Bayesian Model Search and Multilevel Inference for Snp Association Studies.
نویسندگان
چکیده
Technological advances in genotyping have given rise to hypothesis-based association studies of increasing scope. As a result, the scientific hypotheses addressed by these studies have become more complex and more difficult to address using existing analytic methodologies. Obstacles to analysis include inference in the face of multiple comparisons, complications arising from correlations among the SNPs (single nucleotide polymorphisms), choice of their genetic parametrization and missing data. In this paper we present an efficient Bayesian model search strategy that searches over the space of genetic markers and their genetic parametrization. The resulting method for Multilevel Inference of SNP Associations, MISA, allows computation of multilevel posterior probabilities and Bayes factors at the global, gene and SNP level, with the prior distribution on SNP inclusion in the model providing an intrinsic multiplicity correction. We use simulated data sets to characterize MISA's statistical power, and show that MISA has higher power to detect association than standard procedures. Using data from the North Carolina Ovarian Cancer Study (NCOCS), MISA identifies variants that were not identified by standard methods and have been externally "validated" in independent studies. We examine sensitivity of the NCOCS results to prior choice and method for imputing missing data. MISA is available in an R package on CRAN.
منابع مشابه
Bayesian Model Search and Multilevel Inference for Snp Association Studies by Melanie
Technological advances in genotyping have given rise to hypothesisbased association studies of increasing scope. As a result, the scientific hypotheses addressed by these studies have become more complex and more difficult to address using existing analytic methodologies. Obstacles to analysis include inference in the face of multiple comparisons, complications arising from correlations among t...
متن کاملSingle Nucleotide Polymorphisms and Association Studies: A Few Critical Points
Uncovering DNA sequence variations that correlate with phenotypic changes, e.g., diseases, is the aim of sequence variation studies. Common types sequence variations are Single nucleotide polymorphism (SNP, pronounced snip).SNPs are the third-generation molecular marker. SNP represents a DNA sequence variant of a single base pair with the minor allele occurring in more than 1% of a given popula...
متن کاملInference from genome-wide association studies using a novel Markov model.
In this paper we propose a Bayesian modeling approach to the analysis of genome-wide association studies based on single nucleotide polymorphism (SNP) data. Our latent seed model combines various aspects of k-means clustering, hidden Markov models (HMMs) and logistic regression into a fully Bayesian model. It is fitted using the Markov chain Monte Carlo stochastic simulation method, with Metrop...
متن کاملBayesian Inference for Spatial Beta Generalized Linear Mixed Models
In some applications, the response variable assumes values in the unit interval. The standard linear regression model is not appropriate for modelling this type of data because the normality assumption is not met. Alternatively, the beta regression model has been introduced to analyze such observations. A beta distribution represents a flexible density family on (0, 1) interval that covers symm...
متن کاملA Surface Water Evaporation Estimation Model Using Bayesian Belief Networks with an Application to the Persian Gulf
Evaporation phenomena is a effective climate component on water resources management and has special importance in agriculture. In this paper, Bayesian belief networks (BBNs) as a non-linear modeling technique provide an evaporation estimation method under uncertainty. As a case study, we estimated the surface water evaporation of the Persian Gulf and worked with a dataset of observations ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The annals of applied statistics
دوره 4 3 شماره
صفحات -
تاریخ انتشار 2010