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

Abstract

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 x 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 x 10(-9) for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of beta amyloid (Abeta) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimer's disease.

• Authors: Jean-Charles Lambert, Simon Heath, Gael Even, Dominique Campion, Kristel Sleegers, Mikko Hiltunen, Onofre Combarros, Diana Zelenika, Maria J Bullido, Béatrice Tavernier, Luc Letenneur, Karolien Bettens, Claudine Berr, Florence Pasquier, Nathalie Fiévet, Pascale Barberger-Gateau, Sebastiaan Engelborghs, Peter De Deyn, Ignacio Mateo, Ana Franck, Seppo Helisalmi, Elisa Porcellini, Olivier Hanon, European Alzheimer's Disease Initiative Investigators, Marian M de Pancorbo, Corinne Lendon, Carole Dufouil, Céline Jaillard, Thierry Leveillard, Victoria Alvarez, Paolo Bosco, Michelangelo Mancuso, Francesco Panza, Benedetta Nacmias, Paola Bossù, Paola Piccardi, Giorgio Annoni, Davide Seripa, Daniela Galimberti, Didier Hannequin, Federico Licastro, Hilkka Soininen, Karen Ritchie, Hélène Blanché, Jean-François Dartigues, Christophe Tzourio, Ivo Gut, Christine Van Broeckhoven, Annick Alpérovitch, Mark Lathrop, Philippe Amouyel
• Journal: Nature genetics (Nat Genet) Vol. 41 Issue 10 Pg. 1094-9 (Oct 2009) ISSN: 1546-1718 [Electronic] United States
• PMID: 19734903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLU protein, human
• CR1 protein, human
• Clusterin
• Receptors, Complement 3b

Topics

• Alzheimer Disease (genetics)
• Clusterin (genetics)
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Haplotypes
• Humans
• Polymorphism, Single Nucleotide
• Receptors, Complement 3b (genetics)
• White People (genetics)