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


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.

SUBMITTER: Hohman TJ 

PROVIDER: S-EPMC4681680 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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

Hohman Timothy J TJ   Cooke-Bailey Jessica N JN   Reitz Christiane C   Jun Gyungah G   Naj Adam A   Beecham Gary W GW   Liu Zhi Z   Carney Regina M RM   Vance Jeffrey M JM   Cuccaro Michael L ML   Rajbhandary Ruchita R   Vardarajan Badri Narayan BN   Wang Li-San LS   Valladares Otto O   Lin Chiao-Feng CF   Larson Eric B EB   Graff-Radford Neill R NR   Evans Denis D   De Jager Philip L PL   Crane Paul K PK   Buxbaum Joseph D JD   Murrell Jill R JR   Raj Towfique T   Ertekin-Taner Nilufer N   Logue Mark W MW   Baldwin Clinton T CT   Green Robert C RC   Barnes Lisa L LL   Cantwell Laura B LB   Fallin M Daniele MD   Go Rodney C P RC   Griffith Patrick P   Obisesan Thomas O TO   Manly Jennifer J JJ   Lunetta Kathryn L KL   Kamboh M Ilyas MI   Lopez Oscar L OL   Bennett David A DA   Hardy John J   Hendrie Hugh C HC   Hall Kathleen S KS   Goate Alison M AM   Lang Rosalyn R   Byrd Goldie S GS   Kukull Walter A WA   Foroud Tatiana M TM   Farrer Lindsay A LA   Martin Eden R ER   Pericak-Vance Margaret A MA   Schellenberg Gerard D GD   Mayeux Richard R   Haines Jonathan L JL   Thornton-Wells Tricia A TA  

Alzheimer's & dementia : the journal of the Alzheimer's Association 20150616 3


<h4>Introduction</h4>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.  ...[more]

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