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There is epidemiologic evidence showing that women with celiac disease have reduced risk of later developing breast cancer, however, the etiology of this association is unclear. Here, we assess the extent of genetic overlap between the two diseases. Through analyses of summary statistics on densely genotyped immunogenic regions, we show a significant genetic correlation ( r  = −0.17, s.e. 0.05,  P  < 0.001) and overlap ( P   permuted  < 0.001) between celiac disease and breast cancer. Using individual-level genotype data from a Swedish cohort, we find higher genetic susceptibility to celiac disease summarized by polygenic risk scores to be associated with lower breast cancer risk (OR per-SD , 0.94, 95% CI 0.91 to 0.98). Common single nucleotide polymorphisms between the two diseases, with low  P -values ( P   CD  < 1.00E-05,  P   BC  ≤ 0.05), mapped onto genes enriched for immunoregulatory and apoptotic processes. Our results suggest that the link between breast cancer and celiac disease is due to a shared polygenic variation of immune related regions, uncovering pathways which might be important for their development.

Common shared genetic variation behind decreased risk of breast cancer in celiac disease