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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>It is well known that genetic variants contribute to cellular sensitivity to chemotherapeutic agents and ionizing radiation (IR). The aim of this study was to identify single nucleotide polymorphisms (SNPs) and genes associated with the spectrum of normal cellular sensitivity of lymphoblastoid cell lines (LCLs) towards ionizing radiation and mitomycin C (MMC). In the first step, we determined the viability of LCLs established from male participants of the Berlin Aging Study II (BASE-II) aged \u226562 years following treatments with increasing doses of IR (n = 137 cell lines) or MMC (n = 140 cell lines) using the alamarBlue assay. Results from intra-experimental triplicates and three independent experiments for each cell line and treatment were used to calculate the area under the curves (AUCs) representing the specific sensitivity to IR and MMC of each LCL. The data from these experiments were subsequently used as outcomes in genome-wide association studies (GWASs). In addition, we calculated polygenic risk scores (PGS) from UK Biobank GWAS results for four cancer-related phenotypes and assessed the extent to which the variance in the IR and MMC sensitivity is explained by these PGS. The GWAS analyses revealed one variant, rs74728080, located in CDH13 on chromosome 16, to show genome-wide significant (p &lt; 5 \u00d7 10\u22128, \u00df = 2.81) association with cellular viability after treatment with IR. In the GWAS on MMC sensitivity the most interesting signal was elicited by SNP rs113978558 in an intron of the PLD5 gene on chromosome 1 (p = 9.232 \u00d7 10\u22128; \u00df = 1.44). Several other SNPs with statistically suggestive (i.e., p &lt; 1 \u00d7 10\u22125) evidence of association with IR or MMC sensitivity were identified. PGS calculations from GWAS of four cancer-related traits in UKB explained ~5% and ~3% of phenotypic variance in IR- and MMC-induced cell viability, respectively. The genome-wide significant association of rs74728080 with IR sensitivity and the location of this variant in CDH13 is interesting and functionally highly plausible given its known involvement in oxidative stress response and function as a tumor suppressor. Taken together, our novel data suggest that CDH13 may be genuinely involved in regulating cellular IR sensitivity.<\/jats:p>","DOI":"10.3390\/ijms27156826","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:09:42Z","timestamp":1785398982000},"page":"6826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CDH13 Is Associated with Cellular Viability After Exposure to Ionizing Radiation Using Genome-Wide Screening"],"prefix":"10.3390","volume":"27","author":[{"given":"Hannah-Lena","family":"Schmidt","sequence":"first","affiliation":[{"name":"Biology of Aging Working Group, Department of Endocrinology and Metabolism, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olena","family":"Ohlei","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics, University of L\u00fcbeck, 23562 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Herwest","sequence":"additional","affiliation":[{"name":"Biology of Aging Working Group, Department of Endocrinology and Metabolism, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Salewsky","sequence":"additional","affiliation":[{"name":"Biology of Aging Working Group, Department of Endocrinology and Metabolism, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0108-124X","authenticated-orcid":false,"given":"Lars","family":"Bertram","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics, University of L\u00fcbeck, 23562 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-2523","authenticated-orcid":false,"given":"Ilja","family":"Demuth","sequence":"additional","affiliation":[{"name":"Biology of Aging Working Group, Department of Endocrinology and Metabolism, Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"BCRT\u2014Berlin Institute of Health Center for Regenerative Therapies, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.radonc.2014.03.024","article-title":"Estimating the demand for radiotherapy from the evidence: A review of changes from 2003 to 2012","volume":"112","author":"Barton","year":"2014","journal-title":"Radiother. 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