摘要:

AbstractParticipants in the Alzheimer's disease component of GAW8 had access to three collections of pedigrees, complete with marker data from chromosomes 19 and 21. There were a total of 94 independent pedigrees and more than 2,000 individuals. Onset of the disorder varied widely among pedigrees. These data are briefly summarized along with a discussion of the problems associated with performing genetic analyses of Alzheimer's disease. The majority of the workshop participants performed an analysis either with some of the data contributed to the workshop or with data simulated on pedigrees of the same structure and disease status as were contributed. There were also a few purely methodological contributions. The contributions are summarized in three general areas: family association and phenotype, linkage analysis, and heterogeneity tests. © 1993 Wiley‐Liss, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370100604

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

年代:1993

数据来源: WILEY

摘要:

AbstractFamilial Alzheimer disease is a neurological disorder of adult onset. Three research centers have each contributed their families and genetic linkage data for combined analyses. The data from the Duke and Boston centers, comprising 73 pedigrees for whom numerous markers on chromosomes 19 and 21 were typed, are described. © 1993 Wiley‐Liss, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370100605

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

年代:1993

数据来源: WILEY

摘要:

AbstractForty families submitted to Genetic Analysis Workshop 8 are described. These are the families in the Seattle data set which have been typed for at least one genetic marker from the centromeric region of chromosome 21 or the q arm of chromosome 19. Thirteen of these families have average ages of onset below age 61 and are therefore considered to be early onset families. Seven of the families are of Volga German descent. Thirty‐four of the families have autopsy documented Alzheimer's disease, including all 13 of the early onset pedigrees. The data set includes both the clinical and pedigree information available on the portions of the pedigrees used in the linkage analyses, genotype data on three loci on chromosome 19 and four loci on chromosome 21, and more extended family data on individuals who have not been included in the linkage analyses. © 1993 Wiley‐Liss,

ISSN:0741-0395    

DOI:10.1002/gepi.1370100606

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

年代:1993

数据来源: WILEY

摘要:

AbstractSib‐pair linkage analyses were used to search for linkage to a set of chromosome 19 and 21 marker loci in two sets of families with Alzheimer's disease. The advantage of this technique is that no assumption is made about the mode of inheritance of the disease. Some mild suggestions of linkage were found in early‐onset families for a chromosome 21 marker and in a set of late‐onset families for a chromosome 19 marker. © 1993 Wiley‐L

ISSN:0741-0395    

DOI:10.1002/gepi.1370100607

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

年代:1993

数据来源: WILEY

摘要:

AbstractFour relative‐pair methods for detecting genetic linkage were applied to familial Alzheimer's disease data. Results obtained using an extended Haseman‐Elston test and a weighted rank pairwise correlation test, which both use information from all relative pairs, were consistent with previously published likelihood results and appear to be more powerful than affected sib pair methods. © 1993 Wiley‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370100608

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe multipoint identity‐by‐descent method was developed to detect linkage to a specific chromosomal region through partitioning the genetic variance. This method has previously been applied to quantitative traits, and here is extended to a qualitative trait, where a dichotomous affected/unaffected status variable is transformed to a quantitative variable by incorporating covariates. This method is applied to the Alzheimer's disease data sets from Genetic Analysis Workshop 8, to investigate putative linkage to chromosomes 19 and 21. The multipoint identity‐by‐descent method is used to test for linkage through the qualitative trait, and for excess sharing of the chromosomal region among affected sibs. Results are compared to those of the affected‐pedigree‐member method and classical linkage analysis. None of these methods gave results showing clear linkage, with the only marginally significant results occurring for the Boston data set on chromosome 19 and the Duke data set for chromosome 21 using the multipoint identity‐by‐descent method. © 1993

ISSN:0741-0395    

DOI:10.1002/gepi.1370100609

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe show that the null hypothesis in the Affected‐Pedigree‐Member (APM) method is composed of two sub‐hypotheses: no linkage and correct marker allele distribution. As a result, the APM method is not robust to misspecification of marker allele frequencies. © 1993 Wiley‐L

ISSN:0741-0395    

DOI:10.1002/gepi.1370100610

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe evidence for linkage between Alzheimer's disease and markers on both chromosomes 19 and 21 [Pericak‐Vance et al., 1991] by the affected‐pedigree‐member (APM) method [Weeks and Lange, 1988]cannot be replicated on any of the available GAW8 data sets when marker allele frequencies are estimated from the combined sample. The strong dependence of the APM method on accurate estimation of marker allele frequencies, and the effects of noninformative pairs and of genetic distance in informative pairs of relatives are illustrated. © 1993 Wiley‐L

ISSN:0741-0395    

DOI:10.1002/gepi.1370100611

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe have developed a novel test of heterogeneity based on the APM method. We present tests of this method on both empiric and simulated data. © 1993 Wiley‐Liss, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370100612

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe two‐point lod score linkage analysis of familial Alzheimer's disease is sensitive to the parameters of age‐dependent penetrance rate, phenocopy rate, heterogeneity, and marker gene frequency. If unsuitable parameters are used, it may lead to false negative evidence against linkage. However, it is clear that, in some cases, it may lead to false positive evidence of linkage. © 1993 Wiley‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370100613

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

年代:1993

数据来源: WILEY