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

TitleTwo novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans.
Publication TypeJournal Article
Year of Publication2017
AuthorsMez, J, Chung, J, Jun, G, Kriegel, J, Bourlas, AP, Sherva, R, Logue, MW, Barnes, LL, Bennett, DA, Buxbaum, JD, Byrd, GS, Crane, PK, Ertekin-Taner, N, Evans, D, M Fallin, D, Foroud, T, Goate, A, Graff-Radford, NR, Hall, KS, M Kamboh, I, Kukull, WA, Larson, EB, Manly, JJ, Haines, JL, Mayeux, R, Pericak-Vance, MA, Schellenberg, GD, Lunetta, KL, Farrer, LA
Corporate AuthorsAlzheimer's Disease Genetics Consortium
JournalAlzheimers Dement
Volume13
Issue2
Pagination119-129
Date Published2017 02
ISSN1552-5279
KeywordsAfrican Americans, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, ATP-Binding Cassette Transporters, Diabetes Complications, Educational Status, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Microfilament Proteins, Organic Anion Transporters, Sodium-Dependent, Polymorphism, Single Nucleotide, Prevalence, Smoking, Symporters
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), upstream of COBL, and rs16961023 (P = 4.6 × 10), 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.

DOI10.1016/j.jalz.2016.09.002
Alternate JournalAlzheimers Dement
PubMed ID27770636
PubMed Central IDPMC5318231
Grant ListP30 AG010124 / AG / NIA NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
R01 AG009029 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
R01 AG009956 / AG / NIA NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
RC2 AG036650 / AG / NIA NIH HHS / United States
R01 AG019085 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
U01 HG008657 / HG / NHGRI NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
U01 AG016976 / AG / NIA 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
R01 AG026390 / AG / NIA NIH HHS / United States
R01 AG028786 / AG / NIA NIH HHS / United States
RF1 AG051504 / AG / NIA NIH HHS / United States
U24 AG041689 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG032990 / AG / NIA NIH HHS / United States
R37 AG015473 / AG / NIA NIH HHS / United States
U24 AG026395 / AG / NIA NIH HHS / United States
R01 NS080820 / NS / NINDS NIH HHS / United States
P50 AG005133 / AG / NIA NIH HHS / United States
U01 AG006781 / AG / NIA NIH HHS / United States
K23 AG046377 / AG / NIA NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
R01 AG048927 / AG / NIA NIH HHS / United States
R01 AG037212 / AG / NIA NIH HHS / United States
R01 AG020688 / AG / NIA NIH HHS / United States
R01 AG022018 / AG / NIA NIH HHS / United States
R01 AG030653 / AG / NIA NIH HHS / United States
P20 MD000546 / MD / NIMHD NIH HHS / United States
R01 AG027944 / AG / NIA NIH HHS / United States
R01 AG025259 / AG / NIA NIH HHS / United States
R01 AG041718 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States