Integrated copy number and gene expression analysis detects a CREB1 association with Alzheimer's disease

被引：15

作者：

Li, Y. ^{[1
]}

Shaw, C. A. ^{[2
]}

Sheffer, I. ^{[1
]}

Sule, N. ^{[3
]}

Powell, S. Z. ^{[4
]}

Dawson, B. ^{[2
,5
]}

Zaidi, S. N. Y. ^{[1
]}

Bucasas, K. L. ^{[6
]}

Lupski, J. R. ^{[2
,7
]}

Wilhelmsen, K. C. ^{[8
]}

Doody, R. ^{[1
]}

Szigeti, K. ^{[1
,9
]}

机构：

[1] Baylor Coll Med, Dept Neurol, Alzheimers Dis & Memory Disorders Ctr, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA

[4] Methodist Hosp, Dept Neuropathol, Houston, TX 77030 USA

[5] Howard Hughes Med Inst, Houston, TX 77030 USA

[6] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA

[7] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[8] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA

[9] SUNY Buffalo, Dept Neurol, Buffalo, NY 14203 USA

来源：

TRANSLATIONAL PSYCHIATRY | 2012年 / 2卷

关键词：

Alzheimer's disease; eQTL; multi-omics; GENOME-WIDE ASSOCIATION; ILLUMINA MICROARRAY; IDENTIFIES VARIANTS; MUTATION SPECTRUM; PREVALENCE; DEMENTIA; MEMORY; ENHANCEMENT; INFORMATION; SEQUENCE;

D O I：

10.1038/tp.2012.119

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Genetic variation, both single-nucleotide variations and copy number variations (CNV), contribute to changes in gene expression. In some cases these variations are meaningfully correlated with disease states. We hypothesized that in a genetically heterogeneous disorder such as sporadic Alzheimer's disease ( AD), utilizing gene expression as a quantitative trait and CNVs as a genetic marker map within the same individuals in the context of case-control status may increase the power to detect relevant loci. Using this approach an 8-kb deletion was identified that contains a PAX6-binding site on chr2q33.3 upstream of CREB1 encoding the cAMP responsive element-binding protein1 transcription factor. The association of the CNV to AD was confirmed by a case-control association study consisting of the Texas Alzheimer Research and Care Consortium and NIA-LOAD Family Study data sets.

引用

页码：e192 / e192

页数：8

共 39 条

[1]

Barco A, 2003, EXPERT OPIN THER TAR, V7, P101, DOI 10.1517/14728222.7.1.101

[2] CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation [J].

Bartsch, D ;

Casadio, A ;

Karl, KA ;

Serodio, P ;

Kandel, ER .

CELL, 1998, 95 (02) :211-223

[3] Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence [J].

Benko, Sabina ;

Fantes, Judy A. ;

Amiel, Jeanne ;

Kleinjan, Dirk-Jan ;

Thomas, Sophie ;

Ramsay, Jacqueline ;

Jamshidi, Negar ;

Essafi, Abdelkader ;

Heaney, Simon ;

Gordon, Christopher T. ;

McBride, David ;

Golzio, Christelle ;

Fisher, Malcolm ;

Perry, Paul ;

Abadie, Veronique ;

Ayuso, Carmen ;

Holder-Espinasse, Muriel ;

Kilpatrick, Nicky ;

Lees, Melissa M. ;

Picard, Arnaud ;

Temple, I. Karen ;

Thomas, Paul ;

Vazquez, Marie-Paule ;

Vekemans, Michel ;

Roest Crollius, Hugues ;

Hastie, Nicholas D. ;

Munnich, Arnold ;

Etchevers, Heather C. ;

Pelet, Anna ;

Farlie, Peter G. ;

FitzPatrick, David R. ;

Lyonnet, Stanislas .

NATURE GENETICS, 2009, 41 (03) :359-364

[4] Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b/C4b binding sites [J].

Brouwers, N. ;

Van Cauwenberghe, C. ;

Engelborghs, S. ;

Lambert, J-C ;

Bettens, K. ;

Le Bastard, N. ;

Pasquier, F. ;

Montoya, A. Gil ;

Peeters, K. ;

Mattheijssens, M. ;

Vandenberghe, R. ;

De Deyn, P. P. ;

Cruts, M. ;

Amouyel, P. ;

Sleegers, K. ;

Van Broeckhoven, C. .

MOLECULAR PSYCHIATRY, 2012, 17 (02) :223-233

[5] Early-onset autosomal dominant Alzheimer disease: Prevalence, genetic heterogeneity, and mutation spectrum [J].

Campion, D ;

Dumanchin, C ;

Hannequin, D ;

Dubois, B ;

Belliard, S ;

Puel, M ;

Thomas-Anterion, C ;

Michon, A ;

Martin, C ;

Charbonnier, F ;

Raux, G ;

Camuzat, A ;

Penet, C ;

Mesnage, V ;

Martinez, M ;

Clerget-Darpoux, F ;

Brice, A ;

Frebourg, T .

AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (03) :664-670

[6] Mutation spectrum revealed by breakpoint sequencing of human germline CNVs [J].

Conrad, Donald F. ;

Bird, Christine ;

Blackburne, Ben ;

Lindsay, Sarah ;

Mamanova, Lira ;

Lee, Charles ;

Turner, Daniel J. ;

Hurles, Matthew E. .

NATURE GENETICS, 2010, 42 (05) :385-U43

[7] The number of trait loci in late-onset Alzheimer disease [J].

Daw, EW ;

Payami, H ;

Nemens, EJ ;

Nochlin, D ;

Bird, TD ;

Schellenberg, GD ;

Wijsman, EM .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (01) :196-204

[8] Multipoint oligogenic analysis of age-at-onset data with applications to Alzheimer disease pedigrees [J].

Daw, EW ;

Heath, SC ;

Wijsman, EM .

AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (03) :839-851

[9] lumi:: a pipeline for processing Illumina microarray [J].

Du, Pan ;

Kibbe, Warren A. ;

Lin, Simon M. .

BIOINFORMATICS, 2008, 24 (13) :1547-1548

[10] PREVALENCE AND TYPES OF DEMENTIA IN THE VERY OLD - RESULTS FROM THE CANADIAN-STUDY-OF-HEALTH-AND-AGING [J].

EBLY, EM ;

PARHAD, IM ;

HOGAN, DB ;

FUNG, TS .

NEUROLOGY, 1994, 44 (09) :1593-1600

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