Follow-Up Study of Susceptibility Loci for Alzheimer's Disease and Onset Age Identified by Genome-Wide Association

被引：26

作者：

Bettens, Karolien ^{[1
,2
,4
]}

Brouwers, Nathalie ^{[1
,2
,4
]}

Van Miegroet, Helen ^{[1
,2
,4
]}

Gil, Ana ^{[1
,2
,4
]}

Engelborghs, Sebastiaan ^{[3
,4
,5
,6
]}

De Deyn, Peter P. ^{[3
,4
,5
,6
]}

Vandenberghe, Rik ^{[7
,8
]}

Van Broeckhoven, Christine ^{[1
,2
,4
]}

Sleegers, Kristel ^{[1
,2
,4
]}

机构：

[1] Univ Antwerp VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, B-2610 Antwerp, Belgium

[2] Inst Born Bunge, Neurogenet Lab, Antwerp, Belgium

[3] Inst Born Bunge, Lab Neurochem & Behav, Antwerp, Belgium

[4] Univ Antwerp, B-2020 Antwerp, Belgium

[5] ZNA Middelheim, Memory Clin, Antwerp, Belgium

[6] ZNA Middelheim, Div Neurol, Antwerp, Belgium

[7] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium

[8] Univ Leuven KUL, Louvain, Belgium

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2010年 / 19卷 / 04期

关键词：

Alzheimer dementia; genome-wide association; onset age; replication; APOE EPSILON-4; VARIANTS; DEMENTIA; TRAITS; GENES; RISK; CLU;

D O I：

10.3233/JAD-2010-1310

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Replication of genetic association findings in independent studies represents an important validation tool in the search for susceptibility genes for complex diseases such as Alzheimer's disease (AD). In a well-characterized memory-clinic based study comprising 1078 unrelated AD patients and 652 control individuals, we set out to replicate previously reported genome-wide association of four novel risk SNPs with AD and onset age, with first stage p-values ranging from 0.001 to 0.000004. We obtained evidence for association between rs179943, an intronic SNP in ATXN1 at 6p22.3, and affection status (OR = 0.63 (95% CI = 0.44-0.90; nominal p = 0.01)). Overall, our data provided independent support for association of at least one chromosomal locus with AD and warranted a more in-depth investigation of these regions for possible underlying functional variants.

引用

页码：1169 / 1175

页数：7

共 21 条

[1] A genome-wide association study for late-onset Alzheimer's disease using DNA pooling [J].

Abraham, Richard ;

Moskvina, Valentina ;

Sims, Rebecca ;

Hollingworth, Paul ;

Morgan, Angharad ;

Georgieva, Lyudmila ;

Dowzell, Kimberley ;

Cichon, Sven ;

Hillmer, Axel M. ;

O'Donovan, Michael C. ;

Williams, Julie ;

Owen, Michael J. ;

Kirov, George .

BMC MEDICAL GENOMICS, 2008, 1 (1)

[2] Genome-wide Association Study Implicates a Chromosome 12 Risk Locus for Late-Onset Alzheimer Disease [J].

Beecham, Gary W. ;

Martin, Eden R. ;

Li, Yi-Ju ;

Slifer, Michael A. ;

Gilbert, John R. ;

Haines, Jonathan L. ;

Pericak-Vance, Margaret A. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (01) :35-43

[3] Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE [J].

Bertram, Lars ;

Lange, Christoph ;

Mullin, Kristina ;

Parkinson, Michele ;

Hsiao, Monica ;

Hogan, Meghan F. ;

Schjeide, Brit M. M. ;

Hooli, Basavaraj ;

DiVito, Jason ;

Ionita, Luliana ;

Jiang, Hongyu ;

Laird, Nan ;

Moscarillo, Thomas ;

Ohlsen, Kari L. ;

Elliott, Kathryn ;

Wang, Xin ;

Hu-Lince, Diane ;

Ryder, Marie ;

Murphy, Amy ;

Wagner, Steven L. ;

Blacker, Deborah ;

Becker, K. David ;

Tanzi, Rudolph E. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 83 (05) :623-632

[4] Genetic risk and transcriptional variability of amyloid precursor protein in Alzheimer's disease [J].

Brouwers, Nathalie ;

Sleegers, Kristel ;

Engelborghs, Sebastiaan ;

Bogaerts, Veerle ;

Serneels, Sally ;

Kamali, Kenan ;

Corsmit, Ellen ;

De Leenheir, Evelyn ;

Martin, Jean-Jacques ;

De Deyn, Peter P. ;

Van Broeckhoven, Christine ;

Theuns, Jessie .

BRAIN, 2006, 129 :2984-2991

[5] Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease [J].

Carrasquillo, Minerva M. ;

Zou, Fanggeng ;

Pankratz, V. Shane ;

Wilcox, Samantha L. ;

Ma, Li ;

Walker, Louise P. ;

Younkin, Samuel G. ;

Younkin, Curtis S. ;

Younkin, Linda H. ;

Bisceglio, Gina D. ;

Ertekin-Taner, Nilufer ;

Crook, Julia E. ;

Dickson, Dennis W. ;

Petersen, Ronald C. ;

Graff-Radford, Neill R. ;

Younkin, Steven G. .

NATURE GENETICS, 2009, 41 (02) :192-198

[6] Dose dependent effect of APOE ε4 on behavioral symptoms in frontal lobe dementia [J].

Engelborghs, S ;

Dermaut, B ;

Mariën, P ;

Symons, A ;

Vloeberghs, E ;

Maertens, K ;

Somers, N ;

Goeman, J ;

Rademakers, R ;

Van den Broeck, M ;

Pickut, B ;

Cruts, M ;

Van Broeckhoven, C ;

De Deyn, PP .

NEUROBIOLOGY OF AGING, 2006, 27 (02) :285-292

[7] Prospective Belgian study of neurodegenerative and vascular dementia:: APOE genotype effects [J].

Engelborghs, S ;

Dermaut, B ;

Goeman, J ;

Saerens, J ;

Mariën, P ;

Pickut, BA ;

Van den Broeck, M ;

Serneels, S ;

Cruts, M ;

Van Broeckhoven, C ;

De Deyn, PP .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2003, 74 (08) :1148-1151

[8] MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN [J].

FOLSTEIN, MF ;

FOLSTEIN, SE ;

MCHUGH, PR .

JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) :189-198

[9] Role of genes and environments for explaining Alzheimer disease [J].

Gatz, M ;

Reynolds, CA ;

Fratiglioni, L ;

Johansson, B ;

Mortimer, JA ;

Berg, S ;

Fiske, A ;

Pedersen, NL .

ARCHIVES OF GENERAL PSYCHIATRY, 2006, 63 (02) :168-174

[10] Evidence for novel susceptibility genes for late-onset Alzheimer's disease from a genome-wide association study of putative functional variants [J].

Grupe, Andrew ;

Abraham, Richard ;

Li, Yonghong ;

Rowland, Charles ;

Hollingworth, Paul ;

Morgan, Angharad ;

Jehu, Luke ;

Segurado, Ricardo ;

Stone, David ;

Schadt, Eric ;

Karnoub, Maha ;

Nowotny, Petra ;

Tacey, Kristina ;

Catanese, Joseph ;

Sninsky, John ;

Brayne, Carol ;

Rubinsztein, David ;

Gill, Michael ;

Lawlor, Brian ;

Lovestone, Simon ;

Holmans, Peter ;

O'Donovan, Michael ;

Morris, John C. ;

Thal, Leon ;

Goate, Alison ;

Owen, Michael J. ;

Williams, Julie .

HUMAN MOLECULAR GENETICS, 2007, 16 (08) :865-873

← 1 2 3 →