Cell-type heterogeneity in adipose tissue is associated with complex traits and reveals disease-relevant cell-specific eQTLs

Adipose tissue is comprised of a heterogeneous collection of cell-types which can differentially impact disease phenotypes. We investigated cell-type heterogeneity in two population-level subcutaneous adipose tissue RNAseq datasets (TwinsUK, N =766 and GTEx, N=326). We find that adipose cell-type composition is heritable and confirm the positive association between macrophage proportion and obesity (BMI), but find a stronger BMI-independent association with DXA-derived body-fat distribution traits. Cellular heterogeneity can confound ‘omic analyses, but is rarely taken into account in analysis of solid-tissue transcriptomes. We benchmark the impact of adipose tissue cell-composition on a range of standard analyses, including phenotypegene expression association, co-expression networks and cis -eQTL discovery. We applied G x Cell Type Proportion interaction models to identify 26 cell-type specific eQTLs in 20 genes, including 4 autoimmune disease GWAS loci , demonstrating the potential of in silico deconvolution of bulk tissue to identify cell-type restricted regulatory variants.