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Linkage analyses in Caribbean Hispanic families identify novel loci associated with familial late-onset Alzheimer's disease.

TitleLinkage analyses in Caribbean Hispanic families identify novel loci associated with familial late-onset Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsBarral 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
Secondary AuthorsMayeux R
JournalAlzheimers Dement
Volume11
Issue12
Pagination1397-1406
Date Published2015 Dec
ISSN1552-5279
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Chromosome Mapping, Dominican Republic, Female, Genetic Linkage, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic Americans, Humans, Male, Middle Aged, New York City, Polymorphism, Single Nucleotide, Puerto Rico
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.

DOI10.1016/j.jalz.2015.07.487
Alternate JournalAlzheimers Dement
PubMed ID26433351
PubMed Central IDPMC4690771
Grant ListU24 AG021886 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
U24 AG056270 / AG / NIA NIH HHS / United States
UF1 AG047133 / AG / NIA NIH HHS / United States
R37AG015473 / AG / NIA NIH HHS / United States
UL1 TR001108 / TR / NCATS NIH HHS / United States
R01 AG015473 / AG / NIA NIH HHS / United States
R01-AG025259 / AG / NIA NIH HHS / United States
K23AG034550 / AG / NIA NIH HHS / United States
UO1AG032984 / AG / NIA NIH HHS / United States
U24 AG026395 / AG / NIA NIH HHS / United States
R01 AG041797 / AG / NIA NIH HHS / United States
R01 AG037212 / AG / NIA NIH HHS / United States
RF1 AG015473 / AG / NIA NIH HHS / United States
P30-AG13846 / AG / NIA NIH HHS / United States
5P50AG008702-25 / AG / NIA NIH HHS / United States