{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:24:01Z","timestamp":1760145841746,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"national Portuguese","award":["POCI-01-0145-FEDER-022184","PTDC\/MED-GEN\/30895\/2017","DL 57\/2016\/CP1361\/CT0042","LA\/P\/0053\/2020","UIDB\/4255\/2020","UIDB\/04326\/2020"],"award-info":[{"award-number":["POCI-01-0145-FEDER-022184","PTDC\/MED-GEN\/30895\/2017","DL 57\/2016\/CP1361\/CT0042","LA\/P\/0053\/2020","UIDB\/4255\/2020","UIDB\/04326\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Genome-wide association studies (GWASs) have revealed numerous loci associated with breast cancer risk, yet the precise causal variants, their impact on molecular mechanisms, and the affected genes often remain elusive. We hypothesised that specific variants exert their influence by affecting cis-regulatory alternative splice elements. An analysis of splicing quantitative trait loci (sQTL) in healthy breast tissue from female individuals identified multiple variants linked to alterations in splicing ratios. Through colocalisation analysis, we pinpointed 43 variants within twelve genes that serve as candidate causal links between sQTL and GWAS findings. In silico splice analysis highlighted a potential mechanism for three genes\u2014FDPS, SGCE, and MRPL11\u2014where variants in proximity to or on the splice site modulate usage, resulting in alternative splice transcripts. Further in vitro\/vivo studies are imperative to fully understand how these identified changes contribute to breast oncogenesis. Moreover, investigating their potential as biomarkers for breast cancer risk could enhance screening strategies and early detection methods for breast cancer.<\/jats:p>","DOI":"10.3390\/cancers16173020","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T07:45:47Z","timestamp":1725003947000},"page":"3020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Colocalised Genetic Associations Reveal Alternative Splicing Variants as Candidate Causal Links for Breast Cancer Risk in 10 Loci"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4773-4621","authenticated-orcid":false,"given":"Andr\u00e9","family":"Besouro-Duarte","sequence":"first","affiliation":[{"name":"CINTESIS@RISE, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences, Gambelas Campus, Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3789-6648","authenticated-orcid":false,"given":"Beatriz","family":"Carrasqueiro","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biomedical Sciences, Gambelas Campus, Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"given":"Sofia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biomedical Sciences, Gambelas Campus, Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"given":"Joana M.","family":"Xavier","sequence":"additional","affiliation":[{"name":"CINTESIS@RISE, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Centro de Ci\u00eancias do Mar (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0454-9207","authenticated-orcid":false,"given":"Ana-Teresa","family":"Maia","sequence":"additional","affiliation":[{"name":"CINTESIS@RISE, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences, Gambelas Campus, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Centro de Ci\u00eancias do Mar (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature24284","article-title":"Association Analysis Identifies 65 New Breast Cancer Risk Loci","volume":"551","author":"Michailidou","year":"2017","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"D1001","DOI":"10.1093\/nar\/gkt1229","article-title":"The NHGRI GWAS Catalog, a Curated Resource of SNP-Trait Associations","volume":"42","author":"Welter","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Xavier, J.M., Magno, R., Russell, R., de Almeida, B.P., Jacinta-Fernandes, A., Duarte, A., Dunning, M., Samarajiwa, S., O\u2019Reilly, M., and Rocha, C.L. 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