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Both evolutionary life-history theory and evidence from studies of individual ER + BC risk variants suggest that increased genetic ER + BC risk is associated with faster maturation, earlier reproduction, and\/or increased reproductive success (i.e. there is a trade-off), but it is unclear how well this pattern is replicated when considering the polygenic architecture of these traits after controlling for potential biases. Here, we estimate genome-wide genetic correlations between ER + BC risk and three reproductive traits (age at menarche, age at first birth, and the number of children) using genomic restricted maximum-likelihood analyses on Lifelines biobank data and linkage disequilibrium score regressions on population and family-based genome-wide association study data. Regardless of the data or method used, genetic correlations were low and not statistically significant. Further analyses decomposing genome-wide genetic variance into local regions detected only three loci exhibiting significant pleiotropy between ER + BC risk and age at menarche, suggesting little shared genetic architecture between ER + BC risk and reproductive traits. Thus, the role of life-history trade-offs in shaping ER + BC risk in European populations appears, at most, small, and the evolutionary processes giving rise to this life-threatening disease remain unclear. Future studies could examine the impact of evolutionary mismatches in shaping ER + BC risk, where conducting longitudinal studies on populations transitioning to reproductive patterns observed in contemporary European populations would be most useful.<\/jats:p>","DOI":"10.1093\/molbev\/msag222","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T12:08:38Z","timestamp":1788178118000},"source":"Crossref","is-referenced-by-count":0,"title":["No genome-wide correlations and little shared genetic architecture between reproductive life-history traits and estrogen receptor-positive breast cancer risk"],"prefix":"10.1093","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9370-9681","authenticated-orcid":false,"given":"Euan A","family":"Young","sequence":"first","affiliation":[{"name":"Groningen Institute for Evolutionary Life Sciences, University of Groningen , Groningen 9747 AG ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9736-0405","authenticated-orcid":false,"given":"E Yagmur","family":"Erten","sequence":"additional","affiliation":[{"name":"Groningen Institute for Evolutionary Life Sciences, University of Groningen , Groningen 9747 AG ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0856-1294","authenticated-orcid":false,"given":"Erik","family":"Postma","sequence":"additional","affiliation":[{"name":"Centre for Ecology and Conservation, University of Exeter , Penryn TR10 9FE ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2128-7587","authenticated-orcid":false,"given":"Virpi","family":"Lummaa","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Turku , Turku 20014 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2613-1506","authenticated-orcid":false,"given":"Bert","family":"van der Vegt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen , Groningen 9713 GZ ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-4471","authenticated-orcid":false,"given":"Geertruida H","family":"de Bock","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University Medical Center Groningen, University of Groningen , Groningen 9713 GZ ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8769-0099","authenticated-orcid":false,"given":"Hannah L","family":"Dugdale","sequence":"additional","affiliation":[{"name":"Groningen 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