@article{8ac18f9009de42f7af5c4bb0a6a65e5f,
title = "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.",
keywords = "Admixture mapping, African-American, Alzheimer's disease, Genome-wide association analysis (GWAS), Local admixture, Local ancestry",
author = "{Alzheimer Disease Genetics Consortium} and Hohman, {Timothy J.} and Cooke-Bailey, {Jessica N.} and Christiane Reitz and Gyungah Jun and Adam Naj and Beecham, {Gary W.} and Zhi Liu and Carney, {Regina M.} and Vance, {Jeffrey M.} and Cuccaro, {Michael L.} and Ruchita Rajbhandary and Vardarajan, {Badri Narayan} and Wang, {Li San} and Otto Valladares and Lin, {Chiao Feng} and Larson, {Eric B.} and Graff-Radford, {Neill R.} and Denis Evans and {De Jager}, {Philip L.} and Crane, {Paul K.} and Buxbaum, {Joseph D.} and Murrell, {Jill R.} and Towfique Raj and Nilufer Ertekin-Taner and Logue, {Mark W.} and Baldwin, {Clinton T.} and Green, {Robert C.} and Barnes, {Lisa L.} and Cantwell, {Laura B.} and Fallin, {M. Daniele} and Go, {Rodney C.P.} and Patrick Griffith and Obisesan, {Thomas O.} and Manly, {Jennifer J.} and Lunetta, {Kathryn L.} and Kamboh, {M. Ilyas} and Lopez, {Oscar L.} and Bennett, {David A.} and John Hardy and Hendrie, {Hugh C.} and Hall, {Kathleen S.} and Goate, {Alison M.} and Rosalyn Lang and Byrd, {Goldie S.} and Kukull, {Walter A.} and Foroud, {Tatiana M.} and Farrer, {Lindsay A.} and Martin, {Eden R.} and Pericak-Vance, {Margaret A.} and Schellenberg, {Gerard D.}",
note = "Funding Information: Acknowledgments The authors report no conflicts of interest. This research was supported in part by the Pharmaceutical Research and Manufacturers of America Foundation Fellowship in Translational Medicine and Therapeutics and T32 MH65215 and K12 HD043483 (T.J.H.), P30 AG036445 (T.A.T.-W.), T32 EY21453-2 and T32 EY007157 (J.N.C.-B.), and K23AG034550, KL2RR024151, P30AG019610, R01A G030653, R01AG031581, R01AG15819, R01AG17917, R01AG222018, R01AG30146, R01AG032990, R01A G009029, R01CA129769, R01MH080295, R01AG017173, R01AG025259, R01AG020688, R01AG028786, R01AG 037212, R01AG1101, R01AG33193, R01AG026916, R01AG019085, R01AG030653, R01AG041718, R01AG 009956, R01AG027944, R01AG021547, R01AG019757, RC2AG036650, RC2AG036528, R37AG015473, P01AG 026276, P01AG03991, P01AG019724, P01AG010491, P01AG002219, P20MD000546, P30AG010129, P30AG 028383, P30AG010124, P30AG012300, P30AG028377, P30AG10133, P30AG08051, P30AG013854, P30AG 008017, P30AG10161, P30AG13846, P50AG005133, P50AG016582, P50AG005681, P50AG016574, P50AG 005138, P50AG016573, P50AG016575, P50AG016576, P50AG016577, P50AG016570, P50AG005131, P50AG 023501, P50AG008671, P50AG005142, P50AG005146, P50AG005134, P50AG008702, P50AG005136, P50AG 05128, P50AG025688, MO1RR00096, UL1RR029893, UL1RR02777, U01AG10483, U24AG026390, U24AG 026395, U24AG021886, U01AG016976, U01HG006375, U01AG06781, U01HG004610, and U01AG032984 (Alzheimer Disease Genetics Consortium [ADGC]). We thank Creighton Phelps, Stephen Snyder, and Marilyn Miller from the NIA, who are exfficio members of the ADGC. Support was also provided by the Alzheimer's Association (IIRG-08-89720 and IIRG-05-14147), National Institute of Neurological Disorders and Stroke grant P50NS39764, National Institute of Mental Health grant P50MH60451, GlaxoSmithKline, and the Office of Research and Development, Biomedical Laboratory Research Program, US Department of Veterans Affairs Administration. For the ADGC, biological samples and associated phenotypic data used in primary data analyses were stored at principal investigators' institutions and at the National Cell Repository for Alzheimer's Disease (NCRAD) at Indiana University, funded by the NIA (U24AG02188). Associated phenotypic data used in secondary data analyses were stored at the National Alzheimer's Coordinating Center and at the NIA Alzheimer's Disease Data Storage Site at the University of Pennsylvania, funded by the NIA. Contributors to the genetic analysis data included principal investigators on projects individually funded by the NIA, other NIH institutes, or private entities. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: C.T.B. reported serving as a consultant for the Center for Human Genetics Inc. R.C.P.G. reported receiving travel support from the National Institutes of Health (NIH). P.G. reported receiving payment for lectures from Eisai and Pfizer. J.J.M. reported serving as a board member for the International Neuropsychological Society; receiving grants or grants pending from the Alzheimer's Association and the National Institute on Aging (NIA); and receiving travel expenses from the Alzheimer's Association. O.L.L. reported receiving consulting fees or honoraria from Mertz and Lundbeck. D.A.B. reported receiving travel support from the NIH. A.M.G. reported serving as a consultant for Finnegan; providing expert testimony in cases involving the genetics of Alzheimer disease; receiving grants or grants pending from Genentech and Pfizer; receiving payment for lectures from Pfizer, Genentech, and Amgen; and receiving patent royalties from Taconic for a tau mutation. M.A.P.-V. reported receiving revenues from Athena Diagnostics. No other authors reported disclosures. Funding Information: The authors report no conflicts of interest. This research was supported in part by the Pharmaceutical Research and Manufacturers of America Foundation Fellowship in Translational Medicine and Therapeutics and T32 MH65215 and K12 HD043483 (T.J.H.), P30 AG036445 (T.A.T.-W.), T32 EY21453-2 and T32 EY007157 (J.N.C.-B.), and K23AG034550 , KL2RR024151 , P30AG019610 , R01AG030653 , R01AG031581 , R01AG15819 , R01AG17917 , R01AG222018 , R01AG30146 , R01AG032990 , R01AG009029 , R01CA129769 , R01MH080295 , R01AG017173 , R01AG025259 , R01AG020688 , R01AG028786 , R01AG037212 , R01AG1101 , R01AG33193 , R01AG026916 , R01AG019085 , R01AG030653 , R01AG041718 , R01AG009956 , R01AG027944 , R01AG021547 , R01AG019757 , RC2AG036650 , RC2AG036528 , R37AG015473 , P01AG026276 , P01AG03991 , P01AG019724 , P01AG010491 , P01AG002219 , P20MD000546 , P30AG010129 , P30AG028383 , P30AG010124 , P30AG012300 , P30AG028377 , P30AG10133 , P30AG08051 , P30AG013854 , P30AG008017 , P30AG10161 , P30AG13846 , P50AG005133 , P50AG016582 , P50AG005681 , P50AG016574 , P50AG005138 , P50AG016573 , P50AG016575 , P50AG016576 , P50AG016577 , P50AG016570 , P50AG005131 , P50AG023501 , P50AG008671 , P50AG005142 , P50AG005146 , P50AG005134 , P50AG008702 , P50AG005136 , P50AG05128 , P50AG025688 , MO1RR00096 , UL1RR029893 , UL1RR02777 , U01AG10483 , U24AG026390 , U24AG026395 , U24AG021886 , U01AG016976 , U01HG006375 , U01AG06781 , U01HG004610 , and U01AG032984 (Alzheimer Disease Genetics Consortium [ADGC]). We thank Creighton Phelps, Stephen Snyder, and Marilyn Miller from the NIA, who are ex-officio members of the ADGC. Support was also provided by the Alzheimer's Association ( IIRG-08-89720 and IIRG-05-14147 ), National Institute of Neurological Disorders and Stroke grant P50NS39764 , National Institute of Mental Health grant P50MH60451 , GlaxoSmithKline , and the Office of Research and Development , Biomedical Laboratory Research Program, US Department of Veterans Affairs Administration . For the ADGC, biological samples and associated phenotypic data used in primary data analyses were stored at principal investigators' institutions and at the National Cell Repository for Alzheimer's Disease (NCRAD) at Indiana University, funded by the NIA ( U24AG02188 ). Associated phenotypic data used in secondary data analyses were stored at the National Alzheimer's Coordinating Center and at the NIA Alzheimer's Disease Data Storage Site at the University of Pennsylvania, funded by the NIA. Contributors to the genetic analysis data included principal investigators on projects individually funded by the NIA, other NIH institutes, or private entities. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2016 The Alzheimer's Association.",
year = "2016",
month = mar,
day = "1",
doi = "10.1016/j.jalz.2015.02.012",
language = "English (US)",
volume = "12",
pages = "233--243",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "3",
}
