摘要:

AbstractProblem 1 consisted of artificial data simulated from an oligogenic (four‐locus) disease model. The data set contained 200 nuclear families with at least one affected child and 100 control families with no affected members. Two of the disease loci were intended to be detectable via association analysis but not necessarily via linkage analysis, and the other two were virtually undetectable in this data set. Participants used association analysis, linkage analysis, and segregation analysis to analyze these data. Their findings are summarized, and analysis strategies are discussed. ©1995 Wiley‐Liss,

ISSN:0741-0395    

DOI:10.1002/gepi.1370120604

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

年代:1995

数据来源: WILEY

摘要:

AbstractProblem 1 was designed to involve an oligogenic model with four “disease susceptibility” loci, such that all individuals with at least four “upper‐case” alleles were at equal risk to be affected (and those with three or fewer were not at risk). Two of these loci were identical to marker loci, thus giving rise to weak disease‐marker associations. The other two were located between marker loci, with no linkage disequilibrium. Participants were given 200 nuclear families with at least one affected child, along with 100 control families with no affected individuals. The first two loci were intended to be detectable via association analysis. The remaining two loci were virtually undetectable in this data set. ©1995 Wil

ISSN:0741-0395    

DOI:10.1002/gepi.1370120605

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

年代:1995

数据来源: WILEY

摘要:

AbstractHerein we describe the methods utilized to simulate the genetic marker data for GAW9 Problems 1 and 2, as well as the pedigree and phenotype data for GAW9 Problem 1. ©1995 Wiley‐Liss, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370120606

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

年代:1995

数据来源: WILEY

摘要:

AbstractSibling risk ratios are used to quantify the genetic effect of two simulated disease loci, identified through TDT and association methods and characterized via components of variance derived from a relative penetrance matrix. Inconsistencies between the data set and the simulating model are also discussed. ©1995 Wiley‐Liss, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370120607

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

年代:1995

数据来源: WILEY

摘要:

AbstractModel‐free methods of testing for association of a disease with alleles at a marker locus were used to analyze simulated data for a rare disease locus and 360 marker loci distributed at 2 cM intervals along six chromosomes. After adjustment for multiple tests, there was no evidence of significant heterogeneity of parental allele frequencies between a sample of parents with at least one affected child and a sample of parents with no affected children. Several significant deviations from Hardy‐Weinberg equilibrium were detected after Bonferroni correction but these were Type I errors. After adjusting for multiple tests, the model‐free test for association detected significant associations of alleles at two loci with the disease. These associations were in fact part of the generating model for the simulated data. However, these methods were unable to detect two other major loci contributing to the disease since these loci were not associated with any of the marker loci. ©1995 Wiley‐L

ISSN:0741-0395    

DOI:10.1002/gepi.1370120608

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

年代:1995

数据来源: WILEY

摘要:

AbstractSusceptibility genes are identified for a simulated complex trait by a systematic genome search for linkage between disease and a genetic marker in the presence of gametic disequilibrium. The transmission/disequilibrium tests TDTaor TDTgfor multiallelic markers compare transmitted and nontransmitted alleles or the genotypes formed by the two transmitted alleles and the genotypes formed by the two nontransmitted alleles, respectively. With these two tests we were able to identify the two markers D1G31 and D5G23. Under the simulating model these are in fact two susceptibility genes involved in the disease. ©1995 Wiley‐Liss, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370120609

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe aim of this study is to compare the power of the transmission disequilibrium test (TDT) to that of the identity‐by‐descent (IBD) distribution test. The relative powers of these tests depend both on the underlying genetic model and on the available family data. Families with two affected sibs are always more informative than those with one affected child and one unaffected child. The IBD test is always more powerful in the first situation and, contrary to the TDT, is independent of the presence of gametic disequilibrium. When there is strong linkage disequilibrium, the TDT can be more powerful than the IBD test. In that case, linkage can be detected by the TDT even in families with only one affected child. ©1995 Wiley‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370120610

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

年代:1995

数据来源: WILEY

摘要:

AbstractTwo susceptibility genes, in linkage disequilibrium with alleles of the markers D1G31 and D5G23, have been identified for the disease in the simulated data set of Problem 1. Here we apply the MASC (marker association segregation chi‐square) method to model the joint effect of these two genes, by testing two‐locus models. The model we obtain, that is the most parsimonious and that best fits the data, corresponds to a direct involvement of the alleles D1G31‐8 and D5G23‐7, with a nonmultiplicative effect of the two alleles. This was indeed assumed in the true model used for simulating the data. ©1995 Wiley

ISSN:0741-0395    

DOI:10.1002/gepi.1370120611

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

年代:1995

数据来源: WILEY

摘要:

AbstractIn this paper, we explore the use of a variety of familial transmission tests (and case‐control analyses) to screen for allelic associations in simulated marker data of a quality (2 cM map) that will feasibly arise from genomic scans within the next 5‐10 years. We demonstrate a form of the transmission‐disequilibrium test extended to multiallele systems. The methods used were log‐linear and related models implemented largely using standard statistical packages. ©1995 Wiley

ISSN:0741-0395    

DOI:10.1002/gepi.1370120612

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe set out to apply conventional analytic methods to a GAW data set of nuclear families with an oligogenic disease that has a population prevalence of 0.023. We chose methods generally applied to disorders with at least one major gene. Our approaches included: (1) complex segregation analysis under two models of ascertainment, (2) linkage analysis assuming either a single‐locus trait with possible genetic heterogeneity or a two‐locus trait, and (3) allelic association studies using both a case/control approach and the haplotype relative risk (HRR) test. The association study was the only analysis of the three that provided evidence for genes playing a role in the etiology of this disorder. ©1995 Wiley‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370120613

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

年代:1995

数据来源: WILEY