A framework for analyzing both linkage and association: an analysis of Genetic Analysis Workshop 16 simulated data
نویسندگان
چکیده
We examine a Bayesian Markov-chain Monte Carlo framework for simultaneous segregation and linkage analysis in the simulated single-nucleotide polymorphism data provided for Genetic Analysis Workshop 16. We conducted linkage only, linkage and association, and association only tests under this framework. We also compared these results with variance-component linkage analysis and regression analyses. The results indicate that the method shows some promise, but finding genes that have very small (<0.1%) contributions to trait variance may require additional sources of information. All methods examined fared poorly for the smallest in the simulated "polygene" range (h2 of 0.0015 to 0.0002).
منابع مشابه
Two-stage study designs for analyzing disease-associated covariates: linkage thresholds and case-selection strategies
The incorporation of disease-associated covariates into studies aiming to identify susceptibility genes for complex human traits is a challenging problem. Accounting for such covariates in genetic linkage and association analyses may help reduce the genetic heterogeneity inherent in these complex phenotypes. For Genetic Analysis Workshop 15 (GAW15) Problem 3 simulated data, our goal was to comp...
متن کاملIdentifying causal rare variants of disease through family-based analysis of Genetics Analysis Workshop 17 data set
Linkage- and association-based methods have been proposed for mapping disease-causing rare variants. Based on the family information provided in the Genetic Analysis Workshop 17 data set, we formulate a two-pronged approach that combines both methods. Using the identity-by-descent information provided for eight extended pedigrees (n = 697) and the simulated quantitative trait Q1, we explore var...
متن کاملAn ordered subset approach to including covariates in the transmission disequilibrium test
Clinical heterogeneity of a disease may reflect an underlying genetic heterogeneity, which may hinder the detection of trait loci. Consequently, many statistical methods have been developed that allow for the detection of linkage and/or association signals in the presence of heterogeneity.This report describes the work of two parallel investigations into similar approaches to ordered subset ana...
متن کاملJoint linkage and association analysis for identification of potentially causal polymorphisms in GAW15 data
In a small chromosomal region, a number of polymorphisms may be both linked to and associated with a disease. Potentially directly associated causal loci may be distinguished from indirectly associated loci by determining which associations can explain the observed linkage signal. We apply methods for testing whether association with a particular polymorphism or haplotype can explain an observe...
متن کاملLinkage, case-control association, and family-based association tests for complex disorders
We carried out an analysis of the Genetic Analysis Workshop 15 simulated Problem 3 data. We restricted ourselves to the present/absent phenotype. Linkage analysis revealed a very strong signal on chromosome 6. Association analysis revealed additional susceptible loci located on chromosomes 11 and 18. The latter two signals were subsequently verified with linkage analysis - but only after 20 rep...
متن کامل