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We proposed an alternative approach by investigating the shared genetic risk factors between BC and several thyroid traits. We report a positive genetic correlation between BC and thyroxine (FT4) levels (corr\u2009=\u20090.13, p-value\u2009=\u20092.0\u2009\u00d7\u200910\u22124) and a negative genetic correlation between BC and thyroid-stimulating hormone (TSH) levels (corr\u2009=\u2009\u22120.09, p-value\u2009=\u20090.03). These associations are more striking when restricting the analysis to estrogen receptor-positive BC. Moreover, the polygenic risk scores (PRS) for FT4 and hyperthyroidism are positively associated to BC risk (OR\u2009=\u20091.07, 95%CI: 1.00\u20131.13, p-value\u2009=\u20092.8\u2009\u00d7\u200910\u22122 and OR\u2009=\u20091.04, 95%CI: 1.00\u20131.08, p-value\u2009=\u20093.8\u2009\u00d7\u200910\u22122, respectively), while the PRS for TSH is inversely associated to BC risk (OR\u2009=\u20090.93, 95%CI: 0.89\u20130.97, p-value\u2009=\u20092.0\u2009\u00d7\u200910\u22123). Using the PLACO method, we detected 49 loci associated to both BC and thyroid traits (p-value\u2009&amp;lt;\u20095\u2009\u00d7\u200910\u22128), in the vicinity of 130 genes. An additional colocalization and gene-set enrichment analyses showed a convincing causal role for a known pleiotropic locus at 2q35 and revealed an additional one at 8q22.1 associated to both BC and thyroid cancer. We also found two new pleiotropic loci at 14q32.33 and 17q21.31 that were associated to both TSH levels and BC risk. Enrichment analyses and evidence of regulatory signals also highlighted brain tissues and immune system as candidates for obtaining associations between BC and TSH levels. Overall, our study sheds light on the complex interplay between BC and thyroid traits and provides evidence of shared genetic risk between those conditions.<\/jats:p>","DOI":"10.1093\/hmg\/ddad159","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T04:14:45Z","timestamp":1695442485000},"page":"38-47","source":"Crossref","is-referenced-by-count":7,"title":["Investigation of common genetic risk factors between thyroid traits and breast cancer"],"prefix":"10.1093","volume":"33","author":[{"given":"Elise A","family":"Lucotte","sequence":"first","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazdan","family":"Asgari","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Emmanuel","family":"Sugier","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"},{"name":"Universit\u00e9 de Pau et des Pays de l\u2019Adour, UMR CNRS 5142, E2S-UPPA Laboratoire de Math\u00e9matiques et de leurs Applications de Pau, , 64013 Pau , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojgan","family":"Karimi","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clo\u00e9","family":"Domenighetti","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Lesueur","sequence":"additional","affiliation":[{"name":"PSL University, Mines ParisTech Inserm, U900, Institut Curie, , 75006 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Boland-Aug\u00e9","sequence":"additional","affiliation":[{"name":"Fran\u00e7ois Jacob Institute of Biology, Commissariat \u00e0 l\u2019Energie Atomique, Paris-Saclay University National Centre of Human Genomics Research, , 91000 Evry , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia","family":"Ostroumova","sequence":"additional","affiliation":[{"name":"International Agency for Research on Cancer, WHO , 69007 Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"de Vathaire","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team of Epidemiology of radiations , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Zidane","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team of Epidemiology of radiations , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Gu\u00e9nel","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Deleuze","sequence":"additional","affiliation":[{"name":"Fran\u00e7ois Jacob Institute of Biology, Commissariat \u00e0 l\u2019Energie Atomique, Paris-Saclay University National Centre of Human Genomics Research, , 91000 Evry , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Boutron-Ruault","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Severi","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"},{"name":"University of Florence Department of Statistics, Computer Science, Applications \u201cG. Parenti\u201d, , 50121 Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Liquet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Pau et des Pays de l\u2019Adour, UMR CNRS 5142, E2S-UPPA Laboratoire de Math\u00e9matiques et de leurs Applications de Pau, , 64013 Pau , France"},{"name":"Macquarie University School of Mathematical and Physical Sciences, , 2109 Sydney , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e9r\u00e8se","family":"Truong","sequence":"additional","affiliation":[{"name":"Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team \u201cExposome and Heredity\u201d , 94807 Villejuif , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"2023121917042762800_ref1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"2023121917042762800_ref2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.07.002","article-title":"Breast cancer epidemiology, prevention, and screening. 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