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• W2945986103 abstract "Abstract Expression QTL (eQTL) detection has emerged as an important tool for unraveling the relationship between genetic risk factors and disease or clinical phenotypes. Most studies are predicated on the assumption that only a single causal variant explains the association signal in each interval. This greatly simplifies the statistical modeling, but is liable to biases in scenarios where multiple local causal-variants are responsible. Here, our primary goal was to address the prevalence of secondary cis-eQTL signals regulating peripheral blood gene expression locally, utilizing two large human cohort studies, each &gt;2500 samples with accompanying whole genome genotypes. The CAGE (Consortium for the Architecture of Gene Expression) dataset is a compendium of Illumina microarray studies, and the Framingham Heart Study is a two-generation Affymetrix dataset. We also describe Bayesian colocalization analysis of the extent of sharing of cis-eQTL detected in both studies as well as with the BIOS RNAseq dataset. Stepwise conditional modeling demonstrates that multiple eQTL signals are present for ∼40% of over 3500 eGenes in both microarray datasets, and that the number of loci with additional signals reduces by approximately two-thirds with each conditioning step. Although &lt;20% of the peak signals across platforms fine map to the same credible interval, the colocalization analysis finds that as many as 50–60% of the primary eQTL are actually shared. Subsequently, colocalization of eQTL signals with GWAS hits detected 1349 genes whose expression in peripheral blood is associated with 591 human phenotype traits or diseases, including enrichment for genes with regulatory functions. At least 10%, and possibly as many as 40%, of eQTL-trait colocalized signals are due to nonprimary cis-eQTL peaks, but just one-quarter of these colocalization signals replicated across the gene expression datasets. Our results are provided as a web-based resource for visualization of multi-site regulation of gene expression and its association with human complex traits and disease states." @default.
• W2945986103 created "2019-05-29" @default.
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• W2945986103 date "2019-05-22" @default.
• W2945986103 modified "2023-10-09" @default.
• W2945986103 title "Comprehensive Multiple eQTL Detection and Its Application to GWAS Interpretation" @default.
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• W2945986103 doi "https://doi.org/10.1534/genetics.119.302091" @default.
• W2945986103 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6614888" @default.
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• W2945986103 hasPublicationYear "2019" @default.
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