Journal Article

Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease

Ritchie, Karen, Combarros, Onofre, Hannequin, Didier, Engelborghs, Sebastiaan, Dufouil, Carole, Bettens, Karolien, Bossù, Paola, Annoni, Giorgio, Tzourio, Christophe, Franck, Ana, Licastro, Federico, Galimberti, Daniela, Letenneur, Luc, Berr, Claudine, De Deyn, Peter, Barberger-Gateau, Pascale, Helisalmi, Seppo, Sleegers, Kristel, Alvarez, Victoria, Porcellini, Elisa, Lathrop, Mark, Lendon, Corinne, Zelenika, Diana, Alpérovitch, Annick, Nacmias, Benedetta, Leveillard, Thierry, Amouyel, Philippe, Even, Gael, Soininen, Hilkka, Tavernier, Béatrice, de Pancorbo, Marian M, Bullido, Maria J, Mateo, Ignacio, Dartigues, Jean-François, Pasquier, Florence, Jaillard, Céline, Campion, Dominique, Piccardi, Paola, Hiltunen, Mikko, Gut, Ivo, Bosco, Paolo, Hanon, Olivier, Blanché, Hélène, Fiévet, Nathalie, Seripa, Davide, Van Broeckhoven, Christine, Heath, Simon, Lambert, Jean-Charles, Mancuso, Michelangelo, Panza, Francesco

2009

Overview

Philippe Amouyel and colleagues report a genome-wide association study for Alzheimer's disease. They identify variants within CLU and CR1 associated with susceptibility to late-onset Alzheimer's disease. The gene encoding apolipoprotein E ( APOE ) on chromosome 19 is the only confirmed susceptibility locus for late-onset Alzheimer's disease. To identify other risk loci, we conducted a large genome-wide association study of 2,032 individuals from France with Alzheimer's disease (cases) and 5,328 controls. Markers outside APOE with suggestive evidence of association ( P < 10 −5 ) were examined in collections from Belgium, Finland, Italy and Spain totaling 3,978 Alzheimer's disease cases and 3,297 controls. Two loci gave replicated evidence of association: one within CLU (also called APOJ ), encoding clusterin or apolipoprotein J, on chromosome 8 (rs11136000, OR = 0.86, 95% CI 0.81–0.90, P = 7.5 × 10 −9 for combined data) and the other within CR1 , encoding the complement component (3b/4b) receptor 1, on chromosome 1 (rs6656401, OR = 1.21, 95% CI 1.14–1.29, P = 3.7 × 10 −9 for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of β amyloid (Aβ) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimer's disease.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Adult and adolescent clinical studies / Agriculture / Alzheimer Disease - genetics / Alzheimer's disease / Animal Genetics and Genomics / Apolipoproteins / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Clusterin - genetics / Data analysis / Data collection / Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases / Demographic aspects / Disease susceptibility / European Continental Ancestry Group - genetics / Fundamental and applied biological sciences. Psychology / Gene Function / Genetic aspects / Genetic Predisposition to Disease / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Grants / Haplotypes / Health aspects / Human Genetics / Humans / letter / Medical research / Medical sciences / Neurological disorders / Neurology / Organic mental disorders. Neuropsychology / Physiological aspects / Polymorphism, Single Nucleotide / Psychology. Psychoanalysis. Psychiatry / Psychopathology. Psychiatry / Receptors, Complement 3b - genetics / Risk factors / Single nucleotide polymorphisms