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Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and…

Methodology · Statistics 2025-08-18 Changshuai Wei , Robert C. Elston , Qing Lu

Sequencing-based studies are emerging as a major tool for genetic association studies of complex diseases. These studies pose great challenges to the traditional statistical methods (e.g., single-locus analyses based on regression methods)…

Methodology · Statistics 2025-08-18 Changshuai Wei , Qing Lu

Understanding how genetic variants influence cellular-level processes is an important step towards understanding how they influence important organismal-level traits, or "phenotypes", including human disease susceptibility. To this end…

Methodology · Statistics 2013-07-30 Heejung Shim , Matthew Stephens

With the advance of high-throughput sequencing technologies, it has become feasible to investigate the influence of the entire spectrum of sequencing variations on complex human diseases. Although association studies utilizing the new…

Methodology · Statistics 2025-08-19 Ming Li , Zihuai He , Min Zhang , Xiaowei Zhan , Changshuai Wei , Robert C Elston , Qing Lu

Advancement in sequencing technology enables the study of association between complex disorders and rare variants with low minor allele frequencies. One of the major challenges in rare variant testing is lack of statistical power of…

Quantitative Methods · Quantitative Biology 2016-07-27 Rui Sun , Haoyi Weng , Inchi Hu , Junfeng Guo , William K. K. Wu , Benny Chung-Ying Zee , Maggie Haitian Wang

While progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain…

Applications · Statistics 2025-08-18 Olga A. Vsevolozhskaya , Dmitri V. Zaykin , Mark C. Greenwood , Changshuai Wei , Qing Lu

Global expression analyses using microarray technologies are becoming more common in genomic research, therefore, new statistical challenges associated with combining information from multiple studies must be addressed. In this paper we…

Applications · Statistics 2013-01-29 Jia Li , George C. Tseng

The development of next generation sequencing (NGS) technology and genotype imputation methods enabled researchers to measure both common and rare variants in genome-wide association studies (GWAS). Statistical methods have been proposed to…

Methodology · Statistics 2018-12-14 XIaoyu Cai , Lo-Bin Chang , Chi Song

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

Historically, the majority of statistical association methods have been designed assuming availability of SNP-level information. However, modern genetic and sequencing data present new challenges to access and sharing of genotype-phenotype…

Genomics · Quantitative Biology 2020-07-01 Olga A Vsevolozhskaya , Min Shi , Fengjiao Hu , Dmitri V Zaykin

Second generation sequencing technologies are being increasingly used for genetic association studies, where the main research interest is to identify sets of genetic variants that contribute to various phenotype. The phenotype can be…

Methodology · Statistics 2025-08-18 Changshuai Wei , Qing Lu

Genetic association studies, in particular the genome-wide association study design, have provided a wealth of novel insights into the aetiology of a wide range of human diseases and traits. The next challenge consists of understanding the…

Gene-based testing is a commonly employed strategy in many genetic association studies. Gene-trait associations can be complex due to underlying population heterogeneity, gene-environment interactions, and various other reasons. Existing…

Methodology · Statistics 2020-12-15 Tianying Wang , Iuliana Ionita-Laza , Ying Wei

High-dimensional phenotypes hold promise for richer findings in association studies, but testing of several phenotype traits aggravates the grand challenge of association studies, that of multiple testing. Several methods have recently been…

Methodology · Statistics 2013-05-14 Pekka Marttinen , Jussi Gillberg , Aki Havulinna , Jukka Corander , Samuel Kaski

Variations in complex traits are influenced by multiple genetic variants, environmental risk factors, and their interactions. Though substantial progress has been made in identifying single genetic variants associated with complex traits,…

Genomics · Quantitative Biology 2025-08-22 Ming Li , Ruo-Sin Peng , Changshuai Wei , Qing Lu

Genetic association study is an essential step to discover genetic factors that are associated with a complex trait of interest. In this paper we present a novel generalized quasi-likelihood score (GQLS) test that is suitable for a study…

Applications · Statistics 2011-11-24 Zeny Feng , William W. L. Wong , Xin Gao , Flavio Schenkel

We consider the problems of hypothesis testing and model comparison under a flexible Bayesian linear regression model whose formulation is closely connected with the linear mixed effect model and the parametric models for SNP set analysis…

Methodology · Statistics 2015-02-24 Xiaoquan Wen

Because of the recent advances of genome sequences, a large number of human genome sequences are available for the study of human genetics. Genome-wide association studies typically focus on associations between single-nucleotide…

Populations and Evolution · Quantitative Biology 2019-10-11 Kazuharu Misawa

2 Diabetes is a leading worldwide public health concern, and its increasing prevalence has significant health and economic importance in all nations. The condition is a multifactorial disorder with a complex aetiology. The genetic…

Machine Learning · Computer Science 2018-08-30 Basma Abdulaimma , Paul Fergus , Carl Chalmers

Statistical methods for testing aggregate rare-variant genetic associations are typically based on either burden or dispersion tests (or a combination of the two). These methods lack statistical power in the presence of diverse genetic…

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