Dataset Information

Expression quantitative trait loci mapping with multivariate sparse partial least squares regression.

ABSTRACT: Expression quantitative trait loci (eQTL) mapping concerns finding genomic variation to elucidate variation of expression traits. This problem poses significant challenges due to high dimensionality of both the gene expression and the genomic marker data. We propose a multivariate response regression approach with simultaneous variable selection and dimension reduction for the eQTL mapping problem. Transcripts with similar expression are clustered into groups, and their expression profiles are viewed as a multivariate response. Then, we employ our recently developed sparse partial least-squares regression methodology to select markers associated with each cluster of genes. We demonstrate with extensive simulations that our eQTL mapping with multivariate response sparse partial least-squares regression (M-SPLS eQTL) method overcomes the issue of multiple transcript- or marker-specific analyses, thereby avoiding potential elevation of type I error. Additionally, joint analysis of multiple transcripts by multivariate response regression increases power for detecting weak linkages. We illustrate that M-SPLS eQTL compares competitively with other approaches and has a number of significant advantages, including the ability to handle highly correlated genotype data and computational efficiency. We provide an application of this methodology to a mouse data set concerning obesity and diabetes.

SUBMITTER: Chun H

PROVIDER: S-EPMC2674843 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression quantitative trait loci mapping with multivariate sparse partial least squares regression.

Chun Hyonho H Keles Sündüz S

Genetics 20090306 1

Expression quantitative trait loci (eQTL) mapping concerns finding genomic variation to elucidate variation of expression traits. This problem poses significant challenges due to high dimensionality of both the gene expression and the genomic marker data. We propose a multivariate response regression approach with simultaneous variable selection and dimension reduction for the eQTL mapping problem. Transcripts with similar expression are clustered into groups, and their expression profiles are v ...[more]

PMID: 19270271

Similar Datasets

Project description:BackgroundExpression quantitative trait loci (eQTL) have been identified using tissue or cell samples from diverse human populations, thus enhancing our understanding of regulation of gene expression. However, few studies have attempted to identify eQTL in racially admixed populations such as Hispanics.MethodsWe performed a systematic eQTL study to identify regulatory variants of gene expression in whole blood from 121 Puerto Rican children with (n = 63) and without (n = 58) asthma. Genome-wide genotyping was conducted using the Illumina Omni2.5M Bead Chip, and gene expression was assessed using the Illumina HT-12 microarray. After completing quality control, we performed a pair-wise genome analysis of ~15 K transcripts and ~1.3 M SNPs for both local and distal effects. This analysis was conducted under a regression framework adjusting for age, gender and principal components derived from both genotypic and mRNA data. We used a false discovery rate (FDR) approach to identify significant eQTL signals, which were next compared to top eQTL signals from existing eQTL databases. We then performed a pathway analysis for our top genes.ResultsWe identified 36,720 local pairs in 3,391 unique genes and 1,851 distal pairs in 446 unique genes at FDR <0.05, corresponding to unadjusted P values lower than 1.5x10-4 and 4.5x10-9, respectively. A significant proportion of genes identified in our study overlapped with those identified in previous studies. We also found an enrichment of disease-related genes in our eQTL list.ConclusionsWe present results from the first eQTL study in Puerto Rican children, who are members of a unique Hispanic cohort disproportionately affected with asthma, prematurity, obesity and other common diseases. Our study confirmed eQTL signals identified in other ethnic groups, while also detecting additional eQTLs unique to our study population. The identified eQTLs will help prioritize findings from future genome-wide association studies in Puerto Ricans.

Dataset Information

Expression quantitative trait loci mapping with multivariate sparse partial least squares regression.

Publications

Expression quantitative trait loci mapping with multivariate sparse partial least squares regression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure