{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:10Z","timestamp":1792787590832,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["R56 HL134653"],"award-info":[{"award-number":["R56 HL134653"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Heart, Lung, and Blood Institute","award":["R01HL126130"],"award-info":[{"award-number":["R01HL126130"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Testosterone is a key determinant of red blood cell (RBC) biology and susceptibility to hemolysis; however, its contribution to donor-dependent variation in RBC quality and transfusion effectiveness remains unclear. Using data from 2,357 male participants in the NHLBI REDS-III RBC-Omics study, we quantified plasma total testosterone, free testosterone (bioavailable form), and androstenedione and evaluated their associations with donor characteristics, RBC hemolysis, and recipient post-transfusion hemoglobin increments, a clinical measure of RBC transfusion effectiveness. Subphysiological testosterone concentrations were common (~35%) and independently associated with increased storage and osmotic hemolysis. Frequent blood donations were independently associated with lower circulating free testosterone concentrations, even after adjustment for demographic and hematologic factors. Genome-wide association analyses identified loci associated with circulating testosterone, including regions near\n                    <jats:italic>SHBG<\/jats:italic>\n                    ,\n                    <jats:italic>TNFSF12<\/jats:italic>\n                    , and the long noncoding RNA\n                    <jats:italic>BALR6<\/jats:italic>\n                    . Several testosterone variants were associated with RBC transfusion effectiveness. Specifically, variants associated with lower testosterone (e.g.,\n                    <jats:italic>TNFSF12<\/jats:italic>\n                    ) corresponded to higher post-transfusion hemoglobin increments (+9%), whereas\n                    <jats:italic>BALR6<\/jats:italic>\n                    variants associated with higher testosterone were linked to reduced hemoglobin increments (\u201340%). In contrast, androstenedione-associated variants were not related to hemolysis or transfusion outcomes. Together, these findings demonstrate that genetic and physiologic variation in testosterone contributes to inter-individual variability in RBC quality and transfusion effectiveness.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.208861","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:00:48Z","timestamp":1791907248000},"source":"Crossref","is-referenced-by-count":0,"title":["Plasma testosterone heterogeneity reveals genetic and demographic determinants of donor health and red blood cell quality"],"prefix":"10.1172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9829-2934","authenticated-orcid":true,"given":"Fang","family":"Fang","sequence":"first","affiliation":[{"name":"Genomics and Applied Public Health Center, RTI International, Durham, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nareg","family":"Roubinian","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Northern California Division of Research, Oakland, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xutao","family":"Deng","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie","family":"Kemmler","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jost","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Touraj","family":"Shokati","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Christians","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2582-3786","authenticated-orcid":true,"given":"Grier P.","family":"Page","sequence":"additional","affiliation":[{"name":"Fellow program, RTI International, Atlanta, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6558-0913","authenticated-orcid":true,"given":"Tamir","family":"Kanias","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,13]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/208861\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:00:48Z","timestamp":1791907248000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/208861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,13]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.208861"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.208861","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,13]]}}}