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&amp;amp; Dementia"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Recent genome\u2010wide association studies (GWAS) have reported a genetic association with Alzheimer's disease (AD) at the\n                      <jats:italic>TNIP1\/GPX3<\/jats:italic>\n                      locus, but the mechanism is unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We used cerebrospinal fluid (CSF) proteomics data to test (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0137) and replicate (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0446) the association of glutathione peroxidase 3 (GPX3) with CSF biomarkers (including amyloid and tau) and the GWAS\u2010implicated variants (rs34294852 and rs871269).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      CSF GPX3 levels decreased with amyloid and tau positivity (analysis of variance\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a01.5\u00a0\u00d7\u00a010\n                      <jats:sup>\u22125<\/jats:sup>\n                      ) and higher CSF phosphorylated tau (p\u2010tau) levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a09.28\u00a0\u00d7\u00a010\n                      <jats:sup>\u22127<\/jats:sup>\n                      ). The rs34294852 minor allele was associated with decreased GPX3 (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.041). The replication cohort found associations of GPX3 with amyloid and tau positivity (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a02.56\u00a0\u00d7\u00a010\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) and CSF p\u2010tau levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a04.38\u00a0\u00d7\u00a010\n                      <jats:sup>\u22129<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      These results suggest variants in the\n                      <jats:italic>TNIP1<\/jats:italic>\n                      locus may affect the oxidative stress response in AD via altered GPX3 levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Cerebrospinal fluid (CSF) glutathione peroxidase 3 (GPX3) levels decreased with amyloid and tau positivity and higher CSF phosphorylated tau.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The minor allele of rs34294852 was associated with lower CSF GPX3. levels when also controlling for amyloid and tau category.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>GPX3 transcript levels in the prefrontal cortex were lower in Alzheimer's disease than controls.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            rs34294852 is an expression quantitative trait locus for\n                            <jats:italic>GPX3<\/jats:italic>\n                            in blood, neutrophils, and microglia.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13848","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T13:38:41Z","timestamp":1716989921000},"page":"5044-5053","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Post\u2010GWAS multiomic functional investigation of the\n                    <i>TNIP1<\/i>\n                    locus in Alzheimer's disease highlights a potential role for GPX3"],"prefix":"10.1002","volume":"20","author":[{"given":"Daniel J.","family":"Panyard","sequence":"first","affiliation":[{"name":"Department of Genetics Stanford University School of Medicine Stanford University  Stanford California USA"},{"name":"Department of Population Health Sciences University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianne M.","family":"Reus","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc  Amsterdam The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration  Amsterdam The Netherlands"},{"name":"Center for Neurobehavioral Genetics University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Hope Center for Neurological Disorders Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Statistics University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetiva K.","family":"Deming","sequence":"additional","affiliation":[{"name":"Department of Population Health Sciences University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongshi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Statistics University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendlyn","family":"Kollmorgen","sequence":"additional","affiliation":[{"name":"Roche Diagnostics GmbH  Penzberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Carboni","sequence":"additional","affiliation":[{"name":"Roche Diagnostics International Ltd  Rotkreuz Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Wild","sequence":"additional","affiliation":[{"name":"Roche Diagnostics GmbH  Penzberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter J.","family":"Visser","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc  Amsterdam The Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration  Amsterdam The Netherlands"},{"name":"Department of Psychiatry Maastricht University  Maastricht The Netherlands"},{"name":"Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bertram","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics Institutes of Neurogenetics and Cardiogenetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Department of Psychology University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  London UK"},{"name":"UK Dementia Research Institute at UCL  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Gobom","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Western","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Hope Center for Neurological Disorders Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Ju","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Hope Center for Neurological Disorders Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M.","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"William S. Middleton Memorial Veterans Hospital  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling C.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"William S. Middleton Memorial Veterans Hospital  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Asthana","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"William S. 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