Meta-analysis of Alzheimer’s disease on 9,751 samples from Norway and IGAP study identifies four risk loci
Year: 2018
Type: review
Study design: Observational Study
Abstract: A large fraction of genetic risk factors for Alzheimer’s Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed a meta-analysis using GWAS results from 2,893 AD cases and 6,858 cognitively normal controls from Norway and 25,580 cases and 48,466 controls from the International Genomics of Alzheimer’s Project (IGAP), denoted the discovery sample. Second, we selected the top hits (p < 1 × 10−6) from the discovery analysis for replication in an Icelandic cohort consisting of 5,341 cases and 110,008 controls. We identified a novel genomic region with genome-wide significant association with AD on chromosome 4 (combined analysis OR = 1.07, p = 2.48 x 10-8). This finding implicatedHS3ST1, a gene expressed throughout the brain particularly in the cerebellar cortex. In addition, we identifiedIGHV1-68in the discovery sample, previously not associated with AD. We also associatedUSP6NL/ECHDC3andBZRAP1-AS1to AD, confirming findings from a follow-up transethnic study. These new gene loci provide further evidence for AD as a polygenic disorder, and suggest new mechanistic pathways that warrant further investigation.
Source: Scientific Reports
Authors: Aree Witoelar, Arvid Rongve, Ina S. Almdahl, Ingun D. Ulstein, Andreas Engvig, Linda R. White, Geir Selbæk, Eystein Stordal, Fred Andersen, Anne Brækhus, Ingvild Saltvedt, Knut Engedal, Timothy Hughes, Sverre Bergh, Geir Bråthen, Nenad Bogdanovic, Francesco Bettella, Yunpeng Wang, Lavinia Athanasiu, Shahram Bahrami, Stephanie Le Hellard, Sudheer Giddaluru, Anders M. Dale, Sigrid B. Sando, Stacy Steinberg, Hreinn Stefansson, Jon Snaedal, Rahul S. Desikan, Kari Stefansson, Dag Aarsland, Srdjan Djurovic, Tormod Fladby, Ole A. Andreassen
Institutions: Oslo University Hospital, University of Oslo, Fonna Hospital Trust, University of Bergen, Akershus University Hospital, Norwegian University of Science and Technology, St Olav's University Hospital, Sykehuset i Vestfold, Norwegian National Centre for Ageing and Health, Namsos Hospital, UiT The Arctic University of Norway, Innlandet Hospital Trust, Haukeland University Hospital, University of California San Diego, deCODE Genetics (Iceland), National University Hospital of Iceland, University of California, San Francisco, King's College London, Stavanger University Hospital
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: Alzheimer's Association, Wellcome Trust, EU Joint Programme – Neurodegenerative Disease Research, Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease, Université de Lille, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Bundesministerium für Bildung und Forschung, Erasmus Medisch Centrum, Norges Forskningsråd, Hjartavernd, Nasjonalforeningen for Folkehelsen, Centre hospitalier régional universitaire de Lille, National Institutes of Health, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute
Awards: G1108310052, G1173778324, Kompetenznetz 'Demenzen', G1445512935, G1901425420, G2193588257, G230712557, G2413885692, G2697093250, G2929235049, G3161882281, G3277956970, National Alzheimer's Coordinating Center, Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime, G3386955339, G3402222819, G3433676821, G346328595, G3553495277, G3751924189, G3916087950, G3926333944, G4018065756, G4261582792, G4838234079, Psychiatric Diagnostic and Prevention Consortium, Alzheimer's Disease Genetics Consortium, G5558075022, G5760312152, CHARGE consortium: omics discovery for CVD and aging phenotypes, User-friendly ICT tools to enhance self-management and effective treatment of depression in the EU, A Powerful, Genome-Wide Association Scan for Susceptibility Genes for late-onset Alzheimer's disease, Verbundprojekt: Kompetenznetz Demenzen - Epidemiologie: Teilprojekte der Universität Bonn, G6425121803, G6648385527, G6708752960, Verbundprojekt Kompetenznetz Demenzen: Teilprojekte des ZISG Mannheim (2. Förderphase), G7373387228, G7431531211, G8270261256, AD Gene Discovery: Exome Chip, New Endophenotypes & Functional Studies in CHARGE, G8506111834, G853614028, Marie Curie cofunding of the FRICON mobility programme in the Research Council of Norway scheme for independent basic research projects, G863491659, G8858095331, G8951052545, G9000030076, National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)
OpenAlex ID: W2905897012