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 language | English (US) |
|---|---|
| Article number | ddq221 |
| Pages (from-to) | 3295-3301 |
| Number of pages | 7 |
| Journal | Human Molecular Genetics |
| Volume | 19 |
| Issue number | 16 |
| DOIs | |
| State | Published - Jun 9 2010 |
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)
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Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals. / Corneveaux, Jason J.; Myers, Amanda J.; Allen, April N.; Pruzin, Jeremy J.; Ramirez, Manuel; Engel, Anzhelika; Nalls, Michael A.; Chen, Kewei; Lee, Wendy; Chewning, Kendria; Villa, Stephen E.; Meechoovet, Hunsar B.; Gerber, Jill D.; Frost, Danielle; Benson, Hollie L.; O'Reilly, Sean; Chibnik, Lori B.; Shulman, Joshua M.; Singleton, Andrew B.; Craig, David W.; Van Keuren-Jensen, Kendall R.; Dunckley, Travis; Bennett, David A.; de Jager, Philip L.; Heward, Christopher; Hardy, John; Reiman, Eric M.; Huentelman, Matthew J.
In: Human Molecular Genetics, Vol. 19, No. 16, ddq221, 09.06.2010, p. 3295-3301.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals
AU - Corneveaux, Jason J.
AU - Myers, Amanda J.
AU - Allen, April N.
AU - Pruzin, Jeremy J.
AU - Ramirez, Manuel
AU - Engel, Anzhelika
AU - Nalls, Michael A.
AU - Chen, Kewei
AU - Lee, Wendy
AU - Chewning, Kendria
AU - Villa, Stephen E.
AU - Meechoovet, Hunsar B.
AU - Gerber, Jill D.
AU - Frost, Danielle
AU - Benson, Hollie L.
AU - O'Reilly, Sean
AU - Chibnik, Lori B.
AU - Shulman, Joshua M.
AU - Singleton, Andrew B.
AU - Craig, David W.
AU - Van Keuren-Jensen, Kendall R.
AU - Dunckley, Travis
AU - Bennett, David A.
AU - de Jager, Philip L.
AU - Heward, Christopher
AU - Hardy, John
AU - Reiman, Eric M.
AU - Huentelman, Matthew J.
N1 - Funding Information: This work was supported by Kronos Science; The National Institute of Neurological Disorders and Stroke (R01 NS059873 to M.J.H.); The National Institute on Aging (R01 AG031581 to E.M.R.; P30 AG19610 to E.M.R.; AG034504 to A.J.M.; Z01 AG000950-06, P30AG10161 and R01AG 15819 to D.A.B.; and K01AG024079 to T.D.); The Banner Alzheimer’s Foundation; The Johnnie B. Byrd Sr. Alzheimer’s Disease Institute; The Medical Research Council (to J.H.); The Intramural Research Program of the National Institutes of Health; and the State of Arizona. Biomaterials were collected from several National Institute on Aging and National Alzheimer’s Coordinating Center (U01 AG016976) funded sites. Mar-celle Morrison-Bogorad, PhD, Tony Phelps, PhD and Walter Kukull, PhD are thanked for helping to co-ordinate this collection. The directors, pathologist and technicians involved include: National Institute on Aging; Ruth Seemann, John Hopkins Alzheimer’s Disease Research Center (NIA grant no. AG05146); Juan C. Troncoso, MD, Dr Olga Pletnikova, University of California, Los Angeles (NIA grant no. P50 AG16570); Harry Vinters, MD, Justine Pomakian, The Kathleen Price Bryan Brain Bank, Duke University Medical Center (NIA grant no. AG05128 and NIA P30 #AG028377, NINDS grant no. NS39764, NIMH MH60451 also funded by Glaxo Smith Kline); Christine Hulette, MD, Director, John F. Ervin, Stanford University; Dikran Horoupian, MD, Ahmad Salehi, MD, PhD, New York Brain Bank, Taub Institute, Columbia University (NYBB); Jean Paul Vonsattel, MD, Katerina Mancevska, Massachusetts General Hospital; E. Tessa Hedley-Whyte, MD, Dr M.P. Frosch, Karlotta Fitch (NIH grant P50 AG005134), University of Michigan (NIH grant P50-AG08671); Dr Roger Albin, Lisa Bain, Eszter Gombosi, University of Kentucky (NIH no. AG05144): William Markesbery, MD, Sonya Anderson, Mayo Clinic, Jacksonville; Dennis W. Dickson, MD, Natalie Thomas, University Southern California; Caroll A. Miller, MD, Jenny Tang, M.S., Dimitri Diaz, Washington University, St Louis Alzheimer’s Disease Research Center (NIH no. P50AG05681): Dan McKeel, MD, John C. Morris, MD, Eugene Johnson, Jr, PhD, Virginia Buckles, PhD, Deborah Carter, University of Washington, Seattle (NIH no. P50 AG05136); Thomas Montine, MD, PhD, Aimee Schantz, MD, Ann C. McKee, Carol Kubilus Sun Health Research Institute, Arizona (NIA no. P30 AG19610); Joseph Rogers, PhD, Thomas G. Beach, MD, PhD, Lucia I. Sue Emory University; Bruce H. Wainer, MD, PhD, Marla Gearing, PhD, University of Texas, Southwestern Medical School; Charles L. White, III, MD, Roger Rosenberg, Marilyn Howell, Joan Reisch, University of California, Davis; William Ellis, MD, Mary Ann Jarvis, Rush University Medical Center, Rush Alzheimer’s Disease Center (NIH no. P30AG10161); David A. Bennett, MD, Julie A. Schneider, MD, MS, Karen Skish, MS, PA (ASCP)MT, Wayne T Longman, University of Miami/NPF Brain Endowment Bank; Deborah C. Mash, MD, Margaret J. Basile, Mitsuko Tanaka Oregon Health & Science University; Randy Wotljer, PhD, additional tissues include samples from the following sites; Newcastle Brain Tissue Resource (funding via the UK Medical Research Council, local NHS trusts and Newcastle University); C.M. Morris, PhD, Ian G McKeith (Tissue for this study was provided by the Newcastle Brain Tissue Resource which is funded in part by a grant from the UK Medical Research Council (G0400074), by the Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases to the Newcastle upon Tyne Hospitals NHS Foundation Trust and by a grant from the Alzheimer’s Society and Alzheimer’s Research Trust as part of the Brains for Dementia Research Project); the MRC London Brain Bank for Neurodegenerative Diseases; Simon Lovestone, MD PhD, Safa Al-Sarraj, MD, Claire Troakes, South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England (HEFCE), Alzheimer’s Research Trust (ART), BRACE as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN); Seth Love, MD, Patrick Kehoe, PhD, Laura Palmer, The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onder-zoek); Inge Huitinga, MD, Marleen Rademaker, Michiel Koore-man, Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona; Isidre Ferrer Abizanda, MD, PhD, Susana Casas Boluda.
PY - 2010/6/9
Y1 - 2010/6/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77955036445&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955036445&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddq221
DO - 10.1093/hmg/ddq221
M3 - Article
C2 - 20534741
AN - SCOPUS:77955036445
VL - 19
SP - 3295
EP - 3301
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 16
M1 - ddq221
ER -