. 2017 Feb;13(2):119-129.

doi: 10.1016/j.jalz.2016.09.002. Epub 2016 Oct 20.

Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans

Jesse Mez¹, Jaeyoon Chung², Gyungah Jun³, Joshua Kriegel⁴, Alexandra P Bourlas⁴, Richard Sherva², Mark W Logue⁵, Lisa L Barnes⁶, David A Bennett⁷, Joseph D Buxbaum⁸, Goldie S Byrd⁹, Paul K Crane¹⁰, Nilüfer Ertekin-Taner¹¹, Denis Evans⁶, M Daniele Fallin¹², Tatiana Foroud¹³, Alison Goate⁸, Neill R Graff-Radford¹¹, Kathleen S Hall¹⁴, M Ilyas Kamboh¹⁵, Walter A Kukull¹⁶, Eric B Larson¹⁷, Jennifer J Manly¹⁸; Alzheimer's Disease Genetics Consortium; Jonathan L Haines¹⁹, Richard Mayeux¹⁸, Margaret A Pericak-Vance²⁰, Gerard D Schellenberg²¹, Kathryn L Lunetta²², Lindsay A Farrer²³

Affiliations

¹ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA. Electronic address: jessemez@bu.edu.
² Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
³ 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 Ophthalmology, Boston University School of Medicine, Boston, MA, USA.
⁴ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.
⁵ 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.
⁶ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
⁷ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; 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; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
⁹ Department of Biology, North Carolina A & T State University, Greensboro, NC, USA.
¹⁰ Department of Medicine, University of Washington, Seattle, WA, USA.
¹¹ Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹² Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD, USA; Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA.
¹³ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁴ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁵ Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁶ Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁷ Group Health, Group Health Research Institute, Seattle, WA, USA.
¹⁸ Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA.
¹⁹ Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
²⁰ The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
²¹ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²² Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
²³ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, 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 Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.

PMID: 27770636
PMCID: PMC5318231
DOI: 10.1016/j.jalz.2016.09.002

Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans

Jesse Mez et al. Alzheimers Dement. 2017 Feb.

. 2017 Feb;13(2):119-129.

doi: 10.1016/j.jalz.2016.09.002. Epub 2016 Oct 20.

Authors

Affiliations

¹ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA. Electronic address: jessemez@bu.edu.
² Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
³ 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 Ophthalmology, Boston University School of Medicine, Boston, MA, USA.
⁴ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.
⁵ 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.
⁶ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
⁷ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; 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; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
⁹ Department of Biology, North Carolina A & T State University, Greensboro, NC, USA.
¹⁰ Department of Medicine, University of Washington, Seattle, WA, USA.
¹¹ Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹² Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD, USA; Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA.
¹³ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁴ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁵ Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁶ Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁷ Group Health, Group Health Research Institute, Seattle, WA, USA.
¹⁸ Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA.
¹⁹ Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
²⁰ The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
²¹ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²² Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
²³ Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, 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 Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.

PMID: 27770636
PMCID: PMC5318231
DOI: 10.1016/j.jalz.2016.09.002

Abstract

Introduction: African 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.

Methods: We 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.

Results: Two 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.

Discussion: An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.

Keywords: ABCA7; APOE; African Americans; Age; Alzheimer's disease; COBL; Diabetes; Education; Genome-wide association study (GWAS); Informed conditioning on clinical covariates; Resveratrol; SLC10A2; Sex differences; Smoking.

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Figures

**Fig. 1**
(A) Regional association plot of the *COBL* region on chromosome 7 and (B) forest plots for rs112404845, the top single-nucleotide polymorphism in the region. Abbreviations: ACT, Adult Changes in Thought; ADC, Alzheimer’s Disease Center; ADGC, Alzheimer’s Disease Genetics Consortium; CHAP, Chicago Health and Aging Project; CI, confidence interval; *COBL*, Cordon-Bleu WH2 Repeat Protein; GenerAAtions, Genetic and Environmental Risk Factors for Alzheimer Disease among African Americans; and MAF, minor allele frequency.

**Fig. 2**
(A) Regional association plot of the *SLC10A2* region on chromosome 13 and (B) forest plots for rs16961023, the top single-nucleotide polymorphism in the region. Abbreviations: ACT, Adult Changes in Thought; ADC, Alzheimer’s Disease Center; ADGC, Alzheimer’s Disease Genetics Consortium; CHAP, Chicago Health and Aging Project; CI, confidence interval; GenerAAtions, Genetic and Environmental Risk Factors for Alzheimer Disease among African Americans; MAF, minor allele frequency; and *SLC10A2*, solute carrier family 10, member 2.

See this image and copyright information in PMC

References

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Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans

Affiliations

Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous