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Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways.

Publication ,  Journal Article
Horgusluoglu-Moloch, E; Risacher, SL; Crane, PK; Hibar, D; Thompson, PM; Saykin, AJ; Nho, K; Alzheimer’s Disease Neuroimaging Initiative (ADNI),
Published in: Sci Rep
October 10, 2019

Adult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer's Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 10, 2019

Volume

9

Issue

1

Start / End Page

14498

Location

England

Related Subject Headings

  • Signal Transduction
  • Organ Size
  • Neurons
  • Neurogenesis
  • Methionine Sulfoxide Reductases
  • Male
  • Humans
  • Hippocampus
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

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Horgusluoglu-Moloch, E., Risacher, S. L., Crane, P. K., Hibar, D., Thompson, P. M., Saykin, A. J., … Alzheimer’s Disease Neuroimaging Initiative (ADNI), . (2019). Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways. Sci Rep, 9(1), 14498. https://doi.org/10.1038/s41598-019-50507-3
Horgusluoglu-Moloch, Emrin, Shannon L. Risacher, Paul K. Crane, Derrek Hibar, Paul M. Thompson, Andrew J. Saykin, Kwangsik Nho, and Kwangsik Alzheimer’s Disease Neuroimaging Initiative (ADNI). “Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways.Sci Rep 9, no. 1 (October 10, 2019): 14498. https://doi.org/10.1038/s41598-019-50507-3.
Horgusluoglu-Moloch E, Risacher SL, Crane PK, Hibar D, Thompson PM, Saykin AJ, et al. Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways. Sci Rep. 2019 Oct 10;9(1):14498.
Horgusluoglu-Moloch, Emrin, et al. “Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways.Sci Rep, vol. 9, no. 1, Oct. 2019, p. 14498. Pubmed, doi:10.1038/s41598-019-50507-3.
Horgusluoglu-Moloch E, Risacher SL, Crane PK, Hibar D, Thompson PM, Saykin AJ, Nho K, Alzheimer’s Disease Neuroimaging Initiative (ADNI). Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways. Sci Rep. 2019 Oct 10;9(1):14498.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 10, 2019

Volume

9

Issue

1

Start / End Page

14498

Location

England

Related Subject Headings

  • Signal Transduction
  • Organ Size
  • Neurons
  • Neurogenesis
  • Methionine Sulfoxide Reductases
  • Male
  • Humans
  • Hippocampus
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease