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Motivated by empirical arguments that are well-known from the genome-wide association studies (GWAS) literature, we study the statistical properties of linear mixed models (LMMs) applied to GWAS. First, we study the sensitivity of LMMs to…

Quantitative Methods · Quantitative Biology 2021-11-09 Haohan Wang , Bryon Aragam , Eric Xing

Mendelian randomization (MR) is an epidemiological method that can be used to strengthen causal inference regarding the relationship between a modifiable environmental exposure and a medically relevant trait and to estimate the magnitude of…

Quantitative Methods · Quantitative Biology 2023-08-30 David M Evans , George Davey Smith , Gunn-Helen Moen

We propose a random-effects approach to missing values for generalized linear mixed model (GLMM) analysis. The method converts a GLMM with missing covariates to another GLMM without missing covariates. The standard GLMM analysis tools for…

Methodology · Statistics 2026-01-01 Thuan Nguyen , Jiangshan Zhang , Jiming Jiang

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

Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can…

Genomics · Quantitative Biology 2013-05-28 Jennifer Listgarten , Christoph Lippert , Eun Yong Kang , Jing Xiang , Carl M. Kadie , David Heckerman

Associating genetic markers with a multidimensional phenotype is an important yet challenging problem. In this work, we establish the equivalence between two popular methods: kernel-machine regression (KMR), and kernel distance covariance…

Machine Learning · Statistics 2014-04-03 Wen-Yu Hua , Debashis Ghosh

Adaptation in response to selection on polygenic phenotypes may occur via subtle allele frequencies shifts at many loci. Current population genomic techniques are not well posed to identify such signals. In the past decade, detailed…

Populations and Evolution · Quantitative Biology 2014-08-19 Jeremy J. Berg , Graham Coop

Through genome-wide association studies (GWAS), disease susceptible genetic variables can be identified by comparing the genetic data of individuals with and without a specific disease. However, the discovery of these associations poses a…

Machine Learning · Computer Science 2023-08-15 Zhendong Sha , Yuanzhu Chen , Ting Hu

Unmeasured or latent variables are often the cause of correlations between multivariate measurements, which are studied in a variety of fields such as psychology, ecology, and medicine. For Gaussian measurements, there are classical tools…

Machine Learning · Computer Science 2022-01-28 Łukasz Kidziński , Francis K. C. Hui , David I. Warton , Trevor Hastie

A new nonparametric graphical test of significance of a covariate in functional GLM is proposed. Our approach is especially interesting due to its functional graphical interpretation of the results. As such it is able to find not only if…

Methodology · Statistics 2019-02-14 Tomas Mrkvicka , Tomas Roskovec , Michael Rost

The widely used genetic pleiotropic analysis of multiple phenotypes are often designed for examining the relationship between common variants and a few phenotypes. They are not suited for both high dimensional phenotypes and high…

Machine Learning · Statistics 2015-12-04 Panpan Wang , Mohammad Rahman , Li Jin , Momiao Xiong

It is now well documented that genetic covariance between functionally related traits leads to an uneven distribution of genetic variation across multivariate trait combinations, and possibly a large part of phenotype-space that is…

Applications · Statistics 2022-10-24 Damian Pavlyshyn , Iain M. Johnstone , Jacqueline L. Sztepanacz

Genome-wide association study (GWAS) tests single nucleotide polymorphism (SNP) markers across the genome to localize the underlying causal variant of a trait. Because causal variants are seldom observed directly, a surrogate model based on…

Populations and Evolution · Quantitative Biology 2023-03-03 Hanbin Lee , Moo Hyuk Lee

Substantial progress has been made in identifying single genetic variants predisposing to common complex diseases. Nonetheless, the genetic etiology of human diseases remains largely unknown. Human complex diseases are likely influenced by…

Methodology · Statistics 2014-05-27 Zihuai He , Min Zhang , Xiaowei Zhan , Qing Lu

One of the major developments in recent years in the search for missing heritability of human phenotypes is the adoption of linear mixed-effects models (LMMs) to estimate heritability due to genetic variants which are not significantly…

Populations and Evolution · Quantitative Biology 2013-05-28 David Golan , Saharon Rosset

A large number of recent genome-wide association studies (GWASs) for complex phenotypes confirm the early conjecture for polygenicity, suggesting the presence of large number of variants with only tiny or moderate effects. However, due to…

Genomics · Quantitative Biology 2018-05-01 Mingwei Dai , Xiang Wan , Hao Peng , Yao Wang , Yue Liu , Jin Liu , Zongben Xu , Can Yang

Complex, non-additive genetic interactions are common and can be critical in determining phenotypes. Genome-wide association studies (GWAS) and similar statistical studies of linkage data, however, assume additive models of gene…

Genomics · Quantitative Biology 2010-03-05 Nikita A. Sakhanenko , David J. Galas

In genetic association studies, rare variants with extremely small allele frequency play a crucial role in complex traits, and the set-based testing methods that jointly assess the effects of groups of single nucleotide polymorphisms (SNPs)…

Methodology · Statistics 2020-03-13 Shonosuke Sugasawa , Hisashi Noma

We provide a view on high-dimensional statistical inference for genome-wide association studies (GWAS). It is in part a review but covers also new developments for meta analysis with multiple studies and novel software in terms of an…

Applications · Statistics 2020-02-17 Claude Renaux , Laura Buzdugan , Markus Kalisch , Peter Bühlmann

Familywise error rate (FWER) has been a cornerstone in simultaneous inference for decades, and the classical Bonferroni method has been one of the most prominent frequentist approaches for controlling FWER. The present article studies the…

Statistics Theory · Mathematics 2021-12-07 Monitirtha Dey , Subir Kumar Bhandari