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Title | Characterizing Clinical and Neuropathological Traits of APOE Haplotypes in African Americans and Europeans. |
Publication Type | Journal Article |
Authors | Mezlini AM, Magdamo C, Merrill E, Chibnik LB, Blacker DL, Hyman BT, Das S |
Journal | J Alzheimers Dis |
Volume | 78 |
Issue | 1 |
Pagination | 467-477 |
Date Published | 2020 |
ISSN | 1875-8908 |
Abstract | BACKGROUND: The APOEɛ4 allele is the largest genetic risk factor for late-onset Alzheimer's disease (AD). Recent literature suggested that the contribution of APOEɛ4 to AD risk could be population-specific, with ɛ4 conferring a lower risk to Blacks or African Americans. OBJECTIVE: To investigate the effect of APOE haplotypes on AD risk in individuals with European ancestry (EU) and Blacks or African Americans (AA). METHODS: We selected data from 1) the National Alzheimer's Coordinating Center: a total of 3,486 AD cases and 4,511 controls (N = 7,997, 60% female) with genotypes from the Alzheimer's Disease Genetics Consortium (ADGC), and 2) the Rush University Religious Orders Study and Memory and Aging Project (ROSMAP) cohort with 578 AD and 670 controls (N = 1,248, 60% female). Using ɛ3 homozygotes as the reference, we compared the association of various APOE haplotypes with the clinical and neuropathological correlates of dementia in AA and EU. RESULTS: In both cohorts, we find no difference in the odds or age of onset of AD among the ɛ4-linked haplotypes defined by rs769449 within either AA or EU. Additionally, while APOEɛ4 was associated with a faster rate of decline, no differences were found in rate of decline, clinical or neuropathological features among the ɛ4-linked haplotypes. Further analysis with other variants near the APOE locus failed to identify any effect modification. CONCLUSION: Our study finds similar effects of the ɛ4-linked haplotypes defined by rs769449 on AD as compared to ɛ3 in both AA and EU. Future studies are required to understand the heterogeneity of APOE conferred risk of AD among various genotypes and populations. |
DOI | 10.3233/JAD-200228 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 33016904 |
PubMed Central ID | PMC7774865 |
Grant List | P30 AG062421 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States RC2 AG036528 / AG / NIA NIH HHS / United States P30 AG019610 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States P30 AG062428 / AG / NIA NIH HHS / United States P50 AG008702 / AG / NIA NIH HHS / United States P50 AG025688 / AG / NIA NIH HHS / United States P50 AG047266 / AG / NIA NIH HHS / United States P30 AG010133 / AG / NIA NIH HHS / United States P50 AG005146 / AG / NIA NIH HHS / United States P30 AG062421 / AG / NIA NIH HHS / United States P30 AG062422 / AG / NIA NIH HHS / United States P50 AG005138 / AG / NIA NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States P30 AG013854 / AG / NIA NIH HHS / United States P30 AG008017 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States P50 AG047366 / AG / NIA NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States P50 AG016573 / AG / NIA NIH HHS / United States P30 AG062429 / AG / NIA NIH HHS / United States P50 AG023501 / AG / NIA NIH HHS / United States P30 AG035982 / AG / NIA NIH HHS / United States P30 AG028383 / AG / NIA NIH HHS / United States P30 AG053760 / AG / NIA NIH HHS / United States P30 AG010124 / AG / NIA NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States P50 AG005142 / AG / NIA NIH HHS / United States P30 AG012300 / AG / NIA NIH HHS / United States P30 AG049638 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States P30 AG062715 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States P50 AG047270 / AG / NIA NIH HHS / United States |