Dataset Information

Rapid and robust association mapping of expression quantitative trait loci.

ABSTRACT: We applied a simple and efficient two-step method to analyze a family-based association study of gene expression quantitative trait loci (eQTL) in a mixed model framework. This two-step method produces very similar results to the full mixed model method, with our method being significantly faster than the full model. Using the Genetic Analysis Workshop 15 (GAW15) Problem 1 data, we demonstrated the value of data filtering for reducing the number of tests and controlling the number of false positives. Specifically, we showed that removing non-expressed genes by filtering on expression variability effectively reduced the number of tests by nearly 50%. Furthermore, we demonstrated that filtering on genotype counts substantially reduced spurious detection. Finally, we restricted our analysis to the markers and transcripts that were closely located. We found five times more signals in close proximity (cis-) to transcripts than in our genome-wide analysis. Our results suggest that careful pre-filtering and partitioning of data are crucial for controlling false positives and allowing detection of genuine effects in genetic analysis of gene expression.

SUBMITTER: Lam AC

PROVIDER: S-EPMC2367564 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Rapid and robust association mapping of expression quantitative trait loci.

Lam Alex C AC Schouten Michael M Aulchenko Yurii S YS Haley Chris S CS de Koning Dirk-Jan DJ

BMC proceedings 20071218

We applied a simple and efficient two-step method to analyze a family-based association study of gene expression quantitative trait loci (eQTL) in a mixed model framework. This two-step method produces very similar results to the full mixed model method, with our method being significantly faster than the full model. Using the Genetic Analysis Workshop 15 (GAW15) Problem 1 data, we demonstrated the value of data filtering for reducing the number of tests and controlling the number of false posit ...[more]

PMID: 18466488

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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.

Project description:BackgroundThe conversion of lignocellulosic biomass from agricultural waste into biofuels and chemicals is considered a promising way to provide sustainable low carbon products without compromising food security. However, the use of lignocellulosic biomass for biofuel and chemical production is limited by the cost-effectiveness of the production process due to its recalcitrance to enzymatic hydrolysis and fermentable sugar release (i.e., saccharification). Rice straw is a particularly attractive feedstock because millions of tons are currently burned in the field each year for disposal. The aim of this study was to explore the underlying natural genetic variation that impacts the recalcitrance of rice (Oryza sativa) straw to enzymatic saccharification. Ultimately, we wanted to investigate whether we could identify genetic markers that could be used in rice breeding to improve commercial cultivars for this trait. Here, we describe the development and characterization of a Vietnamese rice genome-wide association panel, high-throughput analysis of rice straw saccharification and lignin content, and the results from preliminary genome-wide association studies (GWAS) of the combined data sets. We identify both QTL and plausible candidate genes that may have an impact on the saccharification of rice straw.ResultsWe assembled a diversity panel comprising 151 rice genotypes (Indica and Japonica types) from commercial, historical elite cultivars, and traditional landraces grown in Vietnam. The diversity panel was genotyped using genotype by sequencing (GBS) methods yielding a total of 328,915 single nucleotide polymorphisms (SNPs). We collected phenotypic data from stems of these 151 genotypes for biomass saccharification and lignin content. Using GWAS on the indica genotypes over 2 years we identified ten significant QTL for saccharification (digestibility) and seven significant QTL for lignin. One QTL on chromosome 11 occurred in both GWAS for digestibility and for lignin. Seven QTL for digestibility, on CH2, CH6, CH7, CH8, and CH11, were observed in both years of the study. The QTL regions for saccharification include three potential candidate genes that have been previously reported to influence digestibility: OsAT10; OsIRX9; and OsMYB58/63-L.ConclusionsDespite the difficulties associated with multi-phasic analysis of complex traits in novel germplasm, a moderate resolution GWAS successfully identified genetic associations encompassing both known and/or novel genes involved in determining the saccharification potential and lignin content of rice straw. Plausible candidates within QTL regions, in particular those with roles in cell wall biosynthesis, were identified but will require validation to confirm their value for application in rice breeding.

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Rapid and robust association mapping of expression quantitative trait loci.

Publications

Rapid and robust association mapping of expression quantitative trait loci.

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