{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:10:00Z","timestamp":1788977400371,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,7]]},"group-title":"Genetic and Genomic Medicine","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01 HG011405"],"award-info":[{"award-number":["R01 HG011405"]}],"id":[{"id":"https:\/\/ror.org\/00baak391","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 HG008341"],"award-info":[{"award-number":["T32 HG008341"]}],"id":[{"id":"https:\/\/ror.org\/00baak391","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Sex differences exist in complex diseases, but the genetic architecture of sex differences in quantitative clinical traits is understudied. Here, we performed sex-stratified genome-wide association studies of 508 clinical traits from electronic health records (EHRs) in 64,956 European-ancestry individuals in the Vanderbilt biobank, BioVU, with replication in the UK Biobank and Colorado Center for Personalized Medicine biobank. Most trait distributions differed significantly by sex. We identified a female-specific locus for erythrocyte distribution width at\n                  <jats:italic>PIEZO1<\/jats:italic>\n                  and sex-differentiated effect magnitudes at\n                  <jats:italic>APOE<\/jats:italic>\n                  (LDL cholesterol) and\n                  <jats:italic>SLC2AS<\/jats:italic>\n                  (uric acid) that replicated across biobanks, varied with age, and partially mediated associations with heart disease and gout. Opposite-direction sex effects were less replicable. Ascertainment bias could be addressed using inverse-probability weighting. Sex-stratified colocalization with e\u01eaTLs nominated additional candidate genes. Differential effect magnitude, not opposing effects, predominate in sex- specific genetic architecture, requiring large sample sizes for discovery that can be achieved using EHR data.\n                <\/jats:p>","DOI":"10.64898\/2026.09.02.26362069","type":"posted-content","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:55:12Z","timestamp":1788854112000},"source":"Crossref","is-referenced-by-count":0,"title":["Sex differences in the genetic architecture of clinical quantitative traits in the electronic health record"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-4969","authenticated-orcid":false,"given":"Freida","family":"Blostein","sequence":"first","affiliation":[{"name":"Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY"},{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0842-8768","authenticated-orcid":false,"given":"Banabithi","family":"Bose","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ky\u2019Era","family":"Actkins","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Lake","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Freilich","sequence":"additional","affiliation":[{"name":"Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Straub","sequence":"additional","affiliation":[{"name":"Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Niarchou","sequence":"additional","affiliation":[{"name":"Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY"},{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"},{"name":"Medical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara E.","family":"Stranger","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO"},{"name":"Ludeman Family Center for Women\u2019s Health Research, University of Colorado Anschutz, Aurora, CO"},{"name":"Colorado Center for Personalized Medicine, University of Colorado Anschutz, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea K.","family":"Davis","sequence":"additional","affiliation":[{"name":"Windreich Department of AI and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY"},{"name":"Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"},{"name":"Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"},{"name":"Associate Faculty, New York Genome Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026090910451032000_2026.09.02.26362069v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0083-1"},{"key":"2026090910451032000_2026.09.02.26362069v1.2","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2022.1548"},{"key":"2026090910451032000_2026.09.02.26362069v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.07.082"},{"key":"2026090910451032000_2026.09.02.26362069v1.4","doi-asserted-by":"crossref","unstructured":"Dennis, J. 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