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However, much of AD\u2019s heritability remains unexplained; as the prevalence of AD varies across populations, the genetic architecture of the disease may also vary by population with the presence of novel variants or loci.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted genome-wide analyses of AD in a sample of 2565 Caribbean Hispanics to better understand the genetic contribution to AD in this population. Statistical analysis included both admixture mapping and association testing. Evidence for differential gene expression within regions of interest was collected from independent transcriptomic studies comparing AD cases and controls in samples with primarily European ancestry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Our genome-wide association study of AD identified no loci reaching genome-wide significance. However, a genome-wide admixture mapping analysis that tests for association between a haplotype\u2019s ancestral origin and AD status detected a genome-wide significant association with chromosome 3q13.11 (103.7\u2013107.7Mb, <jats:italic>P<\/jats:italic> = 8.76E\u221207), driven by a protective effect conferred by the Native American ancestry (OR = 0.58, 95%CI = 0.47\u22120.73). Within this region, two variants were significantly associated with AD after accounting for the number of independent tests (rs12494162, <jats:italic>P<\/jats:italic> = 2.33E\u221206; rs1731642, <jats:italic>P<\/jats:italic> = 6.36E\u221205). The significant admixture mapping signal is composed of 15 haplotype blocks spanning 5 protein-coding genes (<jats:italic>ALCAM<\/jats:italic>, <jats:italic>BBX<\/jats:italic>, <jats:italic>CBLB<\/jats:italic>, <jats:italic>CCDC54<\/jats:italic>, <jats:italic>CD47<\/jats:italic>) and four brain-derived topologically associated domains, and includes markers significantly associated with the expression of <jats:italic>ALCAM<\/jats:italic>, <jats:italic>BBX<\/jats:italic>, <jats:italic>CBLB<\/jats:italic>, and <jats:italic>CD47<\/jats:italic> in the brain. <jats:italic>ALCAM<\/jats:italic> and <jats:italic>BBX<\/jats:italic> were also significantly differentially expressed in the brain between AD cases and controls with European ancestry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These results provide multiethnic evidence for a relationship between AD and multiple genes at 3q13.11 and illustrate the utility of leveraging genetic ancestry diversity via admixture mapping for new insights into AD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13195-021-00866-9","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T18:02:52Z","timestamp":1625335372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Admixture mapping reveals the association between Native American ancestry at 3q13.11 and reduced risk of Alzheimer\u2019s disease in Caribbean Hispanics"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8573-5158","authenticated-orcid":false,"given":"Andr\u00e9a R. 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