Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages

The Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Introduction: Genetic associations for endophenotypes of Alzheimer's disease (AD) in cognitive stages preceding AD have not been thoroughly evaluated. Methods: We conducted genome-wide association studies for AD-related endophenotypes including hippocampal volume, logical memory scores, and cerebrospinal fluid Aβ 42 and total/phosphorylated tau in cognitively normal (CN), mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative study. Results: In CN subjects, study-wide significant (P < 8.3 × 10 −9 ) loci were identified for total tau near SRRM4 and C14orf79 and for hippocampal volume near MTUS1. In mild cognitive impairment subjects, study-wide significant association was found with single nucleotide polymorphisms (SNPs) near ZNF804B for logical memory test of delayed recall scores. We found consistent expression patterns of C14orf40 and MTUS1 in carriers with risk alleles of expression SNPs and in brains of AD patients, compared with in the noncarriers and in brains of controls. Discussion: Our findings for AD-related brain changes before AD provide insight about early AD-related biological processes.

Original languageEnglish
Pages (from-to)623-633
Number of pages11
JournalAlzheimer's and Dementia
Issue number5
Publication statusPublished - 2018 May


  • ADNI
  • Alzheimer's disease
  • Biomarker
  • Cerebrospinal fluid
  • Coexpression network
  • Endophenotypes
  • Genome-wide association
  • Logical memory
  • MRI
  • Tau

ASJC Scopus subject areas

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


Dive into the research topics of 'Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages'. Together they form a unique fingerprint.

Cite this