{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:52:23Z","timestamp":1791557543652,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K01\u2010DK\u2010137031"],"award-info":[{"award-number":["K01\u2010DK\u2010137031"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K23\u2010AR\u2010084061"],"award-info":[{"award-number":["K23\u2010AR\u2010084061"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Anti\u2013\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010glycoprotein I (anti\u2010\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI) antibodies are central to antiphospholipid syndrome. The\n                      <jats:italic>APOH<\/jats:italic>\n                      locus has been associated with anti\u2010\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI, but the causal variant and thrombotic risk implications remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a multiancestry genome\u2010wide association study of quantitative total anti\u2010\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI antibody levels in 5,969 participants from the Multi\u2010Ethnic Study of Atherosclerosis (MESA). The relationship between genetically determined anti\u2010\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI levels and venous thromboembolism (VTE) risk was evaluated using two\u2010sample Mendelian randomization and Bayesian colocalization. Candidate causal variants were prioritized by fine\u2010mapping and integrative functional genomic analyses. Molecular dynamics simulations were used to investigate the structural effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a genome\u2010wide significant association at the\n                      <jats:italic>APOH<\/jats:italic>\n                      locus (lead single\u2010nucleotide polymorphism rs1801690\u2010G, \u03b2\u00a0=\u00a00.21,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a01.08\u2009\u00d7\u200910\n                      <jats:sup>\u221210<\/jats:sup>\n                      ). Paradoxically, genetic variation at the\n                      <jats:italic>APOH<\/jats:italic>\n                      locus associated with higher anti\u2010\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI levels was associated with reduced VTE risk (\u03b2\u00a0=\u00a0\u22120.25,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a03.95\u2009\u00d7\u200910\n                      <jats:sup>\u22126<\/jats:sup>\n                      ; posterior probability for hypothesis 4 (PP4)\u00a0=\u20090.97), likely reflecting horizontal pleiotropy rather than a true protective antibody effect. Fine\u2010mapping and functional genomics prioritized the missense variant rs1801690 (W335S) as the most likely causal variant. Molecular dynamics simulations support a dual\u2010effect mechanism whereby W335S impairs phospholipid binding in domain V while increasing epitope exposure in domains I and II.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>APOH<\/jats:italic>\n                      genetic signal associated with higher anti\u2010\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI levels paradoxically reduced VTE risk, likely mediated by W335S via epitope accessibility and disrupted phospholipid binding. These findings provide human genetic evidence that phospholipid binding in domain V is essential for anti\u2010\u03b2\n                      <jats:sub>2<\/jats:sub>\n                      GPI\u2013mediated thrombosis. The clinical utility of the\n                      <jats:italic>APOH<\/jats:italic>\n                      genotype warrants further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70333","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:16:37Z","timestamp":1788837397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Coding Single\u2010Nucleotide Polymorphism in \u03b2\n                    <sub>2<\/sub>\n                    \u2010Glycoprotein I (\n                    <scp>APOH<\/scp>\n                    ) Is Associated With Increased Autoantibody Levels but Reduced Venous Thromboembolism Risk"],"prefix":"10.1002","author":[{"given":"Christophe","family":"Lalaurie","sequence":"first","affiliation":[{"name":"Department of Aging, Rheumatology, and Regenerative Medicine, Division of Medicine University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Nephrology) and Department of Computational Medicine and Bioinformatics University of Michigan  Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atlas","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Columbia University Irving Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Columbia University Irving Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3872-7793","authenticated-orcid":false,"given":"Stephen S.","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences University of Virginia  Charlottesville Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Graham","family":"Barr","sequence":"additional","affiliation":[{"name":"Division of General Medicine, Department of Medicine Columbia University Irving Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elana J.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine Columbia University Irving Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Kiryluk","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Columbia University Irving Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1712-9957","authenticated-orcid":false,"given":"Thomas","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Department of Aging, Rheumatology, and Regenerative Medicine, 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