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

Timothy J. Hohman, Jessica N. Cooke-Bailey, Christiane Reitz, Gyungah Jun, Adam Naj, Gary W. Beecham, Zhi Liu, Regina M. Carney, Jeffrey M. Vance, Michael L. Cuccaro, Ruchita Rajbhandary, Badri Narayan Vardarajan, Li San Wang, Otto Valladares, Chiao Feng Lin, Eric B. Larson, Neill R. Graff-Radford, Denis Evans, Philip L. De Jager, Paul K. CraneJoseph D. Buxbaum, Jill R. Murrell, Towfique Raj, Nilufer Ertekin-Taner, Mark W. Logue, Clinton T. Baldwin, Robert C. Green, Lisa L. Barnes, Laura B. Cantwell, M. Daniele Fallin, Rodney C P Go, Patrick Griffith, Thomas O. Obisesan, Jennifer J. Manly, Kathryn L. Lunetta, M. Ilyas Kamboh, Oscar L. Lopez, David A. Bennett, John Hardy, Hugh Hendrie, Kathleen Hall, Alison M. Goate, Rosalyn Lang, Goldie S. Byrd, Walter A. Kukull, Tatiana Foroud, Lindsay A. Farrer, Eden R. Martin, Margaret A. Pericak-Vance, Gerard D. Schellenberg, Richard Mayeux, Jonathan L. Haines, Tricia A. Thornton-Wells

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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. We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. 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. Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.

Original languageEnglish
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - 2015

Fingerprint

African Americans
Alzheimer Disease
Genome-Wide Association Study

Keywords

  • Admixture mapping
  • African-American
  • Alzheimer's disease
  • Genome-wide association analysis (GWAS)
  • Local admixture
  • Local ancestry

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy

Cite this

Hohman, T. J., Cooke-Bailey, J. N., Reitz, C., Jun, G., Naj, A., Beecham, G. W., ... Thornton-Wells, T. A. (Accepted/In press). Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk. Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2015.02.012

Global and local ancestry in African-Americans : Implications for Alzheimer's disease risk. / Hohman, Timothy J.; Cooke-Bailey, Jessica N.; Reitz, Christiane; Jun, Gyungah; Naj, Adam; Beecham, Gary W.; Liu, Zhi; Carney, Regina M.; Vance, Jeffrey M.; Cuccaro, Michael L.; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li San; Valladares, Otto; Lin, Chiao Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark W.; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C P; Griffith, Patrick; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hardy, John; Hendrie, Hugh; Hall, Kathleen; Goate, Alison M.; Lang, Rosalyn; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana; Farrer, Lindsay A.; Martin, Eden R.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Mayeux, Richard; Haines, Jonathan L.; Thornton-Wells, Tricia A.

In: Alzheimer's and Dementia, 2015.

Research output: Contribution to journalArticle

Hohman, TJ, Cooke-Bailey, JN, Reitz, C, Jun, G, Naj, A, Beecham, GW, Liu, Z, Carney, RM, Vance, JM, Cuccaro, ML, Rajbhandary, R, Vardarajan, BN, Wang, LS, Valladares, O, Lin, CF, 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, Fallin, MD, Go, RCP, Griffith, P, Obisesan, TO, Manly, JJ, Lunetta, KL, Kamboh, MI, Lopez, OL, Bennett, DA, Hardy, J, Hendrie, H, Hall, K, Goate, AM, Lang, R, Byrd, GS, Kukull, WA, Foroud, T, Farrer, LA, Martin, ER, Pericak-Vance, MA, Schellenberg, GD, Mayeux, R, Haines, JL & Thornton-Wells, TA 2015, 'Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk', Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2015.02.012
Hohman, Timothy J. ; Cooke-Bailey, Jessica N. ; Reitz, Christiane ; Jun, Gyungah ; Naj, Adam ; Beecham, Gary W. ; Liu, Zhi ; Carney, Regina M. ; Vance, Jeffrey M. ; Cuccaro, Michael L. ; Rajbhandary, Ruchita ; Vardarajan, Badri Narayan ; Wang, Li San ; Valladares, Otto ; Lin, Chiao Feng ; Larson, Eric B. ; Graff-Radford, Neill R. ; Evans, Denis ; De Jager, Philip L. ; Crane, Paul K. ; Buxbaum, Joseph D. ; Murrell, Jill R. ; Raj, Towfique ; Ertekin-Taner, Nilufer ; Logue, Mark W. ; Baldwin, Clinton T. ; Green, Robert C. ; Barnes, Lisa L. ; Cantwell, Laura B. ; Fallin, M. Daniele ; Go, Rodney C P ; Griffith, Patrick ; Obisesan, Thomas O. ; Manly, Jennifer J. ; Lunetta, Kathryn L. ; Kamboh, M. Ilyas ; Lopez, Oscar L. ; Bennett, David A. ; Hardy, John ; Hendrie, Hugh ; Hall, Kathleen ; Goate, Alison M. ; Lang, Rosalyn ; Byrd, Goldie S. ; Kukull, Walter A. ; Foroud, Tatiana ; Farrer, Lindsay A. ; Martin, Eden R. ; Pericak-Vance, Margaret A. ; Schellenberg, Gerard D. ; Mayeux, Richard ; Haines, Jonathan L. ; Thornton-Wells, Tricia A. / Global and local ancestry in African-Americans : Implications for Alzheimer's disease risk. In: Alzheimer's and Dementia. 2015.
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title = "Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk",
abstract = "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. We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. 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. 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 = "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 Hugh Hendrie and Kathleen Hall and Goate, {Alison M.} and Rosalyn Lang and Byrd, {Goldie S.} and Kukull, {Walter A.} and Tatiana Foroud and Farrer, {Lindsay A.} and Martin, {Eden R.} and Pericak-Vance, {Margaret A.} and Schellenberg, {Gerard D.} and Richard Mayeux and Haines, {Jonathan L.} and Thornton-Wells, {Tricia A.}",
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TY - JOUR

T1 - Global and local ancestry in African-Americans

T2 - Implications for Alzheimer's disease risk

AU - Hohman, Timothy J.

AU - Cooke-Bailey, Jessica N.

AU - Reitz, Christiane

AU - Jun, Gyungah

AU - Naj, Adam

AU - Beecham, Gary W.

AU - Liu, Zhi

AU - Carney, Regina M.

AU - Vance, Jeffrey M.

AU - Cuccaro, Michael L.

AU - Rajbhandary, Ruchita

AU - Vardarajan, Badri Narayan

AU - Wang, Li San

AU - Valladares, Otto

AU - Lin, Chiao Feng

AU - Larson, Eric B.

AU - Graff-Radford, Neill R.

AU - Evans, Denis

AU - De Jager, Philip L.

AU - Crane, Paul K.

AU - Buxbaum, Joseph D.

AU - Murrell, Jill R.

AU - Raj, Towfique

AU - Ertekin-Taner, Nilufer

AU - Logue, Mark W.

AU - Baldwin, Clinton T.

AU - Green, Robert C.

AU - Barnes, Lisa L.

AU - Cantwell, Laura B.

AU - Fallin, M. Daniele

AU - Go, Rodney C P

AU - Griffith, Patrick

AU - Obisesan, Thomas O.

AU - Manly, Jennifer J.

AU - Lunetta, Kathryn L.

AU - Kamboh, M. Ilyas

AU - Lopez, Oscar L.

AU - Bennett, David A.

AU - Hardy, John

AU - Hendrie, Hugh

AU - Hall, Kathleen

AU - Goate, Alison M.

AU - Lang, Rosalyn

AU - Byrd, Goldie S.

AU - Kukull, Walter A.

AU - Foroud, Tatiana

AU - Farrer, Lindsay A.

AU - Martin, Eden R.

AU - Pericak-Vance, Margaret A.

AU - Schellenberg, Gerard D.

AU - Mayeux, Richard

AU - Haines, Jonathan L.

AU - Thornton-Wells, Tricia A.

PY - 2015

Y1 - 2015

N2 - 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. We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. 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. Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.

AB - 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. We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. 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. Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.

KW - Admixture mapping

KW - African-American

KW - Alzheimer's disease

KW - Genome-wide association analysis (GWAS)

KW - Local admixture

KW - Local ancestry

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U2 - 10.1016/j.jalz.2015.02.012

DO - 10.1016/j.jalz.2015.02.012

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JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

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