Academic Journal
Cell-type heterogeneity in adipose tissue is associated with complex traits and reveals disease-relevant cell-specific eQTLs
| العنوان: | Cell-type heterogeneity in adipose tissue is associated with complex traits and reveals disease-relevant cell-specific eQTLs |
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| المؤلفون: | Glastonbury, C.A., Couto Alves, A., El-Sayed Moustafa, J.S., Small, K.S. |
| سنة النشر: | 2019 |
| المجموعة: | University of Southampton: e-Prints Soton |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://eprints.soton.ac.uk/494831/1/PIIS0002929719301211.pdf; Glastonbury, C.A., Couto Alves, A., El-Sayed Moustafa, J.S. and Small, K.S. (2019) Cell-type heterogeneity in adipose tissue is associated with complex traits and reveals disease-relevant cell-specific eQTLs. American Journal of Human Genetics, 103 - 1024. (doi:10.1016/j.ajhg.2019.03.025 ). |
| الاتاحة: | https://eprints.soton.ac.uk/494831/ https://eprints.soton.ac.uk/494831/1/PIIS0002929719301211.pdf |
| Rights: | cc_by_4 |
| رقم الانضمام: | edsbas.80E51097 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |