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Genetic investigations often involve the testing of vast numbers of related hypotheses simultaneously. To control the overall error rate, a substantial penalty is required, making it difficult to detect signals of moderate strength. To…

Methodology · Statistics 2010-10-25 Kathryn Roeder , Larry Wasserman

Dermatological diseases pose a major threat to the global health, affecting almost one-third of the world's population. Various studies have demonstrated that early diagnosis and intervention are often critical to prognosis and outcome. To…

Computer Vision and Pattern Recognition · Computer Science 2022-08-25 Gelei Xu , Yawen Wu , Jingtong Hu , Yiyu Shi

We introduce a method for computation of exact conditional efficiency robust enumeration p-values for detection of genotype--phenotype associations at a single bi-allelic genetic locus. Our method can be based on any arbitrary ranking test…

Methodology · Statistics 2015-05-14 Max Moldovan , Mette Langaas

We propose a general and formal statistical framework for multiple tests of association between known fixed features of a genome and unknown parameters of the distribution of variable features of this genome in a population of interest. The…

Applications · Statistics 2008-12-18 Sandrine Dudoit , Sündüz Keleş , Mark J. van der Laan

Based on the normal distribution and its properties, i.e., average and variance, Fisher works have provided a conceptual framework to identify genotype-phenotype associations. While Fisher intuition has proved fruitful over the past…

Populations and Evolution · Quantitative Biology 2023-07-06 Cyril Rauch , Panagiota Kyratzi , Andras Paldi

In genetic association studies, a single marker is often associated with multiple, correlated phenotypes (e.g., obesity and cardiovascular disease, or nicotine dependence and lung cancer). A pervasive question is then whether that marker…

Conventional multiple testing procedures often assume hypotheses for different features are exchangeable. However, in many scientific applications, additional covariate information regarding the patterns of signals and nulls are available.…

Methodology · Statistics 2020-06-12 Xianyang Zhang , Jun Chen

Motivated by genetic association studies of pleiotropy, we propose here a Bayesian latent variable approach to jointly study multiple outcomes or phenotypes. The proposed method models both continuous and binary phenotypes, and it accounts…

Applications · Statistics 2012-11-08 Lizhen Xu , Radu V. Craiu , Lei Sun

We consider the problem of multiple hypothesis testing with generic side information: for each hypothesis $H_i$ we observe both a p-value $p_i$ and some predictor $x_i$ encoding contextual information about the hypothesis. For large-scale…

Methodology · Statistics 2018-07-26 Lihua Lei , William Fithian

We introduce a novel class of factor analysis methodologies for the joint analysis of multiple studies. The goal is to separately identify and estimate 1) common factors shared across multiple studies, and 2) study-specific factors. We…

Applications · Statistics 2018-06-27 Roberta De Vito , Ruggero Bellio , Lorenzo Trippa , Giovanni Parmigiani

For testing a group of hypotheses, tremendous $p$-value combination methods have been developed and widely applied since 1930's. Some methods (e.g., the minimal $p$-value) are optimal for sparse signals, and some others (e.g., Fisher's…

Methodology · Statistics 2018-01-16 Hong Zhang , Tiejun Tong , John E Landers , Zheyang Wu

In this article, we propose a covariance based method for combining partial data sets in the genotype to phenotype spectrum. In particular, an expectation-maximization algorithm that can be used to combine partially overlapping…

Applications · Statistics 2020-01-13 Deniz Akdemir , Julio Isidro Sanchez

Genome-wide association studies (GWAS) have identified hundreds of loci at very stringent levels of statistical significance across many different human traits. However, it is now clear that very large samples (n~10^4-10^5) are needed to…

Genomics · Quantitative Biology 2013-08-20 Inti Pedroso

In the search for genetic factors that are associated with complex heritable human traits, considerable attention is now being focused on rare variants that individually have small effects. In response, numerous recent papers have proposed…

Methodology · Statistics 2014-09-10 Andriy Derkach , Jerry F. Lawless , Lei Sun

Many common diseases are highly polygenic, modulated by a large number genetic factors with small effects on susceptibility to disease. These small effects are difficult to map reliably in genetic association studies. To address this…

Quantitative Methods · Quantitative Biology 2012-08-23 Peter Carbonetto , Matthew Stephens

Recent genome-wide association studies (GWAS) have been successful in identifying associations between genetic variants and simple cardiac parameters derived from cardiac magnetic resonance (CMR) images. However, the emergence of big…

Large-scale multiple testing tasks often exhibit dependence, and leveraging the dependence between individual tests is still one challenging and important problem in statistics. With recent advances in graphical models, it is feasible to…

Methodology · Statistics 2012-10-19 Jie Liu , Chunming Zhang , Catherine McCarty , Peggy Peissig , Elizabeth Burnside , David Page

Genomic phenotypes, such as DNA methylation and chromatin accessibility, can be used to characterize the transcriptional and regulatory activity of DNA within a cell. Recent technological advances have made it possible to measure such…

Methodology · Statistics 2016-11-15 Jean Morrison , Noah Simon , Daniela Witten

Hypertension is a heterogeneous syndrome in need of improved subtyping using phenotypic and genetic measurements so that patients in different subtypes share similar pathophysiologic mechanisms and respond more uniformly to targeted…

Quantitative Methods · Quantitative Biology 2018-05-22 Yuan Luo , Chengsheng Mao , Yiben Yang , Fei Wang , Faraz S. Ahmad , Donna Arnett , Marguerite R. Irvin , Sanjiv J. Shah

In several modern applications, ranging from genetics to genomics and neuroimaging, there is a need to compare observations across different populations, such as groups of healthy and diseased individuals. The interest is in detecting a…

Methodology · Statistics 2012-05-14 Christopher Minas , Giovanni Montana
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