摘要:

AbstractWe show that under the null hypothesis of no linkage the maximum likelihood estimator of the recombination fraction converges to 1/2 even when the trait‐related parameter values in the likelihood function are misspecified. Furthermore, we show that under the null hypothesis of no linkage, but with misspecified trait‐related parameter values, the negative of twice the natural logarithm of the likelihood ratio statistic still has a limiting chi‐square distribution with 1 degree of fr

ISSN:0741-0395    

DOI:10.1002/gepi.1370070502

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe regressive models describe familial patterns of dependence of quantitative measures by specifying regression relationships among a person's phenotype and genotype and the phenotypes and genotypes of antecedents. When the number of sibs in the pattern of dependence increases, as in the class D regressive model, computation of the likelihood becomes time consuming, since the Elston‐Stewart algorithm cannot be used generally. On the other hand, the simpler class A regressive model, which imposes a restriction on the sib‐sib correlation, may lead to inference of a spurious major gene, as already observed in some instances. A simulation study is performed to explore the robustness of class A model with respect to false inference of a major gene and to search for faster methods of computing the likelihood under class D model. The class A model is not robust against the presence of a sib‐sib correlation exceeding that specified by the model, unless tests on transmission probabilities are performed carefully: false detection of a major gene is reduced from a number of 26–30 to between 0 and 4 data sets out of 30 replicates after testing both the Mendelian transmission and the absence of transmission of a major effect against the general transmission model. Among various approximations of the likelihood formulation of the class D model, approximations 6 and 8 are found to work appropriately in terms of both the estimation of all parameters and hypothesis testing, for each generating model. These approximations lessen the computer time by allowing use of the Elston‐Stewart

ISSN:0741-0395    

DOI:10.1002/gepi.1370070503

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

年代:1990

数据来源: WILEY

摘要:

AbstractThis study examines the independent and interactive effects of family history scores (FHxS) for the prevalence of ischemic heart disease with plasma lipids and subsequent morbidity and mortality from ischemic heart disease. FHxS were calculated for 514 sets of middle aged male twins who participated in the entry examination of the NHLBI Veteran twin study in 1969–1973. Comparison of the FHxS with the level of plasma total cholesterol and HDL cholesterol (HDLc) paralleled earlier reported findings in young adults; individuals with high total cholesterol in two exams 8–12 years apart had significantly (P<.01) higher FHxS. The same relationship was noted when using the mean twin‐pair cholesterol level at the initial exam when the twins were in their 40s. Using the pair means over two exams as the cotwins aged into their 50s, the association of FHxS with total cholesterol declined and pairs with HDLc persistently in the highest quintile at both exams had significantly (P<.01) lower FHxS. The changes in the pattern of association of lipid fractions with FHxS with age parallel the reported age decline of total cholesterol as a risk factor for heart disease. Assessment of ischemic heart disease events up to January 1988 revealed a highly significant association (P<.0001) of later ischemic heart disease events with FHxS. At each level of lipid categorization pairs who later had events had higher FHxS than those without any subsequent heart disease; these differences were significant in all but the low risk lipid groups (low total cholesterol, high HDLc, and low total cholesterol/HDLc ratio). We conclude that FHxS is related to total cholesterol and HDLc but also is an independent predictor of subsequent ischemic heart disease after 14–18 years of fo

ISSN:0741-0395    

DOI:10.1002/gepi.1370070504

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

年代:1990

数据来源: WILEY

摘要:

AbstractA major difficulty in a linkage analysis arises from the necessity of specifying the mode of inheritance prior to analysis. For a complex disease, such as those encountered in psychiatric illnesses, the mode of inheritance is generally not known in advance. Consequently, some estimation procedure is often combined with linkage analysis to circumvent this. We discuss several precautions that should be taken when using traditional statistical testing methods: correction of the likelihood for the method of sampling families and the computation of the lod score. We analyze simulated data with pedigrees selected under a sampling scheme approximating single ascertainment. In this situation, the severity of the above problems is attenuated.

ISSN:0741-0395    

DOI:10.1002/gepi.1370070505

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

年代:1990

数据来源: WILEY

摘要:

AbstractSeveral statistical tests for linkage between a disease susceptibility locus and a marker locus for sib‐pair data are examined analytically. Two common statistics, a test based on the mean number of marker alleles shared identical by descent by sib‐pairs, and a test based on the proportion of sib‐pairs sharing exactly two marker alleles, are shown to be special cases of a more general statistic. We use this more general statistic to derive the asymptotically most powerful statistic for a given genetic alternative hypothesis, and then compare this statistic with the “mean” statistic and the “proportion” statistic. Results indicate that the “mean” statistic generally compares well with the most powerful statistic. However, in some instances the “mean” statistic may lose power, relative to the most powerful. To guard against this, a new statistic (the maximum of the “mean” and “proportions” statistics) is considered and its asymptotic distribution is derived. Results indicate that thi

ISSN:0741-0395    

DOI:10.1002/gepi.1370070506

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

年代:1990

数据来源: WILEY

摘要:

AbstractAdjunct consideration of both qualitative (affection status) and quantitative (correlated liability indicator) information to define a bivariate phenotype can increase considerably the accuracy and efficiency of disease risk estimation. A general approach for calculating morbid risks to offspring on the basis of parental affection status and an offspring quantitative trait is presented. We also describe two different bivariate models of multifactorial inheritance, as implemented in the computer programs POINTER and YPOINT, and make explicit their assumptions/constraints when estimating the within‐person and parent–offspring correlations necessary for calculation of morbid risks. We use psychometric family data on schizophrenia from the New York High‐Risk Project to estimate these correlations and illustrate our methods. Our results show that even when a trait is only moderately correlated with liability, incorporation of quantitative trait information can lead to resolution of a range of risk to offspring that is not possible through reliance on parental affection status alone. Bivariate models provide a useful methodology for incorporating quantitative indicators of liability in the investigation of genetically complex dis

ISSN:0741-0395    

DOI:10.1002/gepi.1370070507

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

年代:1990

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370070508

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

年代:1990

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370070501

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

年代:1990

数据来源: WILEY