Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for GNG4 and KCNQ2 Genes.


Journal Article

BACKGROUND/RATIONALE: Experimental studies support the role of neurotransmitter genes in dementia risk, but human studies utilizing single variants in candidate genes have had limited success. METHODS: We used the gene-based testing program Versatile Gene-based Association Study to assess whether aggregate variation across 6 neurotransmitter pathways influences risk of cognitive decline in 8159 cognitively normal elderly (≥65 years old) adults from 3 community-based cohorts. RESULTS: Common genetic variation in GNG4 and KCNQ2 was associated with cognitive decline. In human brain tissue data sets, both GNG4 and KCNQ2 show higher expression in hippocampus relative to other brain regions; GNG4 expression decreases with advancing age. Both GNG4 and KCNQ2 show highest expression in fetal astrocytes. CONCLUSION: Genetic variation analyses and gene expression data suggest that GNG4 and KCNQ2 may be associated with cognitive decline in normal aging. Gene-based testing of neurotransmitter pathways may confirm and reveal novel risk genes in future studies of healthy cognitive aging.

Full Text

Duke Authors

Cited Authors

  • Bonham, LW; Evans, DS; Liu, Y; Cummings, SR; Yaffe, K; Yokoyama, JS

Published Date

  • May 2018

Published In

Volume / Issue

  • 33 / 3

Start / End Page

  • 153 - 165

PubMed ID

  • 29338302

Pubmed Central ID

  • 29338302

Electronic International Standard Serial Number (EISSN)

  • 1938-2731

Digital Object Identifier (DOI)

  • 10.1177/1533317517739384


  • eng

Conference Location

  • United States