Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals

Jason J. Corneveaux, Amanda J. Myers, April N. Allen, Jeremy J. Pruzin, Manuel Ramirez, Anzhelika Engel, Michael A. Nalls, Kewei Chen, Wendy Lee, Kendria Chewning, Stephen E. Villa, Hunsar B. Meechoovet, Jill D. Gerber, Danielle Frost, Hollie L. Benson, Sean O'Reilly, Lori B. Chibnik, Joshua M. Shulman, Andrew B. Singleton, David W. CraigKendall R. Van Keuren-Jensen, Travis Dunckley, David A. Bennett, Philip L. de Jager, Christopher Heward, John Hardy, Eric M. Reiman, Matthew J. Huentelman

Research output: Contribution to journalArticle

184 Scopus citations

Abstract

In this study, we assess 34 of the most replicated genetic associations for Alzheimer's disease (AD) using data generated on Affymetrix SNP 6.0 arrays and imputed at over 5.7 million markers from a unique cohort of over 1600 neuropathologically defined AD cases and controls (1019 cases and 591 controls). Testing the top genes from the AlzGene meta-analysis, we confirm the well-known association with APOE single nucleotide polymorphisms (SNPs), the CLU, PICALM and CR1 SNPs recently implicated in unusually large data sets, and previously implicated CST3 and ACE SNPs. In the cases of CLU, PICALM and CR1,aswell as in APOE, the odds ratios we find are slightly larger than those previously reported in clinical samples, consistent with what we believe to be more accurate classification of disease in the clinically characterized and neuropathologically confirmed AD cases and controls.

Original languageEnglish (US)
Article numberddq221
Pages (from-to)3295-3301
Number of pages7
JournalHuman molecular genetics
Volume19
Issue number16
DOIs
StatePublished - Jun 9 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Corneveaux, J. J., Myers, A. J., Allen, A. N., Pruzin, J. J., Ramirez, M., Engel, A., Nalls, M. A., Chen, K., Lee, W., Chewning, K., Villa, S. E., Meechoovet, H. B., Gerber, J. D., Frost, D., Benson, H. L., O'Reilly, S., Chibnik, L. B., Shulman, J. M., Singleton, A. B., ... Huentelman, M. J. (2010). Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals. Human molecular genetics, 19(16), 3295-3301. [ddq221]. https://doi.org/10.1093/hmg/ddq221