摘要:

AbstractLow‐density lipoprotein (LDL) subclass phenotype B, characterized by a predominance of small, dense LDL particles, appears to be a genetically influenced risk factor for coronary heart disease. Phenotype B, as determined by gradient gel electrophoresis, appears to be inherited in a manner consistent with the presence of a single major genetic locus, based on complex segregation analysis. Familial combined hyperlipidemia (FCHL) is a disorder characterized by elevations in total plasma cholesterol and/or triglyceride levels in probands and family members, variable lipoprotein phenotypes over time, and elevations in apolipoprotein B levels. Because apo B is the primary protein component of LDL particles, the present study was undertaken to determine whether LDL subclass phenotypes are controlled by the APOB locus in FCHL families. The evidence against linkage was very strong based on lod score analyses (total lod = −13.3), under assumptions that LDL subclass phenotypes are influenced by a major genetic locus and that the mode of inheritance and penetrance functions are known. Other methods requiring fewer assumptions also provided evidence against linkage, although the strength of this evidence was weaker. Thus the results demonstrate that the proposed gene responsible for LDL subclass phenotypes is unlikely to be the APOB gene in families with F

ISSN:0741-0395    

DOI:10.1002/gepi.1370080502

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

年代:1991

数据来源: WILEY

摘要:

AbstractMost major genes involved in the etiology of complex diseases are likely to have pleiotropic effects on a number of intervening quantitative traits. Methods of segregation analysis that incorporate the additional information from such multiple traits will exhibit greater power for detecting the effects of major genes and allow explicit tests of major locus pleiotropy hypotheses. In this study, we present a new method for multivariate segregation analysis that utilizes a multivariate generalization of Hasstedt's [1982] technique for calculating approximate mixed model likelihoods on pedigrees. The method is based on a simplification of the multivariate conditional likelihood via a transformation that simultaneously orthogonalizes the residual additive genetic and environmental covariance matrices. This transformation allows the multivariate conditional likelihood to be factored into the product of independent univariate conditional likelihoods. Resulting computations are relatively fast, making it feasible to analyze multiple traits in extended pedigrees. We demonstrate our method with a bivariate analysis of high‐density lipoprotein cholesterol (HDL‐C) and apolipoprotein AI (apo AI) serum levels in 585 pedigreed babo

ISSN:0741-0395    

DOI:10.1002/gepi.1370080503

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

年代:1991

数据来源: WILEY

摘要:

AbstractCases of interest using affected sib‐pair methods to distinguish between recessive and additive (dominant) modes of inheritance of a disease‐predisposing gene involve goodness‐of‐fit tests with a small expected number in the “share‐zero parental haplotypes” category, as well as an unknown parameter, the frequency of the disease‐predisposing allele. Our simulations demonstrate that the real significance level of the chi‐square test using the three‐haplotype‐sharing IBD values (share 2, 1, and 0 parental haplotypes) is close to the assumed (.05) level in these cases, so that the haplotype‐sharing classes do not have to be lumped, which would leave no degrees of freedom for a statistical test. The validity of the chi‐square approximation in cases of small expected freqencies has previously been described, but the situations that have been considered do not cover the very small values in the share‐zero category that are often expected in the affected sib‐pair analysis, nor do they involve estimation of an unknown parameter. Although including IBD values from affected kin pairs other than sibs can be a very powerful tool in demonstrating linkage of a marker and disease, these pairs do not add power, in fact they reduce the power, of the chi‐square tests of goodness

ISSN:0741-0395    

DOI:10.1002/gepi.1370080504

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

年代:1991

数据来源: WILEY

摘要:

AbstractFamily studies with age at onset of the disease as the endpoint face two important problems: censoring and correlation of age at onset among relatives. We present a multivariate survival model for ages at onset of relatives which incorporates the problems cited above. The interpretations of regression coefficients and association parameter in the context of family studies are emphasized. The present paper describes a statistical method for estimating these parameters. In a companion paper [Pulver and Liang,Genet Epidemiol8:339–350, 1991] this model is applied to a genetic epidemiologic study of schizophreni

ISSN:0741-0395    

DOI:10.1002/gepi.1370080505

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

年代:1991

数据来源: WILEY

摘要:

AbstractIn this report we apply methods outlined in the companion paper [Liang,Genet Epidemiol8:329–338, 1991] to study the association between proband age at onset and familial risk among first‐degree relatives of 374 schizophrenic probands. The analyses take into consideration the potential problems of censoring and correlation of age at onset within families. All analyses were done by gender of the proband; age at onset was dichotomized. The results of the analyses of the male probands suggest that there is an increased risk of schizophrenia among the relatives of male probands who have an onset prior to age 17 when compared to relatives of male probands who have an onset later than 16. We did not find an association between age at onset and familial risk among the female probands, but this may be due to the smaller number of female probands and the lower power associated with the analy

ISSN:0741-0395    

DOI:10.1002/gepi.1370080506

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe genetics of basal total serum IgE levels was investigated in 278 individuals from 42 randomly ascertained nuclear families. The data were analyzed using the regressive model approach to segregation analysis with age, sex, and a measure of skin test responsiveness as covariates in the Class D models. The best fitting model was that of recessive inheritance of high IgE levels with a gene frequency of 0.99 for the “high” allele. Only 3 families showed evidence for segregation of the rare “low” allele, and, if extended further, these families could be useful for molecular genetic linkage studies. These results suggest that there may be a rare allele for very low total serum IgE levels that can be detected even after a measurement of allergic responsiveness (skin test results) is considered as a covariate. Therefore, this major gene for IgE levels appears independent of any similar locus controllin

ISSN:0741-0395    

DOI:10.1002/gepi.1370080507

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

年代:1991

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370080501

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

年代:1991

数据来源: WILEY