{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:56:01Z","timestamp":1791035761492,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Second\u2010generation antipsychotics (SGA) are widely used for treating psychiatric disorders; however, their use is associated with an increased risk of metabolic syndrome (MetS). To identify common genetic associations of SGA\u2010induced metabolic syndrome (SGA\u2010MetS), we conducted a genome\u2010wide association study (GWAS) in a diverse patient population within the BioVU and Bio\n                    <jats:italic>M<\/jats:italic>\n                    e electronic health records (EHRs)\u2010linked biobanks. Additionally, we performed Mendelian Randomization (MR) analysis to investigate the association between the individual metabolic parameters comprising MetS (body mass index [BMI], fasting glucose, blood pressure, HDL, and triglycerides) and SGA\u2010MetS. The meta\u2010analysis of European ancestry GWAS from BioVU and Bio\n                    <jats:italic>M<\/jats:italic>\n                    e (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20099248) identified a genome\u2010wide signal (rs61900075,\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u2009\u22120.27, SE\u2009=\u20090.05,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20091.6\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) on chromosome 11. Multiple associated variants met the suggestive level of association (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    ) in the\n                    <jats:italic>PELO\u2010ITGA1<\/jats:italic>\n                    locus on chromosome 5 and were associated among the Hispanic Ancestry within Bio\n                    <jats:italic>M<\/jats:italic>\n                    e. The meta\u2010analysis of the African Ancestry patients of BioVU and Bio\n                    <jats:italic>M<\/jats:italic>\n                    e (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20092018) identified multiple genome\u2010wide signals that were functionally mapped to\n                    <jats:italic>NPPC\u2010DIS3L2<\/jats:italic>\n                    in chromosome 2. Finally, the inverse\u2010variance weighted average MR (BMI: OR\u2009=\u20091.2, 95% CI: 1.1\u20131.4,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002) showed that genetically predicted, higher BMI was associated with an increased risk of SGA\u2010MetS. Similar results were seen in the sensitivity analyses using the weighted median and Egger MR. This study identified novel variants for SGA\u2010MetS and suggested a role of BMI in increasing the risk of SGA\u2010MetS. The findings highlight the value of EHR biobanks for identifying the genetics underlying SGA\u2010MetS. The associations in chromosome 2 and 5 will need further replication.\n                  <\/jats:p>","DOI":"10.1111\/cts.70216","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:41:43Z","timestamp":1745282503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genome Wide Association Study (\n                    <scp>GWAS<\/scp>\n                    ) Identifies Novel Genetic Loci for Second\u2010Generation Antipsychotics (\n                    <scp>SGA<\/scp>\n                    )\u2010Induced Metabolic Syndrome (\n                    <scp>MetS<\/scp>\n                    )"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1652-3773","authenticated-orcid":false,"given":"Nihal","family":"El Rouby","sequence":"first","affiliation":[{"name":"James L Winkle College of Pharmacy University of Cincinnati  Cincinnati OH USA"},{"name":"Department of Psychiatry &amp; Behavioral Neuroscience College of Medicine, University of Cincinnati  Cincinnati Ohio USA"},{"name":"St. Elizabeth Healthcare  Edgewood Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniwaa","family":"Owusu\u2010Obeng","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Preuss","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lee","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics VUMC  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Nadukuru","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2580-1405","authenticated-orcid":false,"given":"Sara L.","family":"Van Driest","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Vanderbilt University Medical Center (VUMC)  Nashville Tennessee USA"},{"name":"All of Us Research Program National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Mosley","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics VUMC  Nashville Tennessee USA"},{"name":"Department of Medicine VUMC  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"DelBello","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Behavioral Neuroscience College of Medicine, University of Cincinnati  Cincinnati Ohio USA"},{"name":"College of Medicine University of Cincinnati  Cincinnati OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612821666150619092903"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.156"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14030238"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806043382302"},{"issue":"2","key":"e_1_2_8_6_1","article-title":"Exposure to Second\u2010Generation Antipsychotics and Risk of Type 2 Diabetes Mellitus in Adolescents and Young Adults: A Nationwide Study in Taiwan","volume":"80","author":"Tu T. 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