1. Linkage analyses in Caribbean Hispanic families identify novel loci associated with familial late-onset Alzheimer's disease.
- Author
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Barral S, Cheng R, Reitz C, Vardarajan B, Lee J, Kunkle B, Beecham G, Cantwell LS, Pericak-Vance MA, Farrer LA, Haines JL, Goate AM, Foroud T, Boerwinkle E, Schellenberg GD, and Mayeux R
- Subjects
- Aged, Aged, 80 and over, Chromosome Mapping methods, Dominican Republic ethnology, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, New York City, Puerto Rico ethnology, Alzheimer Disease genetics, Genetic Linkage, Hispanic or Latino genetics, Polymorphism, Single Nucleotide
- Abstract
Introduction: 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., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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