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Title | Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Hohman TJ, Cooke-Bailey JN, Reitz C, Jun G, Naj A, Beecham GW, Liu Z, Carney RM, Vance JM, Cuccaro ML, Rajbhandary R, Vardarajan BNarayan, Wang L-S, Valladares O, Lin C-F, Larson EB, Graff-Radford NR, Evans D, De Jager PL, Crane PK, Buxbaum JD, Murrell JR, Raj T, Ertekin-Taner N, Logue MW, Baldwin CT, Green RC, Barnes LL, Cantwell LB, M Fallin D, Go RCP, Griffith P, Obisesan TO, Manly JJ, Lunetta KL, M Kamboh I, Lopez OL, Bennett DA, Hardy J, Hendrie HC, Hall KS, Goate AM, Lang R, Byrd GS, Kukull WA, Foroud TM, Farrer LA, Martin ER, Pericak-Vance MA, Schellenberg GD, Mayeux R, Haines JL, Thornton-Wells TA |
Corporate Authors | Alzheimer Disease Genetics Consortium |
Journal | Alzheimers Dement |
Volume | 12 |
Issue | 3 |
Pagination | 233-43 |
Date Published | 2016 Mar |
ISSN | 1552-5279 |
Keywords | African Americans, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, ATP-Binding Cassette Transporters, Chi-Square Distribution, Chromosome Aberrations, Cohort Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Sialic Acid Binding Ig-like Lectin 3 |
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. |
DOI | 10.1016/j.jalz.2015.02.012 |
Alternate Journal | Alzheimers Dement |
PubMed ID | 26092349 |
PubMed Central ID | PMC4681680 |
Grant List | P30AG012300 / AG / NIA 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 R01AG025259 / AG / NIA NIH HHS / United States U01HG006375 / HG / NHGRI NIH HHS / United States P01AG002219 / AG / NIA NIH HHS / United States RF1 AG015819 / AG / NIA NIH HHS / United States R01AG026916 / AG / NIA NIH HHS / United States P50AG016582 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States R01 AG031581 / AG / NIA NIH HHS / United States P30AG10133 / AG / NIA NIH HHS / United States P50AG005138 / AG / NIA NIH HHS / United States P50AG016573 / AG / NIA NIH HHS / United States U01HG004610 / HG / NHGRI NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States P50AG023501 / AG / NIA NIH HHS / United States R01 AG030146 / AG / NIA NIH HHS / United States U01AG016976 / AG / NIA NIH HHS / United States T32 MH065215 / MH / NIMH NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States R01AG031581 / AG / NIA NIH HHS / United States R01CA129769 / CA / NCI NIH HHS / United States R01AG027944 / AG / NIA NIH HHS / United States KL2RR024151 / RR / NCRR NIH HHS / United States P01 AG003991 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States P01 AG026276 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R01AG009956 / AG / NIA NIH HHS / United States R01MH080295 / MH / NIMH NIH HHS / United States R01AG17917 / AG / NIA NIH HHS / United States R01AG020688 / AG / NIA NIH HHS / United States R01AG222018 / AG / NIA NIH HHS / United States RC2AG036650 / AG / NIA NIH HHS / United States P30AG010124 / AG / NIA NIH HHS / United States P50AG008702 / AG / NIA NIH HHS / United States R37AG015473 / AG / NIA NIH HHS / United States P01AG03991 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States UL1 TR001108 / TR / NCATS NIH HHS / United States U24AG021886 / AG / NIA NIH HHS / United States P50AG008671 / AG / NIA NIH HHS / United States P50AG016574 / AG / NIA NIH HHS / United States R01AG032990 / AG / NIA NIH HHS / United States R01AG028786 / AG / NIA NIH HHS / United States P50AG016576 / AG / NIA NIH HHS / United States RC2AG036528 / AG / NIA NIH HHS / United States P50AG005146 / AG / NIA NIH HHS / United States UL1RR029893 / RR / NCRR NIH HHS / United States K23AG034550 / AG / NIA NIH HHS / United States R01AG33193 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States P01AG010491 / AG / NIA NIH HHS / United States U24AG02188 / AG / NIA NIH HHS / United States R01AG037212 / AG / NIA NIH HHS / United States P50AG05128 / AG / NIA NIH HHS / United States R01AG30146 / AG / NIA NIH HHS / United States R01AG1101 / AG / NIA NIH HHS / United States T32 MH65215 / MH / NIMH NIH HHS / United States R01AG030653 / AG / NIA NIH HHS / United States P30AG008017 / AG / NIA NIH HHS / United States R01AG019757 / AG / NIA NIH HHS / United States P50AG016575 / AG / NIA NIH HHS / United States R01 CA129769 / CA / NCI NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States P50MH60451 / MH / NIMH NIH HHS / United States P50AG005136 / AG / NIA NIH HHS / United States R01AG15819 / AG / NIA NIH HHS / United States U01AG032984 / AG / NIA NIH HHS / United States R01AG017173 / AG / NIA NIH HHS / United States P50NS39764 / NS / NINDS NIH HHS / United States U01AG06781 / AG / NIA NIH HHS / United States K12 HD043483 / HD / NICHD NIH HHS / United States L30 AG048601 / AG / NIA NIH HHS / United States P50AG016577 / AG / NIA NIH HHS / United States P30AG08051 / AG / NIA NIH HHS / United States P50AG005681 / AG / NIA NIH HHS / United States P30AG13846 / AG / NIA NIH HHS / United States P30AG10161 / AG / NIA NIH HHS / United States P30AG013854 / AG / NIA NIH HHS / United States P50AG005131 / AG / NIA NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States P30 AG019610 / AG / NIA NIH HHS / United States P50AG005142 / AG / NIA NIH HHS / United States P20MD000546 / MD / NIMHD NIH HHS / United States P30AG019610 / AG / NIA NIH HHS / United States 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 P50AG025688 / AG / NIA NIH HHS / United States MO1RR00096 / RR / NCRR NIH HHS / United States U24AG026390 / AG / NIA NIH HHS / United States P30AG028377 / AG / NIA NIH HHS / United States T32 EY21453-2 / EY / NEI NIH HHS / United States UL1RR02777 / RR / NCRR NIH HHS / United States P01AG019724 / AG / NIA NIH HHS / United States R01AG041718 / AG / NIA NIH HHS / United States |