Abstract:
:The availability of high-density haplotype data has motivated several fine-scale linkage disequilibrium mapping methods for locating disease-causing mutations. These methods identify loci around which haplotypes of case chromosomes exhibit greater similarity than do those of control chromosomes. A difficulty arising in such mapping is the possibility that case chromosomes have inherited disease-causing mutations from different ancestral chromosomes (founder heterogeneity). Such heterogeneity dilutes measures of case haplotype similarity. This dilution can be mitigated by separating case chromosomes into subsets according to their putative mutation origin, and searching for an area with excessive haplotype similarity within each subset. We propose a nonparametric method for identifying subsets of case chromosomes likely to share a common ancestral progenitor. By simulation studies and application to published data, we show that the method accurately identifies relatively large subsets of chromosomes that share a common founder. We also show that the method allows more precise estimates of the disease mutation loci than obtained by other fine-scale mapping methods.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Yu K,Martin RB,Whittemore ASdoi
10.1002/gepi.20016subject
Has Abstractpub_date
2004-11-01 00:00:00pages
173-81issue
3eissn
0741-0395issn
1098-2272journal_volume
27pub_type
杂志文章abstract::This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently developed statistica...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.10304
更新日期:2004-04-01 00:00:00
abstract::DNA methylation is an important epigenetic mechanism that has been linked to complex diseases and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome-wide association studies, issues such as popu...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21789
更新日期:2014-04-01 00:00:00
abstract::For the association analysis of whole-genome sequencing (WGS) studies, we propose an efficient and fast spatial-clustering algorithm. Compared to existing analysis approaches for WGS data, that define the tested regions either by sliding or consecutive windows of fixed sizes along variants, a meaningful grouping of ne...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22040
更新日期:2017-05-01 00:00:00
abstract::A genome-wide correlation analysis and cluster analysis were utilized to determine chromosomal regions that had similar nonparametric linkage scores across families in order to locate interacting susceptibility loci for asthma. Conditional analysis was performed to detect any increase in lod score over baseline. Eight...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s266
更新日期:2001-01-01 00:00:00
abstract::With challenges in data harmonization and environmental heterogeneity across various data sources, meta-analysis of gene-environment interaction studies can often involve subtle statistical issues. In this paper, we study the effect of environmental covariate heterogeneity (within and between cohorts) on two approache...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21810
更新日期:2014-07-01 00:00:00
abstract::A major locus that determines levels of apolipoprotein B (apoB) was revealed by likelihood analysis on 331 members of 36 pedigrees. The major locus explained 43.2% of the observed variance, with the remainder attributed to random environmental factors. Estimated mean apoB levels (mg/dl) were 110.5 +/- 2.5, 141.9 +/- 4...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370040202
更新日期:1987-01-01 00:00:00
abstract::We analyzed the GAW11 data on alcoholism provided by the Collaborative Study on the Genetics of Alcoholism (COGA) using an extension of a new test of linkage and association for quantitative traits developed by George et al. [1999]. This method determines linkage between marker loci and quantitative traits, when allel...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370170758
更新日期:1999-01-01 00:00:00
abstract::Gene-gene interaction is believed to play an important role in understanding complex traits. Multifactor dimensionality reduction (MDR) was proposed by Ritchie et al. [2001. Am J Hum Genet 69:138-147] to identify multiple loci that simultaneously affect disease susceptibility. Although the MDR method has been widely u...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20416
更新日期:2009-11-01 00:00:00
abstract::Genetic Analysis Workshop 17 (GAW17) focused on the transition from genome-wide association study designs and methods to the study designs and statistical genetic methods that will be required for the analysis of next-generation sequence data including both common and rare sequence variants. In the 166 contributions t...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20659
更新日期:2011-01-01 00:00:00
abstract::In traits suspected to be governed by at least two loci, linkage analysis incorporating the joint action of both loci may improve the power to detect linkage, increase the precision of estimating locus positions and provide insight into the underlying etiological mechanism. Recently, we mapped two susceptibility loci ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20190
更新日期:2007-01-01 00:00:00
abstract::The aim of this paper is to generalize permutation methods for multiple testing adjustment of significant partial regression coefficients in a linear regression model used for microarray data. Using a permutation method outlined by Anderson and Legendre [1999] and the permutation P-value adjustment from Simon et al. [...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20255
更新日期:2008-01-01 00:00:00
abstract::In this paper we investigate the power to identify gene x gene interactions in genome-wide association studies. In our analysis we focus on two-stage analyses: analyses in which we only test for interactions between single nucleotide polymorphisms that show some marginal effect. We give two algorithms to compute signi...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20300
更新日期:2008-04-01 00:00:00
abstract::Due to the drop in sequencing cost, the number of sequenced genomes is increasing rapidly. To improve power of rare-variant tests, these sequenced samples could be used as external control samples in addition to control samples from the study itself. However, when using external controls, possible batch effects due to...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22057
更新日期:2017-11-01 00:00:00
abstract::The potential of genome-wide association analysis can only be realized when they have power to detect signals despite the detrimental effect of multiple testing on power. We develop a weighted multiple testing procedure that facilitates the input of prior information in the form of groupings of tests. For each group a...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20237
更新日期:2007-11-01 00:00:00
abstract::We contrast the pooling of multiple data sets with the compound HLOD (HLOD-C) and the posterior probability of linkage (PPL), two approaches that have been shown to have more power in the presence of genetic heterogeneity. We also propose and evaluate several multipoint extensions. ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s67
更新日期:2001-01-01 00:00:00
abstract::Haplotype sharing analysis is a well-established option for the investigation of the etiology of complex diseases. The statistical power of haplotype association methods depends strongly on how the information of unobserved haplotypes can be captured by multilocus genotypes. In this study we combine an entropy-based m...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20491
更新日期:2010-05-01 00:00:00
abstract::We have used the unblinded MG1/Q1 Genetic Analysis Workshop 12 simulated data as a model system for investigating the use of linkage disequilibrium structure and simple genotype-phenotype associations to identify candidate functional mutations within a gene of interest. Analysis of the pattern of pairwise linkage dise...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s620
更新日期:2001-01-01 00:00:00
abstract::The results of classical segregation analysis on 159 families with polycystic kidney disease (PKD) are presented. It had been previously estimated that about 95% of autosomal dominant PKD (ADPKD) families have PKD1, the gene localized to chromosome 16p. The main purpose of the study was to determine if PKD shows any s...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370100305
更新日期:1993-01-01 00:00:00
abstract::Path analysis of nuclear family data has been widely applied to resolve genetic and environmental sources of familial resemblance. Here we report the results of a systematic evaluation of the effects of departures from five modeling assumptions often made when analyzing nuclear family data; i) the observed environment...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370060207
更新日期:1989-01-01 00:00:00
abstract::Increasing evidence has shown that genes may cause prenatal, neonatal, and pediatric diseases depending on their parental origins. Statistical models that incorporate parent-of-origin effects (POEs) can improve the power of detecting disease-associated genes and help explain the missing heritability of diseases. In ma...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22060
更新日期:2017-11-01 00:00:00
abstract::Simulation studies were conducted to assess to what extent the conclusions of segregation analysis, performed under the unified model, can be affected by the presence of unmeasured environmental factors shared by family members. Dichotomous data were generated on six-member nuclear families under two variants of the m...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370060140
更新日期:1989-01-01 00:00:00
abstract::We have conducted a study of renal sodium and potassium reabsorption in 205 pairs of twins on freely chosen diets; 89 of the subjects were studied on more than one occasion. Renal tubular sodium and potassium handling, as measured by the fractional excretions FENa and FEK, show repeatable differences between individua...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370020103
更新日期:1985-01-01 00:00:00
abstract::The restricted partition method (RPM) is a partitioning algorithm for examining multi-locus genotypes as (potentially non-additive) predictors of a quantitative trait. The motivating application was to develop a robust method to examine quantitative phenotypes for epistasis (gene-gene interactions), but the method can...
journal_title:Genetic epidemiology
pub_type: 杂志文章,评审
doi:10.1002/gepi.20006
更新日期:2004-09-01 00:00:00
abstract::The potential importance of the joint action of genes, whether modeled with or without a statistical interaction term, has long been recognized. However, identifying such action has been a great challenge, especially when millions of genetic markers are involved. We propose a likelihood ratio-based Mann-Whitney test t...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21651
更新日期:2012-09-01 00:00:00
abstract::A recently developed nonparametric method is a generalization of the transmission disequilibrium test across all alleles of a locus. This approach has been applied to Problem 2 of GAW10 and has been extended to explore the combined contribution of neighboring loci for chromosomes 1, 5, and 8. When applied to the chrom...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:6<857::AID-GEPI49>
更新日期:1997-01-01 00:00:00
abstract::HLA-A, -B, -C, -DR, and -DQ typings of the Schmiedeleut Hutterites of South Dakota were collected as part of an ongoing genetic-epidemiologic study of HLA and fertility. A total of 1,082 individuals, including 852 married adults representative of the reproductive population of this isolate, were characterized for five...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120106
更新日期:1995-01-01 00:00:00
abstract::It is believed that interactions among genes (epistasis) may play an important role in susceptibility to common diseases (Moore and Williams [2002]. Ann Med 34:88-95; Ritchie et al. [2001]. Am J Hum Genet 69:138-147). To study the underlying genetic variants of diseases, genome-wide association studies (GWAS) that sim...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20514
更新日期:2010-09-01 00:00:00
abstract::Bone mass may be so reduced in some individuals as to be characterized as osteoporotic, with resulting fracture, particularly of the proximal femur, vertebrae, or wrist. We identified 34 mother-daughter sets (n = 70) and 29 sibling sets (n = 59) from a community study of bone mass correlates to assess the degree of re...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370030204
更新日期:1986-01-01 00:00:00
abstract::Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian li...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/1098-2272(2000)19:1+<::AID-GEPI8>3.0.CO;2-
更新日期:2000-01-01 00:00:00
abstract::Association tests of multilocus haplotypes are of interest both in linkage disequilibrium mapping and in candidate gene studies. For case-parent trios, I discuss the extension of existing multilocus methods to include ambiguous haplotypes in tests of models which distinguish between the cis and trans phase. A likeliho...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.10252
更新日期:2003-09-01 00:00:00