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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Horgusluoglu-Moloch, E; Risacher, SL; Crane, PK; Hibar, D; Thompson, PM; Saykin, AJ; Nho, K; Alzheimer’s Disease Neuroimaging Initiative (ADNI),

Published Date

  • October 10, 2019

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 14498 -

PubMed ID

  • 31601890

Pubmed Central ID

  • 31601890

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-019-50507-3

Language

  • eng

Conference Location

  • England