Genome-wide association study of language performance in Alzheimer's disease

Kacie D. Deters, Kwangsik Nho, Shannon L. Risacher, Sungeun Kim, Vijay K. Ramanan, Paul K. Crane, Liana G. Apostolova, Andrew Saykin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Language impairment is common in prodromal stages of Alzheimer's disease (AD) and progresses over time. However, the genetic architecture underlying language performance is poorly understood. To identify novel genetic variants associated with language performance, we analyzed brain MRI and performed a genome-wide association study (GWAS) using a composite measure of language performance from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=1560). The language composite score was associated with brain atrophy on MRI in language and semantic areas. GWAS identified GLI3 (GLI family zinc finger 3) as significantly associated with language performance (p<5×10-8). Enrichment of GWAS association was identified in pathways related to nervous system development and glutamate receptor function and trafficking. Our results, which warrant further investigation in independent and larger cohorts, implicate GLI3, a developmental transcription factor involved in patterning brain structures, as a putative gene associated with language dysfunction in AD.

Original languageEnglish (US)
JournalBrain and Language
DOIs
StateAccepted/In press - Aug 6 2015

Fingerprint

Genome-Wide Association Study
dementia
Alzheimer Disease
Language
language
performance
brain
Brain
Prodromal Symptoms
Genome
Alzheimer's Disease
Zinc Fingers
Glutamate Receptors
system development
Semantics
Neuroimaging
Nervous System
Atrophy
Transcription Factors
semantics

Keywords

  • Alzheimer's disease
  • GLI3
  • GWAS
  • Language performance
  • Neuroimaging

ASJC Scopus subject areas

  • Language and Linguistics
  • Experimental and Cognitive Psychology
  • Linguistics and Language
  • Cognitive Neuroscience
  • Speech and Hearing

Cite this

Genome-wide association study of language performance in Alzheimer's disease. / Deters, Kacie D.; Nho, Kwangsik; Risacher, Shannon L.; Kim, Sungeun; Ramanan, Vijay K.; Crane, Paul K.; Apostolova, Liana G.; Saykin, Andrew.

In: Brain and Language, 06.08.2015.

Research output: Contribution to journalArticle

Deters, Kacie D. ; Nho, Kwangsik ; Risacher, Shannon L. ; Kim, Sungeun ; Ramanan, Vijay K. ; Crane, Paul K. ; Apostolova, Liana G. ; Saykin, Andrew. / Genome-wide association study of language performance in Alzheimer's disease. In: Brain and Language. 2015.
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