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Rare coding variants found in at least 2 data sets were genotyped in independent groups of ancestry\u2010matched controls. Additionally, the Exome Aggregation Consortium was used as a reference data set for population\u2010based allele frequencies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall we detected a statistically significant 3.1\u2010fold enrichment of the nonsynonymous mutations in the Caucasian LOAD cases compared with controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.002) and no difference in synonymous variants. A stop\u2010gain mutation in <jats:italic>ABCA7<\/jats:italic> (E1679X) and missense mutation in <jats:italic>CD2AP<\/jats:italic> (K633R) were highly significant in Caucasian LOAD cases, and mutations in <jats:italic>EPHA1<\/jats:italic> (P460L) and <jats:italic>BIN1<\/jats:italic> (K358R) were significant in Caribbean Hispanic families with LOAD. The <jats:italic>EPHA1<\/jats:italic> variant segregated completely in an extended Caribbean Hispanic family and was also nominally significant in the Caucasians. Additionally, <jats:italic>BIN1<\/jats:italic> (K358R) segregated in 2 of the 6 Caribbean Hispanic families where the mutations were discovered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Targeted sequencing of confirmed GWAS loci revealed an excess burden of deleterious coding mutations in LOAD, with the greatest burden observed in <jats:italic>ABCA7<\/jats:italic> and <jats:italic>BIN1<\/jats:italic>. Identifying coding variants in LOAD will facilitate the creation of tractable models for investigation of disease\u2010related mechanisms and potential therapies. Ann Neurol 2015;78:487\u2013498<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24466","type":"journal-article","created":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T16:12:26Z","timestamp":1435075946000},"page":"487-498","source":"Crossref","is-referenced-by-count":146,"title":["Rare coding mutations identified by sequencing of <scp>A<\/scp>lzheimer disease genome\u2010wide association studies loci"],"prefix":"10.1002","volume":"78","author":[{"given":"Badri N.","family":"Vardarajan","sequence":"first","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center New York NY"},{"name":"Gertrude H. 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