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

Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Lambert, J., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., Tavernier, B., Letenneur, L., Bettens, K., Berr, C., Pasquier, F., Fiévet, N., Barberger-Gateau, P., Engelborghs, S., De Deyn, P., Mateo, I., Franck, A., Helisalmi, S., Porcellini, E., Hanon, O., European Alzheimer's Disease Initiative Investigators, de Pancorbo, M. M., Lendon, C., Dufouil, C., Jaillard, C., Leveillard, T., Alvarez, V., Bosco, P., Mancuso, M., Panza, F., Nacmias, B., Bossù, P., Piccardi, P., Annoni, G., Seripa, D., Galimberti, D., Hannequin, D., Licastro, F., Soininen, H., Ritchie, K., Blanché, H., Dartigues, J., Tzourio, C., Gut, I., Van Broeckhoven, C., Alpérovitch, A., Lathrop, M., & Amouyel, P. Nature Genetics, 41(10):1094–1099, October, 2009.
doi abstract bibtex

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 \textless 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.

@article{lambert_genome-wide_2009,
	title = {Genome-wide association study identifies variants at {CLU} and {CR1} associated with {Alzheimer}'s disease},
	volume = {41},
	issn = {1546-1718},
	doi = {10.1038/ng.439},
	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 {\textless} 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.},
	language = {eng},
	number = {10},
	journal = {Nature Genetics},
	author = {Lambert, Jean-Charles and Heath, Simon and Even, Gael and Campion, Dominique and Sleegers, Kristel and Hiltunen, Mikko and Combarros, Onofre and Zelenika, Diana and Bullido, Maria J. and Tavernier, Béatrice and Letenneur, Luc and Bettens, Karolien and Berr, Claudine and Pasquier, Florence and Fiévet, Nathalie and Barberger-Gateau, Pascale and Engelborghs, Sebastiaan and De Deyn, Peter and Mateo, Ignacio and Franck, Ana and Helisalmi, Seppo and Porcellini, Elisa and Hanon, Olivier and {European Alzheimer's Disease Initiative Investigators} and de Pancorbo, Marian M. and Lendon, Corinne and Dufouil, Carole and Jaillard, Céline and Leveillard, Thierry and Alvarez, Victoria and Bosco, Paolo and Mancuso, Michelangelo and Panza, Francesco and Nacmias, Benedetta and Bossù, Paola and Piccardi, Paola and Annoni, Giorgio and Seripa, Davide and Galimberti, Daniela and Hannequin, Didier and Licastro, Federico and Soininen, Hilkka and Ritchie, Karen and Blanché, Hélène and Dartigues, Jean-François and Tzourio, Christophe and Gut, Ivo and Van Broeckhoven, Christine and Alpérovitch, Annick and Lathrop, Mark and Amouyel, Philippe},
	month = oct,
	year = {2009},
	pmid = {19734903},
	keywords = {Alzheimer Disease, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, Polymorphism, Single Nucleotide, Clusterin, European Continental Ancestry Group, Receptors, Complement 3b},
	pages = {1094--1099}
}

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