MiXcan: a framework for cell-type-aware transcriptome-wide association studies with an application to breast cancer.

Because adipocytes are the predominant stromal cell type in mammary tissue, we also performed follow-up analyses using the S-PrediXcan subcutaneous fat model and discovered a highly significant ( p value=2.1 × 10 −20 ) association of ZNF703 with increased breast cancer risk in the four-fold larger BCAC/DRIVE dataset, consistent with the MiXcan stromal cell results in the DRIVE data only.

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MiXcan estimated cell-type-specific GReX prediction models for these four genes (Supplementary Data 2) , and different associations with breast cancer risk in epithelial and stromal cells that did not reach statistical significance in part because of the larger number of model parameters compared with PrediXcan.

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