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

Publication ,  Journal Article
Bonham, LW; Evans, DS; Liu, Y; Cummings, SR; Yaffe, K; Yokoyama, JS
Published in: Am J Alzheimers Dis Other Demen
May 2018

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.

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Published In

Am J Alzheimers Dis Other Demen

DOI

EISSN

1938-2731

Publication Date

May 2018

Volume

33

Issue

3

Start / End Page

153 / 165

Location

United States

Related Subject Headings

  • Neurotransmitter Agents
  • Male
  • KCNQ2 Potassium Channel
  • Humans
  • Hippocampus
  • Geriatrics
  • Genetic Association Studies
  • GTP-Binding Protein gamma Subunits
  • Female
  • Cognitive Dysfunction
 

Citation

APA
Chicago
ICMJE
MLA
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Bonham, L. W., Evans, D. S., Liu, Y., Cummings, S. R., Yaffe, K., & Yokoyama, J. S. (2018). Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for GNG4 and KCNQ2 Genes. Am J Alzheimers Dis Other Demen, 33(3), 153–165. https://doi.org/10.1177/1533317517739384
Bonham, Luke W., Daniel S. Evans, Yongmei Liu, Steven R. Cummings, Kristine Yaffe, and Jennifer S. Yokoyama. “Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for GNG4 and KCNQ2 Genes.Am J Alzheimers Dis Other Demen 33, no. 3 (May 2018): 153–65. https://doi.org/10.1177/1533317517739384.
Bonham LW, Evans DS, Liu Y, Cummings SR, Yaffe K, Yokoyama JS. Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for GNG4 and KCNQ2 Genes. Am J Alzheimers Dis Other Demen. 2018 May;33(3):153–65.
Bonham, Luke W., et al. “Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for GNG4 and KCNQ2 Genes.Am J Alzheimers Dis Other Demen, vol. 33, no. 3, May 2018, pp. 153–65. Pubmed, doi:10.1177/1533317517739384.
Bonham LW, Evans DS, Liu Y, Cummings SR, Yaffe K, Yokoyama JS. Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for GNG4 and KCNQ2 Genes. Am J Alzheimers Dis Other Demen. 2018 May;33(3):153–165.
Journal cover image

Published In

Am J Alzheimers Dis Other Demen

DOI

EISSN

1938-2731

Publication Date

May 2018

Volume

33

Issue

3

Start / End Page

153 / 165

Location

United States

Related Subject Headings

  • Neurotransmitter Agents
  • Male
  • KCNQ2 Potassium Channel
  • Humans
  • Hippocampus
  • Geriatrics
  • Genetic Association Studies
  • GTP-Binding Protein gamma Subunits
  • Female
  • Cognitive Dysfunction