology of all 278 reported molar pregnancies was reviewed and showed 69.4% to be complete, 24.5% to be partial, and 6.1% to be nonmolar.A case‐control epidemiological investigation of the complete moles showed maternal age and race to be important, moles being significantly more prevalent in women under 20 and over 40 yr of age and also in women of Japanese, Filipino, and other Oriental ancestry. However no difference was seen in the prevalence of moles between Oriental women born in the Orient and those born and raised in Hawaii. No significant difference was found in paternal age, paternal race, socioeconomic status, or reproductive history, suggesting that these factors do not play an important role in the etiology of complete hydatidiform mole.Incidence rates for complete moles were calculated taking age and race into consideration and ranged from a high of 1 in 150 to a low of 1 in 2,000 naturally terminating pregna

ISSN:0741-0395    

DOI:10.1002/gepi.1370010306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractSimulated multigenerational pedigrees were analyzed using the program GENPED and POINTER to examine the 1) limits of segregation analysis for detecting single locus, two‐allele transmission of a dichotomous trait and 2) accuracy of the parameter estimates. Ten data sets of 30 pedigrees each (approximately 25 persons per pedigree) were simulated. The genotypic penetrance values were varied but the population prevalence of the trait was kept constant at 2%. For some data sets a linked marker locus was also simulated. Previous results had shown that a single major locus could be easily detected when the heterozygote penetrance (f1) was high or midway between the two homozygote penetrances. In this study, we found a single major locus could not be consistently detected by either method of segregation analysis when f1was “low” to “intermediate.” Accuracy of the parameter estimates depended on assumptions about the population prevalence. In those cases where the major locus could not be detected by segregation analysis, linkage to a marker locus could be detected as long as the marker was closely linked and there were not phenocopies in the population. Owing to the limited number of simulations in this study, we cannot generalize these findings. However, they provide a basis for further testing of methods of segregation analysis when factors such as the parameter values, family structure, and ascertainment scheme a

ISSN:0741-0395    

DOI:10.1002/gepi.1370010307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370010301

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY