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

Alzheimer's Disease Genetics Consortium

Research output: Contribution to journalArticle

22 Scopus citations

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

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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

ASJC Scopus subject areas

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

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