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Age at onset (\n AAO<\/jats:styled-content>\n ) of\n AD<\/jats:styled-content>\n is an important component phenotype with a genetic basis, and identification of genes in which variation affects\n AAO<\/jats:styled-content>\n would contribute to identification of factors that affect timing of onset. Increase in\n AAO<\/jats:styled-content>\n through prevention or therapeutic measures would have enormous benefits by delaying\n AD<\/jats:styled-content>\n and its associated morbidities. In this paper, we performed a family\u2010based genome\u2010wide association study for\n AAO<\/jats:styled-content>\n of late\u2010onset\n AD<\/jats:styled-content>\n in whole exome sequence data generated in multigenerational families with multiple\n AD<\/jats:styled-content>\n cases. We conducted single marker and gene\u2010based burden tests for common and rare variants, respectively. We combined association analyses with variance component linkage analysis, and with reference to prior studies, in order to enhance evidence of the identified genes. For variants and genes implicated by the association study, we performed a gene\u2010set enrichment analysis to identify potential novel pathways associated with\n AAO<\/jats:styled-content>\n of\n AD<\/jats:styled-content>\n . We found statistically significant association with\n AAO<\/jats:styled-content>\n for three genes (\n \n WRN<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n NTN4<\/jats:styled-content>\n <\/jats:italic>\n and\n \n LAMC3<\/jats:styled-content>\n <\/jats:italic>\n ) with common associated variants, and for four genes (\n \n SLC8A3<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n SLC19A3<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n MADD<\/jats:styled-content>\n <\/jats:italic>\n and\n \n LRRK2<\/jats:styled-content>\n <\/jats:italic>\n ) with multiple rare\u2010associated variants that have a plausible biological function related to\n AD<\/jats:styled-content>\n . The genes we have identified are in pathways that are strong candidates for involvement in the development of\n AD<\/jats:styled-content>\n pathology and may lead to a better understanding of\n AD<\/jats:styled-content>\n pathogenesis.\n <\/jats:p>","DOI":"10.1111\/gbb.12250","type":"journal-article","created":{"date-parts":[[2015,9,3]],"date-time":"2015-09-03T06:46:10Z","timestamp":1441262770000},"page":"607-617","source":"Crossref","is-referenced-by-count":19,"title":["Family\u2010based genome scan for age at onset of late\u2010onset Alzheimer's disease in whole exome sequencing data"],"prefix":"10.1111","volume":"14","author":[{"given":"M.","family":"Saad","sequence":"first","affiliation":[{"name":"Department of Biostatistics University of Washington Seattle WA USA"},{"name":"Division of Medical Genetics, Department of Medicine University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Brkanac","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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