Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk.

Alzheimers Dement
Authors
Keywords
Abstract

INTRODUCTION: African-American (AA) individuals have a higher risk for late-onset Alzheimer's disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the Alzheimer's disease (AD)-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7) differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered.

METHODS: We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status.

RESULTS: Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences.

DISCUSSION: Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.

Year of Publication
2016
Journal
Alzheimers Dement
Volume
12
Issue
3
Pages
233-43
Date Published
2016 Mar
ISSN
1552-5279
DOI
10.1016/j.jalz.2015.02.012
PubMed ID
26092349
PubMed Central ID
PMC4681680
Links
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P30 AG013854 / AG / NIA NIH HHS / United States
P30AG012300 / AG / NIA NIH HHS / United States
P50 MH060451 / MH / NIMH NIH HHS / United States
P50AG016570 / AG / NIA NIH HHS / United States
P30AG028383 / AG / NIA NIH HHS / United States
U01AG10483 / AG / NIA NIH HHS / United States
P50AG005133 / AG / NIA NIH HHS / United States
UL1 TR001445 / TR / NCATS NIH HHS / United States
P30AG010129 / AG / NIA NIH HHS / United States
R01AG019085 / AG / NIA NIH HHS / United States
P30 AG010124 / AG / NIA NIH HHS / United States
P01AG026276 / AG / NIA NIH HHS / United States
P50 AG023501 / AG / NIA NIH HHS / United States
R01AG025259 / AG / NIA NIH HHS / United States
U01 HG006375 / HG / NHGRI NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
U01HG006375 / HG / NHGRI NIH HHS / United States
P30 AG028377 / AG / NIA NIH HHS / United States
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RF1 AG015819 / AG / NIA NIH HHS / United States
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U24AG026395 / AG / NIA NIH HHS / United States
P50AG005134 / AG / NIA NIH HHS / United States
R01AG009029 / AG / NIA NIH HHS / United States
R01AG021547 / AG / NIA NIH HHS / United States
P30 AG028383 / AG / NIA NIH HHS / United States
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