Barral, SandraCheng, RongReitz, ChristianeVardarajan, BadriLee, JosephKunkle, BrianBeecham, GaryCantwell, Laura S.Pericak-Vance, Margaret A.Farrer, Lindsay A.Haines, Jonathan L.Goate, Alison M.Foroud, TatianaBoerwinkle, EricSchellenberg, Gerard D.Mayeux, Richard2017-06-132017-06-132015-12Barral, S., Cheng, R., Reitz, C., Vardarajan, B., Lee, J., Kunkle, B., … Mayeux, R. (2015). Linkage analyses in Caribbean Hispanic families identifies novel loci associated with familial late-onset Alzheimer’s disease. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association, 11(12), 1397–1406. http://doi.org/10.1016/j.jalz.2015.07.487https://hdl.handle.net/1805/12987INTRODUCTION: We performed linkage analyses in Caribbean Hispanic families with multiple late-onset Alzheimer's disease (LOAD) cases to identify regions that may contain disease causative variants. METHODS: We selected 67 LOAD families to perform genome-wide linkage scan. Analysis of the linked regions was repeated using the entire sample of 282 families. Validated chromosomal regions were analyzed using joint linkage and association. RESULTS: We identified 26 regions linked to LOAD (HLOD ≥3.6). We validated 13 of the regions (HLOD ≥2.5) using the entire family sample. The strongest signal was at 11q12.3 (rs2232932: HLODmax = 4.7, Pjoint = 6.6 × 10(-6)), a locus located ∼2 Mb upstream of the membrane-spanning 4A gene cluster. We additionally identified a locus at 7p14.3 (rs10255835: HLODmax = 4.9, Pjoint = 1.2 × 10(-5)), a region harboring genes associated with the nervous system (GARS, GHRHR, and NEUROD6). DISCUSSION: Future sequencing efforts should focus on these regions because they may harbor familial LOAD causative mutations.en-USPublisher PolicyCaribbean Hispanic familiesJoint linkage and associationLate-onset Alzheimer's diseaseLinkage analysisArticle