. 2016 Mar;12(3):233-43.

doi: 10.1016/j.jalz.2015.02.012. Epub 2015 Jun 16.

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

Timothy J Hohman¹, Jessica N Cooke-Bailey¹, Christiane Reitz², Gyungah Jun³, Adam Naj⁴, Gary W Beecham⁵, Zhi Liu⁵, Regina M Carney⁶, Jeffrey M Vance⁷, Michael L Cuccaro⁸, Ruchita Rajbhandary⁵, Badri Narayan Vardarajan², Li-San Wang⁹, Otto Valladares⁹, Chiao-Feng Lin⁹, Eric B Larson¹⁰, Neill R Graff-Radford¹¹, Denis Evans¹², Philip L De Jager¹³, Paul K Crane¹⁰, Joseph D Buxbaum¹⁴, Jill R Murrell¹⁵, Towfique Raj¹³, Nilufer Ertekin-Taner¹¹, Mark W Logue¹⁶, Clinton T Baldwin¹⁷, Robert C Green¹⁸, Lisa L Barnes¹⁹, Laura B Cantwell⁹, M Daniele Fallin²⁰, Rodney C P Go²¹, Patrick Griffith²², Thomas O Obisesan²³, Jennifer J Manly², Kathryn L Lunetta²⁴, M Ilyas Kamboh²⁵, Oscar L Lopez²⁵, David A Bennett²⁶, John Hardy²⁷, Hugh C Hendrie²⁸, Kathleen S Hall²⁸, Alison M Goate²⁹, Rosalyn Lang³⁰, Goldie S Byrd³⁰, Walter A Kukull³¹, Tatiana M Foroud³², Lindsay A Farrer³³, Eden R Martin³⁴, Margaret A Pericak-Vance⁷, Gerard D Schellenberg⁹, Richard Mayeux², Jonathan L Haines¹, Tricia A Thornton-Wells³⁵; Alzheimer Disease Genetics Consortium

Affiliations

¹ Center for Human Genetics and Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
² Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
³ Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴ Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
⁶ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Psychiatry & Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
⁷ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
⁸ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Psychology, College of Arts & Sciences, University of Miami, Miami, FL, USA.
⁹ Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁰ Department of Medicine, University of Washington, Seattle, WA, USA; Group Health Research Institute, Group Health, Seattle, WA, USA.
¹¹ Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹² Department of Internal Medicine, Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA.
¹³ Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham & Women's Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute, Cambridge, MA, USA.
¹⁴ Department of Psychiatry, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA; Department of Genetics and Genomic Sciences, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA; Department of Neuroscience, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁶ Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
¹⁷ Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Pediatrics, Boston University School of Medicine, Boston, MA, USA.
¹⁸ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Partners Center for Personalized Genetic Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁹ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
²⁰ Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
²¹ School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
²² Division of Neurology, Department of Medicine, Morehouse School of Medicine, Atlanta, GA, USA.
²³ Division of Geriatrics, Howard University Hospital, Washington, DC, USA.
²⁴ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
²⁵ Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA; Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
²⁶ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
²⁷ Department of Molecular Neuroscience, Institute of Neurology, University College of London, London, UK.
²⁸ Indiana University Center for Aging Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁹ Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA; Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, USA.
³⁰ Department of Biology, North Carolina A & T State University, Greensboro, NC, USA.
³¹ National Alzheimer's Coordinating Center and Department of Epidemiology, University of Washington, Seattle, WA, USA.
³² Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
³³ Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA; Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA.
³⁴ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
³⁵ Center for Human Genetics and Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: t.thornton-wells@vanderbilt.edu.

PMID: 26092349
PMCID: PMC4681680
DOI: 10.1016/j.jalz.2015.02.012

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

Timothy J Hohman et al. Alzheimers Dement. 2016 Mar.

. 2016 Mar;12(3):233-43.

doi: 10.1016/j.jalz.2015.02.012. Epub 2015 Jun 16.

Authors

Affiliations

¹ Center for Human Genetics and Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
² Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
³ Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴ Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
⁶ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Psychiatry & Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
⁷ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
⁸ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Psychology, College of Arts & Sciences, University of Miami, Miami, FL, USA.
⁹ Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁰ Department of Medicine, University of Washington, Seattle, WA, USA; Group Health Research Institute, Group Health, Seattle, WA, USA.
¹¹ Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹² Department of Internal Medicine, Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA.
¹³ Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham & Women's Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute, Cambridge, MA, USA.
¹⁴ Department of Psychiatry, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA; Department of Genetics and Genomic Sciences, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA; Department of Neuroscience, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁶ Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
¹⁷ Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Pediatrics, Boston University School of Medicine, Boston, MA, USA.
¹⁸ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Partners Center for Personalized Genetic Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁹ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
²⁰ Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
²¹ School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
²² Division of Neurology, Department of Medicine, Morehouse School of Medicine, Atlanta, GA, USA.
²³ Division of Geriatrics, Howard University Hospital, Washington, DC, USA.
²⁴ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
²⁵ Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA; Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
²⁶ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
²⁷ Department of Molecular Neuroscience, Institute of Neurology, University College of London, London, UK.
²⁸ Indiana University Center for Aging Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁹ Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA; Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, USA.
³⁰ Department of Biology, North Carolina A & T State University, Greensboro, NC, USA.
³¹ National Alzheimer's Coordinating Center and Department of Epidemiology, University of Washington, Seattle, WA, USA.
³² Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
³³ Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; Department of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA; Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA.
³⁴ Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
³⁵ Center for Human Genetics and Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: t.thornton-wells@vanderbilt.edu.

PMID: 26092349
PMCID: PMC4681680
DOI: 10.1016/j.jalz.2015.02.012

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.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest.

Figures

**Figure 1. Differences in global ancestry between Alzheimer’s cases and controls**
Error bars represent the standard error of the mean. Group difference is statistically significant at p = 0.008.

**Figure 2. Differences in Local Ancestry by Chromosome: (a) Chr. 1, (b) Chr. 2, (c) Chr. 4, (d) Chr. 12 and (e) Chr. 19**
For each sub-figure, the top panel illustrates the proportion of African ancestry in cases (red) and controls (blue) across chromosome 1. The bottom panel presents the –log 10 p-value for a Wilcoxon rank sum test performed at each locus. The red dotted line signifies the threshold for statistical significance (FDR < 0.05).

See this image and copyright information in PMC

References

1. 2013 Alzheimer's disease facts and figures. Alzheimer's & Dementia. 9:208–245. - PubMed
1. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261:921–923. - PubMed
1. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nature genetics. 2009;41:1088–1093. - PMC - PubMed
1. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, et al. Common variants at ABCA7 , MS4A6A / MS4A4E , EPHA1 , CD33 and CD2AP are associated with Alzheimer's disease. Nature genetics. 2011;43:429–435. - PMC - PubMed
1. Jean-Charles L, Carla AI-V, Denis H, Adam CN, Rebecca S, Celine B, et al. Extended meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature genetics. 2013;45:1452–1458. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous