{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:22:37Z","timestamp":1790220157683,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,1,7]],"date-time":"2018-01-07T00:00:00Z","timestamp":1515283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0400074"],"award-info":[{"award-number":["G0400074"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2018,8]]},"abstract":"\n Aim<\/jats:title>\n \n Late\u2010onset Alzheimer's disease (\n LOAD<\/jats:styled-content>\n ) accounts for 95% of all Alzheimer's cases and is genetically complex in nature. Overlapping clinical and neuropathological features between\n AD<\/jats:styled-content>\n ,\n FTD<\/jats:styled-content>\n and Parkinson's disease highlight the potential role of genetic pleiotropy across diseases. Recent genome\u2010wide association studies (\n GWAS<\/jats:styled-content>\n s) have uncovered 20 new loci for\n AD<\/jats:styled-content>\n risk; however, these exhibit small effect sizes. Using\n NGS<\/jats:styled-content>\n , here we perform association analyses using exome\u2010wide and candidate\u2010gene\u2010driven approaches.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Whole\u2010exome sequencing was performed on 132\n AD<\/jats:styled-content>\n cases and 53 control samples. Exome\u2010wide single\u2010variant association and gene burden tests were performed for 76\u00a0640 nonsingleton variants. Samples were also screened for known causative mutations in familial genes in\n AD<\/jats:styled-content>\n and other dementias. Single\u2010variant association and burden analysis was also carried out on variants in known\n AD<\/jats:styled-content>\n and other neurological dementia genes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Tentative single\u2010variant and burden associations were seen in several genes with kinase and protease activity. Exome\u2010wide burden analysis also revealed significant burden of variants in\n \n PILRA<\/jats:styled-content>\n <\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0=\u00a03.4\u00a0\u00d7\u00a010\n \u22125<\/jats:sup>\n ), which has previously been linked to\n AD<\/jats:styled-content>\n via\n GWAS<\/jats:styled-content>\n , hit\n \n ZCWPW<\/jats:styled-content>\n 1\n <\/jats:italic>\n . Screening for causative mutations in familial\n AD<\/jats:styled-content>\n and other dementia genes revealed no pathogenic variants. Variants identified in\n \n ABCA<\/jats:styled-content>\n 7\n <\/jats:italic>\n ,\n \n SLC<\/jats:styled-content>\n 24A4\n <\/jats:italic>\n ,\n \n CD<\/jats:styled-content>\n 33\n <\/jats:italic>\n and\n \n LRRK<\/jats:styled-content>\n 2\n <\/jats:italic>\n were nominally associated with disease (\n P<\/jats:italic>\n \u00a0<\u00a00.05) but did not withstand correction for multiple testing.\n \n APOE<\/jats:styled-content>\n <\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0=\u00a00.02) and\n \n CLU<\/jats:styled-content>\n <\/jats:italic>\n (\n P<\/jats:italic>\n \u00a0=\u00a00.04) variants showed significant burden on\n AD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In addition, polygenic risk scores (\n PRS<\/jats:styled-content>\n ) were able to distinguish between cases and controls with 83.8% accuracy using 3268 variants, sex, age at death and\n \n APOE<\/jats:styled-content>\n <\/jats:italic>\n \u03b54 and \u03b52 status as predictors.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nan.12452","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T21:37:37Z","timestamp":1511818657000},"page":"506-521","source":"Crossref","is-referenced-by-count":46,"title":["Whole\u2010exome sequencing of the\n BDR<\/scp>\n cohort: evidence to support the role of the\n \n PILRA<\/scp>\n <\/i>\n gene in Alzheimer's disease"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-1443","authenticated-orcid":false,"given":"T.","family":"Patel","sequence":"first","affiliation":[{"name":"Human Genetics Group University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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