{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:00:04Z","timestamp":1790773204983,"version":"4.1.0"},"reference-count":29,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Institute of Aging","award":["U01 AG058589"],"award-info":[{"award-number":["U01 AG058589"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Identifying genetic variants conferring resilience to Alzheimer's disease and related dementia (ADRD) may hold promise for developing therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine genetic associations with being dementia-free at age 85 (DF85).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined genetic associations, using whole genome sequencing data, with DF85 in three Trans-Omics for Precision Medicine cohorts and the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium. We tested common variants individually and aggregation of rare (MAF\u2009\u2264\u20091%) coding and non-coding variants in DF85 participants (n\u2009=\u20093657) against individuals who were not DF85 (n\u2009=\u200920,010). We verified associations using a stricter control set who developed dementia before age 85 (n\u2009=\u20095552).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed an association at\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      (rs429358, MAF\u2009=\u20090.21, odds ratio [OR]\u2009=\u20090.49, 95% confidence interval [CI]\u2009=\u20090.46\u20130.53, p\u2009=\u20091.0\u2009\u00d7\u200910\n                      <jats:sup>\u221292<\/jats:sup>\n                      ) as well as for two common variants (rs16892237-A near\n                      <jats:italic toggle=\"yes\">MAL2<\/jats:italic>\n                      , MAF\u2009=\u20090.08, OR\u2009=\u20091.34, 95% CI\u2009=\u20091.21\u20131.48, p\u2009=\u20091.1\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      and rs8004018-G near\n                      <jats:italic toggle=\"yes\">GCH1<\/jats:italic>\n                      , MAF\u2009=\u20090.16, OR\u2009=\u20091.24, 95% CI\u2009=\u20091.15\u20131.34, p\u2009=\u20091.7\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      ) and an aggregate of rare loss of function and disruptive missense variants in\n                      <jats:italic toggle=\"yes\">FBXW10<\/jats:italic>\n                      on chr 17 (p\u2009=\u20091.4\u2009\u00d7\u200910\n                      <jats:sup>\u22127<\/jats:sup>\n                      ) associated with DF85.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Through a genome-wide assessment of a resilience-focused outcome, we identified common and rare genetic variants contributing to DF85 status. Genes associated with DF85 may delay onset of ADRD and provide translational impact.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261444302","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:28:37Z","timestamp":1776954517000},"page":"1772-1782","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole genome sequencing analysis of over 3500 individuals dementia-free over 85 years old"],"prefix":"10.1177","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-8636","authenticated-orcid":false,"given":"Gina M.","family":"Peloso","sequence":"first","affiliation":[{"name":"Boston University School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1317-2739","authenticated-orcid":false,"given":"Dongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina M.","family":"Abbruzzese","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Bis","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-3190","authenticated-orcid":false,"given":"Seung Hoan","family":"Choi","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-7778","authenticated-orcid":false,"given":"Alexa","family":"Beiser","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Bressler","sequence":"additional","affiliation":[{"name":"Human Genetics Center, Department of Epidemiology, The University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9e","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"},{"name":"Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montr\u00e9al, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4231-3331","authenticated-orcid":false,"given":"Alison E.","family":"Fohner","sequence":"additional","affiliation":[{"name":"University of Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9476-7143","authenticated-orcid":false,"given":"Mohsen","family":"Ghanbari","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Heard-Costa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Boston University and the NHLBI's Framingham Heart Study, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Lacaze","sequence":"additional","affiliation":[{"name":"Monash University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9299-0747","authenticated-orcid":false,"given":"Quentin","family":"Le Grand","sequence":"additional","affiliation":[{"name":"University of Bordeaux, INSERM, Bordeaux Population Health research center, UMR1219, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar L.","family":"Lopez","sequence":"additional","affiliation":[{"name":"University of Pittsburgh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Mosley","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5858-3788","authenticated-orcid":false,"given":"Moeen","family":"Riaz","sequence":"additional","affiliation":[{"name":"Monash University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A\u00efcha","family":"Soumar\u00e9","sequence":"additional","affiliation":[{"name":"University of Bordeaux, INSERM, Bordeaux Population Health research center, UMR1219, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3579-8054","authenticated-orcid":false,"given":"Amber","family":"Yaqub","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Boerwinkle","sequence":"additional","affiliation":[{"name":"Human Genetics Center, Department of Epidemiology, The University of Texas Health Science Center at Houston, Houston, TX, USA"},{"name":"Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce M.","family":"Psaty","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington"},{"name":"University of Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Fornage","sequence":"additional","affiliation":[{"name":"Human Genetics Center, Department of Epidemiology, The University of Texas Health Science Center at Houston, Houston, TX, USA"},{"name":"Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"TOPMed Neurocognitive Working Group, The Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI), Alzheimer\u2019s Disease Sequencing Project","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at San Antonio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9335-2819","authenticated-orcid":false,"given":"Anita L","family":"DeStefano","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health"},{"name":"Department of Neurology, Boston University Chobanian &amp; Avedisian School of Medicine, Boston, MA, USA"},{"name":"Boston University and the NHLBI's Framingham Heart Study, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.03.001"},{"key":"e_1_3_3_3_2","article-title":"Apolipoprotein E: risk factor for Alzheimer disease","volume":"54","author":"Tsai MS","year":"1994","unstructured":"Tsai MS, Tangalos EG, Petersen RC, et al. Apolipoprotein E: risk factor for Alzheimer disease. Am J Hum Genet 1994; 54: 643\u2013639.","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01024-z"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0358-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14283"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes13010122"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.022"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa209"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504327"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1159\/000067110"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2015.12.002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03205-y"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz216"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2018.05.004"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac966"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz567"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyab044"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01641-w"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01640-x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0676-4"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100155"},{"key":"e_1_3_3_25_2","first-page":"100574","article-title":"Application of the STAAR Framework in detecting rare variant associations with Alzheimer's disease and related dementias: insights and implications","volume":"7","author":"Wang D","year":"2026","unstructured":"Wang D, Abbruzzese S, Heard-Costa N, et al. Application of the STAAR Framework in detecting rare variant associations with Alzheimer's disease and related dementias: insights and implications. HGG Adv 2026; 7: 100574.","journal-title":"HGG Adv"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00981"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.09.008"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715554115"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-022-01050-z"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01225-6"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261444302","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13872877261444302","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13872877261444302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:29:11Z","timestamp":1790771351000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13872877261444302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1177\/13872877261444302"],"URL":"https:\/\/doi.org\/10.1177\/13872877261444302","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}