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

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.

SUBMITTER: Deters KD

PROVIDER: S-EPMC5583024 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Deters Kacie D KD Nho Kwangsik K Risacher Shannon L SL Kim Sungeun S Ramanan Vijay K VK Crane Paul K PK Apostolova Liana G LG Saykin Andrew J AJ

Brain and language 20170531

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 associat ...[more]

PMID: 28577822

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Project description:BackgroundThousands of research studies concerning genome-wide association studies (GWAS) in Alzheimer's disease (AD) have been published in the last decades. However, a comprehensive understanding of the current research status and future development trends of GWAS in AD have not been clearly shown. In this study, we tried to gain a systematic overview of GWAS in AD by bibliometric and visualization analysis.MethodsThe literature search terms are: ("genome-wide analysis" or "genome-wide association study" or "whole-genome analysis") AND ("Alzheimer's Disease" or "Alzheimer Disease"). Relevant publications were extracted from the Web of Science Core Collection (WoSCC) database. Collected data were further analyzed using VOSviewer, CiteSpace and R package Bibliometrix. The countries, institutions, authors and scholar collaborations were investigated. The co-citation analysis of publications was visualized. In addition, research hotspots and fronts were examined.ResultsA total of 1,350 publications with 59,818 citations were identified. The number of publications and citations presented a significant rising trend since 2013. The United States was the leading country with an overwhelming number of publications (775) and citations (42,237). The University of Washington and Harvard University were the most prolific institutions with 101 publications each. Bennett DA was the most influential researcher with the highest local H-index. Neurobiology of Aging was the journal with the highest number of publications. Aβ, tau, immunity, microglia and DNA methylation were research hotspots. Disease and causal variants were research fronts.ConclusionThe most frequently studied AD pathogenesis and research hotspots are (1) Aβ and tau, (2) immunity and microglia, with TREM2 as a potential immunotherapy target, and (3) DNA methylation. The research fronts are (1) looking for genetic similarities between AD and other neurological diseases and syndromes, and (2) searching for causal variants of AD. These hotspots suggest noteworthy directions for future studies on AD pathogenesis and genetics, in which basic research regarding immunity is promising for clinical conversion. The current under-researched directions are (1) GWAS in AD biomarkers based on large sample sizes, (2) studies of causal variants of AD, and (3) GWAS in AD based on non-European populations, which need to be strengthened in the future.

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

Publications

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

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