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• W2951804967 abstract "Adipose tissue is an important endocrine organ with a role in many cardiometabolic diseases. It is comprised of a heterogeneous collection of cell types that can differentially impact disease phenotypes. Cellular heterogeneity can also confound -omic analyses but is rarely taken into account in analysis of solid-tissue transcriptomes. Here, we investigate cell-type heterogeneity in two population-level subcutaneous adipose-tissue RNA-seq datasets (TwinsUK, n = 766 and the Genotype-Tissue Expression project [GTEx], n = 326) by estimating the relative proportions of four distinct cell types (adipocytes, macrophages, CD4+ T cells, and micro-vascular endothelial cells). We find significant cellular heterogeneity within and between the TwinsUK and GTEx adipose datasets. We find that adipose cell-type composition is heritable and confirm the positive association between adipose-resident macrophage proportion and obesity (high BMI), but we find a stronger BMI-independent association with dual-energy X-ray absorptiometry (DXA) derived body-fat distribution traits. We benchmark the impact of adipose-tissue cell composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks, and cis-eQTL discovery. Our results indicate that it is critical to account for cell-type composition when combining adipose transcriptome datasets in co-expression analysis and in differential expression analysis with obesity-related traits. We applied gene expression by cell-type proportion interaction models (G × Cell) to identify 26 cell-type-specific expression quantitative trait loci (eQTLs) in 20 genes, including four autoimmune disease genome-wide association study (GWAS) loci. These results identify cell-specific eQTLs and demonstrate the potential of in silico deconvolution of bulk tissue to identify cell-type-restricted regulatory variants." @default.
• W2951804967 created "2019-06-27" @default.
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• W2951804967 date "2019-06-01" @default.
• W2951804967 modified "2023-10-15" @default.
• W2951804967 title "Cell-Type Heterogeneity in Adipose Tissue Is Associated with Complex Traits and Reveals Disease-Relevant Cell-Specific eQTLs" @default.
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• W2951804967 doi "https://doi.org/10.1016/j.ajhg.2019.03.025" @default.
• W2951804967 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6556877" @default.
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