Two novel loci,COBL and SLC10A2, for Alzheimer's disease in African Americans |
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| Authors: | Jesse Mez Jaeyoon Chung Gyungah Jun Joshua Kriegel Alexandra P. Bourlas Richard Sherva Mark W. Logue Lisa L. Barnes David A. Bennett Joseph D. Buxbaum Goldie S. Byrd Paul K. Crane Nilüfer Ertekin-Taner Denis Evans M. Daniele Fallin Tatiana Foroud Alison Goate Neill R. Graff-Radford Lindsay A. Farrer |
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| Affiliation: | 1. Department of Neurology, Boston University School of Medicine, Boston, MA, USA;2. Alzheimer''s Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA;3. Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA;4. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA;5. Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA;6. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA;7. Rush Alzheimer''s Disease Center, Rush University Medical Center, Chicago, IL, USA;8. Departments of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA;9. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA;10. Department of Biology, North Carolina A & T State University, Greensboro, NC, USA;11. Department of Medicine, University of Washington, Seattle, WA, USA;12. Department of Neurology, Mayo Clinic, Jacksonville, FL, USA;13. Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD, USA;14. Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, MD, USA;15. Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA;p. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA;q. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA;r. Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA;s. Department of Epidemiology, University of Washington, Seattle, WA, USA;t. Group Health, Group Health Research Institute, Seattle, WA, USA;u. Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA;v. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA;w. The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA;x. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA;y. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA |
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| Abstract: | ![]()
IntroductionAfrican Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.MethodsWe conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs.ResultsTwo SNPs at novel loci, rs112404845 (P = 3.8 × 10?8), upstream of COBL, and rs16961023 (P = 4.6 × 10?8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability.DiscussionAn informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS. |
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| Keywords: | Alzheimer's disease Genome-wide association study (GWAS) African Americans Informed conditioning on clinical covariates Age Sex differences Diabetes Smoking Education Resveratrol |
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