Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways
Year: 2019
Type: article
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.
Source: Scientific Reports
Authors: Emrin Horgusluoglu-Moloch, Shannon L. Risacher, Paul K. Crane, Derrek Hibar, Paul M. Thompson, Andrew J. Saykin, Kwangsik Nho, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, John C. Morris, Maria Carroll, Mary L. Creech, Erin Franklin, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, Randall Griffith, David Clark, David Geldmacher, John Brockington, Erik Roberson, Marissa Natelson Love, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Daniel Varon, Maria T. Greig, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Daniel D’Agostino, Stephanie Kielb, James E. Galvin, Brittany Cerbone, Christina A. Michel, Dana M. Pogorelec, Henry Rusinek, Mony J de Leon, Lidia Glodzik, Susan De Santi, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H. S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Tracy Kendall, Heather Johnson, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Cynthia Hunt, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, MarekMarsel Mesulam, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Anna Burke, Nadira Trncic, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Anahita Adeli, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Leslie Gordineer, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Norman Relkin, Gloria Chaing, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher
Institutions: Indiana University Indianapolis, Indiana University School of Medicine, Icahn School of Medicine at Mount Sinai, University of Washington, University of Southern California, Indiana University – Purdue University Indianapolis, University of California, San Francisco, University of California San Diego, Mayo Clinic, University of California, Berkeley, University of Pennsylvania, University of California, Davis, Brigham and Women's Hospital, Harvard University, Washington University in St. Louis, Oregon Health & Science University, University of Michigan, Banner Alzheimer’s Institute, Baylor College of Medicine, Georgetown University Medical Center, Columbia University Irving Medical Center, University of Alabama at Birmingham, Rush University Medical Center, Johns Hopkins University, New York University, Duke Medical Center, University of Kentucky, University of Rochester Medicine, University of California, Irvine, The University of Texas Southwestern Medical Center, Emory University, University of Kansas Medical Center, Indiana University, University of California, Los Angeles, Mayo Clinic in Florida, Yale University, Jewish General Hospital, McGill University, Sunnybrook Health Science Centre, Cleveland Clinic, Lou Ruvo Brain Institute, Northwestern University, Palm Beach Neurology, Premiere Research Institute, Stanford University, Banner Sun Health Research Institute, Boston University, Howard University, Case Western Reserve University, Dent Neurologic Institute, The Ohio State University, Albany Medical College, Hartford Hospital, Dartmouth–Hitchcock Medical Center, Wake Forest University Health Sciences, Rhode Island Hospital, Butler Hospital, Medical University of South Carolina, Nathan Kline Institute for Psychiatric Research, Cornell University, University of South Florida, USF Health Byrd Alzheimer's Institute
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,790
Funders: National Science Foundation, U.S. Department of Defense, Foundation for the National Institutes of Health, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, H. Lundbeck A/S, IXICO, National Institutes of Health, Genentech, School of Medicine, Indiana University, Canadian Institutes of Health Research, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, U.S. National Library of Medicine, National Center for Advancing Translational Sciences
Awards: G1012222616, G104586243, G1133087115, G1298807586, G1308337445, Indiana Alzheimer Disease Center, Bioinformatics Strategies for Multidimensional Brain Imaging Genetics, G1552963388, G1554142629, G1593117279, G1650819308, G1654311910, G1823308732, G1880935189, G1886977002, III: Small: Collaborative Research: A Large-Scale Data Mining Framework for Genome-Wide Mapping of Multi-Modal Phenotypic Biomarkers and Outcome Prediction, Alzheimer's Disease Neuroimaging Initiative, G2100670906, G2105457377, G2152643862, G2189010064, G2314325775, G2340207221, G2423387114, G2471646051, G2522063444, G2528027702, Indiana Clinical and Translational Sciences Institute, G2734643670, G2835601961, G29951154, Sensory and Perceptual Measures as Biomarkers of Alzheimer's Disease Pathology, G3015188539, G3130427885, G3131374986, G3146424788, G3216574877, G3429128133, G3553156159, G3582805754, G3705772492, G3710456697, G3752451908, G3870774570, G3908963977, G3943784146, G3966393351, G4106855496, G4119534169, Pharmacogenomics of Statin Therapy, G43180419, G4401988282, G4475667458, G4501223628, THE NCAA-DOD GRAND ALLIANCE: CONCUSSION ASSESSMENT, RESEARCH, AND EDUCATION (CARE) CONSORTIUM, G4669903861, G4800177743, G4860885537, G5207404921, G5209990037, G528601746, G5324093878, G5365730499, EFFECTS OF TRAUMATIC BRAIN INJURY (TBI) AND POST TRAUMATIC STRESS DISORDER (PTSD) ON ALZHEIMER'S DISEASE (AD) IN VETERANS USING IMAGING AND BIOMARKERS IN THE AD NEUROIMAGING INITIATIVE (ADNI)", G5389965057, G5654639750, G5692282101, G5740349702, Integrating Neuroimaging, Multi-omics, and Clinical Data in Complex Disease, G5850682332, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, G613619302, G6173816828, G6210868510, G6371410416, G6412110892, G6447063303, G6719828067, G6792506723, G6899163935, G6948409098, Bio-behavioral Research At The Intersection of Cancer and Aging, G710916345, G72415811, G7268282379, G7298697282, G7414321945, Memory Circuitry in MCI and Early Alzheimerâs Disease Prodrome: Molecular Drivers, G764699806, G7799614282, G781725486, G7880228552, G8107776361, G8219203717, G8228018387, G8243852412, G8281378126, G8301434335, G839208290, Neurogenesis in Adult Brain: Gene Networks and Alzheimer’s Disease, G859153142, G8852128998, G8895907669, G8897063270, Older Breast Cancer Patients: Risk For Cognitive Decline, G8957659042, G9000039018, G9000074849, G9000122335, Oregon Clinical and Translational Research Institute, G920654007
OpenAlex ID: W2980252792