title: Exploiting Linkage Disequilibrium for Ultrahigh-Dimensional Genome-Wide Data with an Integrated Statistical Approach.
abstract: Genome-wide data with millions of single-nucleotide polymorphisms (SNPs) can be highly correlated due to linkage disequilibrium (LD). The ultrahigh dimensionality of big data brings unprecedented challenges to statistical modeling such as noise accumulation, the curse of dimensionality, computational burden, spurious correlations, and a processing and storing bottleneck. The traditional statistical approaches lose their power due to [Formula: see text] (n is the number of observations and p is the number of SNPs) and the complex correlation structure among SNPs. In this article, we propose an integrated distance correlation ridge regression (DCRR) approach to accommodate the ultrahigh dimensionality, joint polygenic effects of multiple loci, and the complex LD structures. Initially, a distance correlation (DC) screening approach is used to extensively remove noise, after which LD structure is addressed using a ridge penalized multiple logistic regression (LRR) model. The false discovery rate, true positive discovery rate, and computational cost were simultaneously assessed through a large number of simulations. A binary trait of Arabidopsis thaliana, the hypersensitive response to the bacterial elicitor AvrRpm1, was analyzed in 84 inbred lines (28 susceptibilities and 56 resistances) with 216,130 SNPs. Compared to previous SNP discovery methods implemented on the same data set, the DCRR approach successfully detected the causative SNP while dramatically reducing spurious associations and computational time.
authors.affiliation: Department of Mathematics and Statistics, Utah State University, Logan, Utah 84322.
authors.forename: Michelle
authors.initials: M
authors.lastname: Carlsen
authors.affiliation: Department of Mathematics and Statistics, Utah State University, Logan, Utah 84322 Guifang.fu@usu.edu.
authors.forename: Guifang
authors.initials: G
authors.lastname: Fu
authors.affiliation: Forage and Range Research Laboratory, U.S. Department of Agriculture-Agricultural Research Service, Logan, Utah 84322.
authors.forename: Shaun
authors.initials: S
authors.lastname: Bushman
authors.affiliation: Department of Mathematics and Statistics, Utah State University, Logan, Utah 84322.
authors.forename: Christopher
authors.initials: C
authors.lastname: Corcoran
mesh_terms: D000465:Algorithms; D000483:Alleles; D003198:Computer Simulation; D056426:Genetic Loci; D016678:Genome; D055106:Genome-Wide Association Study / Q000379:methods*; D023281:Genomics / Q000379:methods*; D005838:Genotype; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
keywords: GWAS; GenPred; case–control; feature screening; genomic selection; large-scale modeling; linkage disequilibrium; shared data resource