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

Abstract 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...

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Autores principales:	Emilio Ugalde-Morales, Jingmei Li, Keith Humphreys, Jonas F. Ludvigsson, Haomin Yang, Per Hall, Kamila Czene
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e4a80008cb645d587704214157f7eee
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spelling	oai:doaj.org-article:7e4a80008cb645d587704214157f7eee2021-12-02T16:06:38ZCommon shared genetic variation behind decreased risk of breast cancer in celiac disease10.1038/s41598-017-06287-92045-2322https://doaj.org/article/7e4a80008cb645d587704214157f7eee2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06287-9https://doaj.org/toc/2045-2322Abstract 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 (ORper-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.Emilio Ugalde-MoralesJingmei LiKeith HumphreysJonas F. LudvigssonHaomin YangPer HallKamila CzeneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emilio Ugalde-Morales Jingmei Li Keith Humphreys Jonas F. Ludvigsson Haomin Yang Per Hall Kamila Czene Common shared genetic variation behind decreased risk of breast cancer in celiac disease
description	Abstract 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 (ORper-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.
format	article
author	Emilio Ugalde-Morales Jingmei Li Keith Humphreys Jonas F. Ludvigsson Haomin Yang Per Hall Kamila Czene
author_facet	Emilio Ugalde-Morales Jingmei Li Keith Humphreys Jonas F. Ludvigsson Haomin Yang Per Hall Kamila Czene
author_sort	Emilio Ugalde-Morales
title	Common shared genetic variation behind decreased risk of breast cancer in celiac disease
title_short	Common shared genetic variation behind decreased risk of breast cancer in celiac disease
title_full	Common shared genetic variation behind decreased risk of breast cancer in celiac disease
title_fullStr	Common shared genetic variation behind decreased risk of breast cancer in celiac disease
title_full_unstemmed	Common shared genetic variation behind decreased risk of breast cancer in celiac disease
title_sort	common shared genetic variation behind decreased risk of breast cancer in celiac disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7e4a80008cb645d587704214157f7eee
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Common shared genetic variation behind decreased risk of breast cancer in celiac disease

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