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

Alzheimer’S Disease Neuroimaging Initiative (Adni)

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number14498
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Genome-Wide Association Study
Neurogenesis
Genes
Parahippocampal Gyrus
Dentate Gyrus
Neuroimaging
Meta-Analysis
Hippocampus
Alzheimer Disease
Phenotype
Gene Expression
Neurons

ASJC Scopus subject areas

  • General

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Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways. / Alzheimer’S Disease Neuroimaging Initiative (Adni).

In: Scientific reports, Vol. 9, No. 1, 14498, 01.12.2019.

Research output: Contribution to journalArticle

Alzheimer’S Disease Neuroimaging Initiative (Adni). / Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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abstract = "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.",
author = "{Alzheimer’S Disease Neuroimaging Initiative (Adni)} and Emrin Horgusluoglu-Moloch and Risacher, {Shannon L.} and Crane, {Paul K.} and Derrek Hibar and Thompson, {Paul M.} and Saykin, {Andrew J.} and Kwangsik Nho and Weiner, {Michael W.} and Paul Aisen and Ronald Petersen and Jack, {Clifford R.} and William Jagust and Trojanowki, {John Q.} and Toga, {Arthur W.} and Laurel Beckett and Green, {Robert C.} and John Morris and Shaw, {Leslie M.} and Jeffrey Kaye and Joseph Quinn and Lisa Silbert and Betty Lind and Raina Carter and Sara Dolen and Schneider, {Lon S.} and Sonia Pawluczyk and Mauricio Beccera and Liberty Teodoro and Spann, {Bryan M.} and James Brewer and Helen Vanderswag and Adam Fleisher and Heidebrink, {Judith L.} and Lord, {Joanne L.} and Mason, {Sara S.} and Albers, {Colleen S.} and David Knopman and Kris Johnson and Doody, {Rachelle S.} and Javier Villanueva-Meyer and Munir Chowdhury and Susan Rountree and Mimi Dang and Yaakov Stern and Honig, {Lawrence S.} and Bell, {Karen L.} and Beau Ances and Morris, {John C.} and Maria Carroll and Kyle Womack",
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