Mitochondrial-nuclear epistasis underlying phenotypic variation in breast cancer pathology

Abstract The interplay between genes harboring single nucleotide polymorphisms (SNPs) is vital to better understand underlying contributions to the etiology of breast cancer. Much attention has been paid to epistasis between nuclear genes or mutations in the mitochondrial genome. However, there is limited understanding about the epistatic effects of genetic variants in the nuclear and mitochondrial genomes jointly on breast cancer. We tested the interaction of germline SNPs in the mitochondrial (mtSNPs) and nuclear (nuSNPs) genomes of female breast cancer patients in The Cancer Genome Atlas (TCGA) for association with morphological features extracted from hematoxylin and eosin (H&E)-stained pathology images. We identified 115 significant (q-value