Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control study

被引：59

作者：

Carrasquillo, Minerva M. ^{[1
]}

Belbin, Olivia ^{[1
,2
]}

Hunter, Talisha A. ^{[1
]}

Ma, Li ^{[1
]}

Bisceglio, Gina D. ^{[1
]}

Zou, Fanggeng ^{[1
]}

Crook, Julia E. ^{[4
]}

Pankratz, V. Shane ^{[3
]}

Sando, Sigrid B. ^{[5
,6
]}

Aasly, Jan O. ^{[5
,6
]}

Barcikowska, Maria ^{[7
]}

Wszolek, Zbigniew K. ^{[8
]}

Dickson, Dennis W. ^{[1
]}

Graff-Radford, Neill R. ^{[1
,8
]}

Petersen, Ronald C. ^{[9
,10
]}

Passmore, Peter ^{[11
]}

Morgan, Kevin ^{[2
]}

Younkin, Steven G. ^{[1
]}

机构：

[1] Mayo Clin Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA

[2] Univ Nottingham, Queenss Med Ctr, Inst Genet, Sch Mol Med Sci, Nottingham NG7 2UH, England

[3] Mayo Clin Coll Med, Div Biomed Stat & Informat, Rochester, MN 55905 USA

[4] Mayo Clin Coll Med, Biostat Unit, Jacksonville, FL 32224 USA

[5] St Olavs Hosp, Dept Neurol, N-7006 Trondheim, Norway

[6] Norwegian Univ Sci & Technol, NTNU, Dept Neurosci, N-7491 Trondheim, Norway

[7] Polish Acad Sci, Med Res Ctr, Dept Neurodegenerat Disorders, Warsaw, Poland

[8] Mayo Clin Coll Med, Dept Neurol, Jacksonville, FL 32224 USA

[9] Mayo Clin Coll Med, Dept Neurol, Rochester, MN 55905 USA

[10] Mayo Clin Coll Med, Mayo Alzheimer Dis Res Ctr, Rochester, MN 55905 USA

[11] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Publ Hlth, Belfast BT7 1NN, Antrim, North Ireland

来源：

MOLECULAR NEURODEGENERATION | 2011年 / 6卷

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; COMPLEMENT RECEPTOR 1; IDENTIFIES VARIANTS; COMMON VARIANTS; CLU; PICALM; RISK; CR-1; POLYMORPHISMS; LOCI;

D O I：

10.1186/1750-1326-6-54

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near MS4A4A, CD2AP, EPHA1 and CD33. Meta-analyses of this and a previously published GWAS revealed significant association at ABCA7 and MS4A, independent evidence for association of CD2AP, CD33 and EPHA1 and an opposing yet significant association of a variant near ARID5B. In this study, we genotyped five variants (in or near CD2AP, EPHA1, ARID5B, and CD33) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE epsilon 4 dosage. Results: We found no significant evidence of series heterogeneity. Associations with LOAD were successfully replicated for EPHA1 (rs11767557; OR = 0.87, p = 5 x 10(-4)) and CD33 (rs3865444; OR = 0.92, p = 0.049), with odds ratios comparable to those previously reported. Although the two ARID5B variants (rs2588969 and rs494288) showed significant association with LOAD in meta-analysis of our dataset (p = 0.046 and 0.008, respectively), the associations did not survive adjustment for covariates (p = 0.30 and 0.11, respectively). We had insufficient evidence in our data to support the association of the CD2AP variant (rs9349407, p = 0.56). Conclusions: Our data overwhelmingly support the association of EPHA1 and CD33 variants with LOAD risk: addition of our data to the results previously reported (total n > 42,000) increased the strength of evidence for these variants, providing impressive p-values of 2.1 x 10(-15) (EPHA1) and 1.8 x 10(-13) (CD33).

引用

页数：9

共 25 条

[1]

[Anonymous], MOL PSYCHIAT

[2] Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease [J].

Belbin, Olivia ;

Carrasquillo, Minerva M. ;

Crump, Michael ;

Culley, Oliver J. ;

Hunter, Talisha A. ;

Ma, Li ;

Bisceglio, Gina ;

Zou, Fanggeng ;

Allen, Mariet ;

Dickson, Dennis W. ;

Graff-Radford, Neill R. ;

Petersen, Ronald C. ;

Morgan, Kevin ;

Younkin, Steven G. .

HUMAN GENETICS, 2011, 129 (03) :273-282

[3] Replication of CLU, CR1, and PICALM Associations With Alzheimer Disease [J].

Carrasquillo, Minerva M. ;

Belbin, Olivia ;

Hunter, Talisha A. ;

Ma, Li ;

Bisceglio, Gina D. ;

Zou, Fanggeng ;

Crook, Julia E. ;

Pankratz, V. Shane ;

Dickson, Dennis W. ;

Graff-Radford, Neill R. ;

Petersen, Ronald C. ;

Morgan, Kevin ;

Younkin, Steven G. .

ARCHIVES OF NEUROLOGY, 2010, 67 (08) :961-964

[4]

CARRASQUILLO MM, 2011, J ALZHEIMERS DIS

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

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. .

HUMAN MOLECULAR GENETICS, 2010, 19 (16) :3295-3301

[6] METAANALYSIS IN CLINICAL-TRIALS [J].

DERSIMONIAN, R ;

LAIRD, N .

CONTROLLED CLINICAL TRIALS, 1986, 7 (03) :177-188

[7] Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease [J].

Harold, Denise ;

Abraham, Richard ;

Hollingworth, Paul ;

Sims, Rebecca ;

Gerrish, Amy ;

Hamshere, Marian L. ;

Pahwa, Jaspreet Singh ;

Moskvina, Valentina ;

Dowzell, Kimberley ;

Williams, Amy ;

Jones, Nicola ;

Thomas, Charlene ;

Stretton, Alexandra ;

Morgan, Angharad R. ;

Lovestone, Simon ;

Powell, John ;

Proitsi, Petroula ;

Lupton, Michelle K. ;

Brayne, Carol ;

Rubinsztein, David C. ;

Gill, Michael ;

Lawlor, Brian ;

Lynch, Aoibhinn ;

Morgan, Kevin ;

Brown, Kristelle S. ;

Passmore, Peter A. ;

Craig, David ;

McGuinness, Bernadette ;

Todd, Stephen ;

Holmes, Clive ;

Mann, David ;

Smith, A. David ;

Love, Seth ;

Kehoe, Patrick G. ;

Hardy, John ;

Mead, Simon ;

Fox, Nick ;

Rossor, Martin ;

Collinge, John ;

Maier, Wolfgang ;

Jessen, Frank ;

Schuermann, Britta ;

van den Bussche, Hendrik ;

Heuser, Isabella ;

Kornhuber, Johannes ;

Wiltfang, Jens ;

Dichgans, Martin ;

Froelich, Lutz ;

Hampel, Harald ;

Huell, Michael .

NATURE GENETICS, 2009, 41 (10) :1088-U61

[8] Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease [J].

Hollingworth, Paul ;

Harold, Denise ;

Sims, Rebecca ;

Gerrish, Amy ;

Lambert, Jean-Charles ;

Carrasquillo, Minerva M. ;

Abraham, Richard ;

Hamshere, Marian L. ;

Pahwa, Jaspreet Singh ;

Moskvina, Valentina ;

Dowzell, Kimberley ;

Jones, Nicola ;

Stretton, Alexandra ;

Thomas, Charlene ;

Richards, Alex ;

Ivanov, Dobril ;

Widdowson, Caroline ;

Chapman, Jade ;

Lovestone, Simon ;

Powell, John ;

Proitsi, Petroula ;

Lupton, Michelle K. ;

Brayne, Carol ;

Rubinsztein, David C. ;

Gill, Michael ;

Lawlor, Brian ;

Lynch, Aoibhinn ;

Brown, Kristelle S. ;

Passmore, Peter A. ;

Craig, David ;

McGuinness, Bernadette ;

Todd, Stephen ;

Holmes, Clive ;

Mann, David ;

Smith, A. David ;

Beaumont, Helen ;

Warden, Donald ;

Wilcock, Gordon ;

Love, Seth ;

Kehoe, Patrick G. ;

Hooper, Nigel M. ;

Vardy, Emma R. L. C. ;

Hardy, John ;

Mead, Simon ;

Fox, Nick C. ;

Rossor, Martin ;

Collinge, John ;

Maier, Wolfgang ;

Jessen, Frank ;

Ruether, Eckart .

NATURE GENETICS, 2011, 43 (05) :429-+

[9] Meta-Analysis for Genome-Wide Association Study Identifies Multiple Variants at the BIN1 Locus Associated with Late-Onset Alzheimer's Disease [J].

Hu, Xiaolan ;

Pickering, Eve ;

Liu, Yingxue Cathy ;

Hall, Stephanie ;

Fournier, Helene ;

Katz, Elyse ;

Dechairo, Bryan ;

John, Sally ;

Van Eerdewegh, Paul ;

Soares, Holly .

PLOS ONE, 2011, 6 (02)

[10] Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes [J].

Jun, Gyungah ;

Naj, Adam C. ;

Beecham, Gary W. ;

Wang, Li-San ;

Buros, Jacqueline ;

Gallins, Paul J. ;

Buxbaum, Joseph D. ;

Ertekin-Taner, Nilufer ;

Fallin, Daniele ;

Friedland, Robert ;

Inzelberg, Rivka ;

Kramer, Patricia ;

Rogaeva, Ekaterina ;

George-Hyslop, Peter St. ;

Cantwell, Laura B. ;

Dombroski, Beth A. ;

Saykin, Andrew J. ;

Reiman, Eric M. ;

Bennett, David A. ;

Morris, John C. ;

Lunetta, Kathryn L. ;

Martin, Eden R. ;

Montine, Thomas J. ;

Goate, Alison M. ;

Blacker, Deborah ;

Tsuang, Debby W. ;

Beekly, Duane ;

Cupples, L. Adrienne ;

Hakonarson, Hakon ;

Kukull, Walter ;

Foroud, Tatiana M. ;

Haines, Jonathan ;

Mayeux, Richard ;

Farrer, Lindsay A. ;

Pericak-Vance, Margaret A. ;

Schellenberg, Gerard D. .

ARCHIVES OF NEUROLOGY, 2010, 67 (12) :1473-1484

← 1 2 3 →