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Binary Traits (binary + trait)
Selected AbstractsA Likelihood-Based Trait-Model-Free Approach for Linkage Detection of Binary TraitBIOMETRICS, Issue 1 2010S. Basu Summary Trait-model-free (or "allele-sharing") approach to linkage analysis is a popular tool in genetic mapping of complex traits, because of the absence of explicit assumptions about the underlying mode of inheritance of the trait. The likelihood framework introduced by Kong and Cox (1997,,American Journal of Human Genetics,61, 1179,1188) allows calculation of accurate p-values and LOD scores to test for linkage between a genomic region and a trait. Their method relies on the specification of a model for the trait-dependent segregation of marker alleles at a genomic region linked to the trait. Here we propose a new such model that is motivated by the desire to extract as much information as possible from extended pedigrees containing data from individuals related over several generations. However, our model is also applicable to smaller pedigrees, and has some attractive features compared with existing models (Kong and Cox, 1997), including the fact that it incorporates information on both affected and unaffected individuals. We illustrate the proposed model on simulated and real data, and compare its performance with the existing approach (Kong and Cox, 1997). The proposed approach is implemented in the program lm_ibdtests within the framework of MORGAN 2.8 (http://www.stat.washington.edu/thompson/Genepi/MORGAN/Morgan.shtml). [source] Bivariate association analyses for the mixture of continuous and binary traits with the use of extended generalized estimating equationsGENETIC EPIDEMIOLOGY, Issue 3 2009Jianfeng Liu Abstract Genome-wide association (GWA) study is becoming a powerful tool in deciphering genetic basis of complex human diseases/traits. Currently, the univariate analysis is the most commonly used method to identify genes associated with a certain disease/phenotype under study. A major limitation with the univariate analysis is that it may not make use of the information of multiple correlated phenotypes, which are usually measured and collected in practical studies. The multivariate analysis has proven to be a powerful approach in linkage studies of complex diseases/traits, but it has received little attention in GWA. In this study, we aim to develop a bivariate analytical method for GWA study, which can be used for a complex situation in which continuous trait and a binary trait are measured under study. Based on the modified extended generalized estimating equation (EGEE) method we proposed herein, we assessed the performance of our bivariate analyses through extensive simulations as well as real data analyses. In the study, to develop an EGEE approach for bivariate genetic analyses, we combined two different generalized linear models corresponding to phenotypic variables using a seemingly unrelated regression model. The simulation results demonstrated that our EGEE-based bivariate analytical method outperforms univariate analyses in increasing statistical power under a variety of simulation scenarios. Notably, EGEE-based bivariate analyses have consistent advantages over univariate analyses whether or not there exists a phenotypic correlation between the two traits. Our study has practical importance, as one can always use multivariate analyses as a screening tool when multiple phenotypes are available, without extra costs of statistical power and false-positive rate. Analyses on empirical GWA data further affirm the advantages of our bivariate analytical method. Genet. Epidemiol. 2009. © 2008 Wiley-Liss, Inc. [source] QUANTITATIVE GENETICS OF SEXUAL PLASTICITY: THE ENVIRONMENTAL THRESHOLD MODEL AND GENOTYPE-BY-ENVIRONMENT INTERACTION FOR PHALLUS DEVELOPMENT IN THE SNAIL BULINUS TRUNCATUSEVOLUTION, Issue 5 2000Marie-France Ostrowski Abstract Sexual polymorphisms are model systems for analyzing the evolution of reproductive strategies. However, their plasticity and other binary traits have rarely been studied, with respect to environmental variables. A possible reason is that, although threshold models offer an adequate quantitative genetics framework for binary traits in a single environment, analyzing their plasticity requires more refined empirical and theoretical approaches. The statistical framework proposed here, based on the environmental threshold model (ETM), should partially fill this gap. This methodology is applied to an empirical dataset on a plastic sexual polymorphism, aphally, in the snail Bulinus truncatus. Aphally is characterized by the co-occurrence of regular hermaphrodites (euphallics) together with hermaphrodites deprived of the male copulatory organ (aphallics). Reaction norms were determined for 40 inbred lines, distributed at three temperatures, in a first experiment. A second experiment allowed us to rule out maternal effects. We confirmed the existence of high broad-sense heritabilities as well as a positive effect of high temperatures on aphally. However a significant genotype-by-environment interaction was detected for the first time, suggesting that sexual plasticity itself can respond to selection. A nested series of four ETM-like models was developed for estimating genetical effects on both mean aphally rate and plasticity. These models were tested using a maximum-likelihood procedure and fitted to aphally data. Although no perfect fit of models to data was observed, the refined versions of ETM models conveniently reduce the analysis of complex reaction norms of binary traits into standard quantitative genetics parameters, such as genetic values and environmental variances. [source] Bivariate association analyses for the mixture of continuous and binary traits with the use of extended generalized estimating equationsGENETIC EPIDEMIOLOGY, Issue 3 2009Jianfeng Liu Abstract Genome-wide association (GWA) study is becoming a powerful tool in deciphering genetic basis of complex human diseases/traits. Currently, the univariate analysis is the most commonly used method to identify genes associated with a certain disease/phenotype under study. A major limitation with the univariate analysis is that it may not make use of the information of multiple correlated phenotypes, which are usually measured and collected in practical studies. The multivariate analysis has proven to be a powerful approach in linkage studies of complex diseases/traits, but it has received little attention in GWA. In this study, we aim to develop a bivariate analytical method for GWA study, which can be used for a complex situation in which continuous trait and a binary trait are measured under study. Based on the modified extended generalized estimating equation (EGEE) method we proposed herein, we assessed the performance of our bivariate analyses through extensive simulations as well as real data analyses. In the study, to develop an EGEE approach for bivariate genetic analyses, we combined two different generalized linear models corresponding to phenotypic variables using a seemingly unrelated regression model. The simulation results demonstrated that our EGEE-based bivariate analytical method outperforms univariate analyses in increasing statistical power under a variety of simulation scenarios. Notably, EGEE-based bivariate analyses have consistent advantages over univariate analyses whether or not there exists a phenotypic correlation between the two traits. Our study has practical importance, as one can always use multivariate analyses as a screening tool when multiple phenotypes are available, without extra costs of statistical power and false-positive rate. Analyses on empirical GWA data further affirm the advantages of our bivariate analytical method. Genet. Epidemiol. 2009. © 2008 Wiley-Liss, Inc. [source] Testing association in the presence of linkage , a powerful score for binary traitsGENETIC EPIDEMIOLOGY, Issue 6 2007Gudrun Jonasdottir Abstract We present a score for testing association in the presence of linkage for binary traits. The score is robust to varying degrees of linkage, and it is valid under any ascertainment scheme based on trait values as well as under population stratification. The score test is derived from a mixed effects model where population level association is modeled using a fixed effect and where correlation among related individuals is allowed for by using log-gamma random effects. The score, as presented in this paper, does not assume full information about the inheritance pattern in families or parental genotypes. We compare the score to the semi-parametric family-based association test (FBAT), which has won ground because of its flexible and simple form. We show that a random effects formulation of co-inheritance can improve the power substantially. We apply the method to data from the Collaborative Study on the Genetics of Alcoholism. We compare our findings to previously published results. Genet. Epidemiol. 2007. © 2007 Wiley-Liss, Inc. [source] A Bayesian approach to the transmission/disequilibrium test for binary traitsGENETIC EPIDEMIOLOGY, Issue 1 2002Varghese George Abstract The transmission/disequilibrium test (TDT) for binary traits is a powerful method for detecting linkage between a marker locus and a trait locus in the presence of allelic association. The TDT uses information on the parent-to-offspring transmission status of the associated allele at the marker locus to assess linkage or association in the presence of the other, using one affected offspring from each set of parents. For testing for linkage in the presence of association, more than one offspring per family can be used. However, without incorporating the correlation structure among offspring, it is not possible to correctly assess the association in the presence of linkage. In this presentation, we propose a Bayesian TDT method as a complementary alternative to the classical approach. In the hypothesis testing setup, given two competing hypotheses, the Bayes factor can be used to weigh the evidence in favor of one of them, thus allowing us to decide between the two hypotheses using established criteria. We compare the proposed Bayesian TDT with a competing frequentist-testing method with respect to power and type I error validity. If we know the mode of inheritance of the disease, then the joint and marginal posterior distributions for the recombination fraction (,) and disequilibrium coefficient (,) can be obtained via standard MCMC methods, which lead naturally to Bayesian credible intervals for both parameters. Genet. Epidemiol. 22:41,51, 2002. © 2002 Wiley-Liss, Inc. [source] Generalized marker regression and interval QTL mapping methods for binary traits in half-sib family designsJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 5 2001H. N. Kadarmideen A Generalized Marker Regression Mapping (GMR) approach was developed for mapping Quantitative Trait Loci (QTL) affecting binary polygenic traits in a single-family half-sib design. The GMR is based on threshold-liability model theory and regression of offspring phenotype on expected marker genotypes at flanking marker loci. Using simulation, statistical power and bias of QTL mapping for binary traits by GMR was compared with full QTL interval mapping based on a threshold model (GIM) and with a linear marker regression mapping method (LMR). Empirical significance threshold values, power and estimates of QTL location and effect were identical for GIM and GMR when QTL mapping was restricted to within the marker interval. These results show that the theory of the marker regression method for QTL mapping is also applicable to binary traits and possibly for traits with other non-normal distributions. The linear and threshold models based on marker regression (LMR and GMR) also resulted in similar estimates and power for large progeny group sizes, indicating that LMR can be used for binary data for balanced designs with large families, as this method is computationally simpler than GMR. GMR may have a greater potential than LMR for QTL mapping for binary traits in complex situations such as QTL mapping with complex pedigrees, random models and models with interactions. Generalisierte Marker Regression und Intervall QTL Kartierungsmethoden für binäre Merkmale in einem Halbgeschwisterdesign Es wurde ein Ansatz zur generalisierten Marker Regressions Kartierung (GMR) entwickelt, um quantitative Merkmalsloci (QTL) zu kartieren, die binäre polygenetische Merkmale in einem Einfamilien-Halbgeschwisterdesign beeinflussen. Das GMR basiert auf der Theorie eines Schwellenwertmodells und auf der Regression des Nachkommenphänotyps auf den erwarteten Markergenotyp der flankierenden Markerloci. Mittels Simulation wurde die statistische Power und Schiefe der QTL Kartierung für binäre Merkmale nach GMR verglichen mit vollständiger QTL Intervallkartierung, die auf einem Schwellenmodell (GIM) basiert, und mit einer Methode zur linearen Marker Regressions Kartierung (LMR). Empirische Signifikanzschwellenwerte, Power und Schätzer für die QTL Lokation und der Effekt waren für GIM und GMR identisch, so lange die QTL Kartierung innerhalb des Markerintervalls definiert war. Diese Ergebnisse zeigen, dass die Theorie der Marker Regressions-Methode zur QTL Kartierung auch für binäre Merkmale und möglicherweise auch für Merkmale, die keiner Normalverteilung folgen, geeignet ist. Die linearen und Schwellenmodelle, die auf Marker Regression (LMR und GMR) basieren, ergaben ebenfalls ähnliche Schätzer und Power bei großen Nachkommengruppen, was schlussfolgern lässt, dass LMR für binäre Daten in einem balancierten Design mit großen Familien genutzt werden kann. Schließlich ist diese Methode computertechnisch einfacher als GMR. GMR mag für die QTL Kartierung bei binären Merkmalen in komplexen Situationen ein größeres Potential haben als LMR. Ein Beispiel dafür ist die QTL Kartierung mit komplexen Pedigrees, zufälligen Modellen und Interaktionsmodellen. [source] Quantifying Genomic Imprinting in the Presence of LinkageBIOMETRICS, Issue 4 2006Quentin Vincent Summary Genomic imprinting decreases the power of classical linkage analysis, in which paternal and maternal transmissions of marker alleles are equally weighted. Several methods have been proposed for taking genomic imprinting into account in the model-free linkage analysis of binary traits. However, none of these methods are suitable for the formal identification and quantification of genomic imprinting in the presence of linkage. In addition, the available methods are designed for use with pure sib-pairs, requiring artificial decomposition in cases of larger sibships, leading to a loss of power. We propose here the maximum likelihood binomial method adaptive for imprinting (MLB-I), which is a unified analytic framework giving rise to specific tests in sibships of any size for (i) linkage adaptive to imprinting, (ii) genomic imprinting in the presence of linkage, and (iii) partial versus complete genomic imprinting. In addition, we propose an original measure for quantifying genomic imprinting. We have derived and validated the distribution of the three tests under their respective null hypotheses for various genetic models, and have assessed the power of these tests in simulations. This method can readily be applied to genome-wide scanning, as illustrated here for leprosy sibships. Our approach provides a novel tool for dissecting genomic imprinting in model-free linkage analysis, and will be of considerable value for identifying and evaluating the contribution of imprinted genes to complex diseases. [source] | ||||||||||