Horgusluoglu-Moloch, EmrinRisacher, Shannon L.Crane, Paul K.Hibar, DerrekThompson, Paul M.Saykin, Andrew J.Nho, KwangsikAlzheimer’s Disease Neuroimaging Initiative (ADNI)2020-01-172020-01-172019-10-10Horgusluoglu-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. Scientific reports, 9(1), 14498. doi:10.1038/s41598-019-50507-3https://hdl.handle.net/1805/21872Adult 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.en-USAttribution 4.0 InternationalGenome-wide association studiesAdult neurogenesisArticle