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

Alzheimer's Disease Genetics Consortium

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalAlzheimer's and Dementia
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

African Americans
Genome-Wide Association Study
Alzheimer Disease
Single Nucleotide Polymorphism
Genome
Educational Status
Smoking
Conditioning (Psychology)

Keywords

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

ASJC Scopus subject areas

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

Cite this

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

In: Alzheimer's and Dementia, Vol. 13, No. 2, 01.02.2017, p. 119-129.

Research output: Contribution to journalArticle

Alzheimer's Disease Genetics Consortium. / Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans. In: Alzheimer's and Dementia. 2017 ; Vol. 13, No. 2. pp. 119-129.
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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.",
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T1 - Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans

AU - Alzheimer's Disease Genetics Consortium

AU - Mez, Jesse

AU - Chung, Jaeyoon

AU - Jun, Gyungah

AU - Kriegel, Joshua

AU - Bourlas, Alexandra P.

AU - Sherva, Richard

AU - Logue, Mark W.

AU - Barnes, Lisa L.

AU - Bennett, David A.

AU - Buxbaum, Joseph D.

AU - Byrd, Goldie S.

AU - Crane, Paul K.

AU - Ertekin-Taner, Nilüfer

AU - Evans, Denis

AU - Fallin, M. Daniele

AU - Foroud, Tatiana

AU - Goate, Alison

AU - Graff-Radford, Neill R.

AU - Hall, Kathleen S.

AU - Kamboh, M. Ilyas

AU - Kukull, Walter A.

AU - Larson, Eric B.

AU - Manly, Jennifer J.

AU - Haines, Jonathan L.

AU - Mayeux, Richard

AU - Pericak-Vance, Margaret A

AU - Schellenberg, Gerard D.

AU - Lunetta, Kathryn L.

AU - Farrer, Lindsay A.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

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KW - Informed conditioning on clinical covariates

KW - Resveratrol

KW - Sex differences

KW - SLC10A2

KW - Smoking

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