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Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (A\u03b2) deposits in the brain and to study Alzheimer\u2019s disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N\u2009=\u200913,409)\u00a0to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong <jats:italic>APOE<\/jats:italic> signal on chr19q.13.32 (top SNP: <jats:italic>APOE<\/jats:italic> \u025b4; rs429358; \u03b2\u2009=\u20090.35, SE\u2009=\u20090.01, P\u2009=\u20096.2\u2009\u00d7\u200910<jats:sup>\u2013311<\/jats:sup>, MAF\u2009=\u20090.19), driven by <jats:italic>APOE<\/jats:italic> \u025b4, and five additional novel associations (<jats:italic>APOE<\/jats:italic> \u03b52\/rs7412; rs73052335\/rs5117, rs1081105, rs438811, and rs4420638) independent of <jats:italic>APOE<\/jats:italic> \u025b4. <jats:italic>APOE<\/jats:italic> \u025b4 and \u03b52 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the <jats:italic>APOE<\/jats:italic>, we also identified three other genome-wide loci: <jats:italic>ABCA7<\/jats:italic> (rs12151021\/chr19p.13.3; \u03b2\u2009=\u20090.07, SE\u2009=\u20090.01, <jats:italic>P<\/jats:italic>\u2009=\u20099.2\u2009\u00d7\u200910<jats:sup>\u201309<\/jats:sup>, MAF\u2009=\u20090.32), <jats:italic>CR1<\/jats:italic> (rs6656401\/chr1q.32.2; \u03b2\u2009=\u20090.1, SE\u2009=\u20090.02, P\u2009=\u20092.4\u2009\u00d7\u200910<jats:sup>\u201310<\/jats:sup>, MAF\u2009=\u20090.18) and <jats:italic>FERMT2<\/jats:italic> locus (rs117834516\/chr14q.22.1; \u03b2\u2009=\u20090.16, SE\u2009=\u20090.03, <jats:italic>P<\/jats:italic>\u2009=\u20091.1\u2009\u00d7\u200910<jats:sup>\u201309<\/jats:sup>, MAF\u2009=\u20090.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, \u03b2\u2009=\u20090.79, SE\u2009=\u20090.14, P\u2009=\u20091.4\u2009\u00d7\u200910<jats:sup>\u201308<\/jats:sup>, MAF\u2009=\u20090.006, sex-interaction P\u2009=\u20099.8\u2009\u00d7\u200910<jats:sup>\u201307<\/jats:sup>) and chr11p.15.2 (rs192346166, \u03b2\u2009=\u20090.94, SE\u2009=\u20090.17, P\u2009=\u20093.7\u2009\u00d7\u200910<jats:sup>\u201308<\/jats:sup>, MAF\u2009=\u20090.004, sex-interaction P\u2009=\u20091.3\u2009\u00d7\u200910<jats:sup>\u201303<\/jats:sup>). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.<\/jats:p>","DOI":"10.1186\/s40478-023-01563-4","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T17:02:38Z","timestamp":1682528558000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease"],"prefix":"10.1186","volume":"11","author":[{"given":"Muhammad","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek B.","family":"Archer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Gorijala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Western","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jigyasha","family":"Timsina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia L.","family":"Satizabal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa S.","family":"Beiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengsheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammie L. 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