Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease

被引：36

作者：

Morgan, A. R. ^{[1
]}

Hamilton, G. ^{[2
]}

Turic, D. ^{[1
]}

Jehu, L. ^{[1
]}

Harold, D. ^{[1
]}

Abraham, R. ^{[1
]}

Hollingworth, P. ^{[1
]}

Moskvina, V. ^{[3
]}

Brayne, C. ^{[4
]}

Rubinsztein, D. C. ^{[4
]}

Lynch, A. ^{[5
,6
]}

Lawlor, B. ^{[5
,6
]}

Gill, M. ^{[5
,6
]}

O'Donovan, M.

Powell, J. ^{[2
]}

Lovestone, S. ^{[2
]}

Williams, J. ^{[1
,3
]}

Owen, M. J. ^{[1
]}

机构：

[1] Cardiff Univ, Dept Psychol Med, Cardiff CF14 4XN, S Glam, Wales

[2] Kings Coll London, Inst Psychiat, Dept Neurosci, London WC2R 2LS, England

[3] Cardiff Univ, Biostat & Bioinformat Unit, Cardiff CF14 4XN, S Glam, Wales

[4] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England

[5] St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland

[6] Trinity Coll Dublin, Dublin, Ireland

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2008年 / 147B卷 / 06期

基金：

英国医学研究理事会;

关键词：

late-onset Alzheimer's disease; chromosome; 10; SNP; association;

D O I：

10.1002/ajmg.b.30670

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Late-onset Alzheimer's disease (LOAD) is a genetically complex neurodegenerative disorder. Currently, only the epsilon 4 allele of the Apolipoprotein E gene has been identified unequivocally as a genetic susceptibility factor for LOAD. Others remain to be found. In 2002 we observed genome-wide significant evidence of linkage to a region on chromosome 10q11.23-q21.3 [Myers et al. (2002) Am J Med Genet 114:235-244]. Our objective in this study was to test every gene within the maximum LOD-1 linkage region, for association with LOAD. We obtained results for 528 SNPs from 67 genes, with an average density of I SNP every 10 kb within the genes. We demonstrated nominally significant association with LOAD for 4SNPs: rs1881747 near DKK1 (P = 0.011, OR = 1.24), rs2279420 in ANK3 (P = 0.022, OR = 0.79), rs2306402 in CTNNA3 (P = 0.024, OR = 1.18), and rs5030882 in CXXC6 (P=0.046, OR=1.29) in 1,160 cases and 1,389 controls. These results would not survive correction for multiple testing but warrant attempts at confirmation in independent samples. (c) 2007 Wiley-Liss, Inc.

引用

页码：727 / 731

页数：5

共 31 条

[1] PREVALENCE OF DEMENTIA AND PROBABLE SENILE DEMENTIA OF THE ALZHEIMER TYPE IN THE FRAMINGHAM-STUDY [J].

BACHMAN, DL ;

WOLF, PA ;

LINN, R ;

KNOEFEL, JE ;

COBB, J ;

BELANGER, A ;

DAGOSTINO, RB ;

WHITE, LR .

NEUROLOGY, 1992, 42 (01) :115-119

[2] Association testing by DNA pooling: An effective initial screen [J].

Bansal, A ;

van den Boom, D ;

Kammerer, S ;

Honisch, C ;

Adam, G ;

Cantor, CR ;

Kleyn, P ;

Braun, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (26) :16871-16874

[3] Evidence for genetic linkage of Alzheimer's disease to chromosome 10q [J].

Bertram, L ;

Blacker, D ;

Mullin, K ;

Keeney, D ;

Jones, J ;

Basu, S ;

Yhu, S ;

McInnis, MG ;

Go, RCP ;

Vekrellis, K ;

Selkoe, DJ ;

Saunders, AJ ;

Tanzi, RE .

SCIENCE, 2000, 290 (5500) :2302-+

[4] Is α-T catenin (VR22) an Alzheimer's disease risk gene? [J].

Bertram, Lars ;

Mullin, Kristina ;

Parkinson, Michele ;

Hsiao, Monica ;

Moscarillo, Thomas J. ;

Wagner, Steven L. ;

Becker, K. David ;

Velicelebi, Gonul ;

Blacker, Deborah ;

Tanzi, Rudolph E. .

JOURNAL OF MEDICAL GENETICS, 2007, 44 (01)

[5] Results of a high-resolution genome screen of 437 Alzheimer's Disease families [J].

Blacker, D ;

Bertram, L ;

Saunders, AJ ;

Moscarillo, TJ ;

Albert, MS ;

Wiener, H ;

Perry, RT ;

Collins, JS ;

Harrell, LE ;

Go, RCP ;

Mahoney, A ;

Beaty, T ;

Fallin, MD ;

Avramopoulos, D ;

Chase, GA ;

Folstein, MF ;

McInnis, MG ;

Bassett, SS ;

Doheny, KJ ;

Pugh, EW ;

Tanzi, RE .

HUMAN MOLECULAR GENETICS, 2003, 12 (01) :23-32

[6] Genetic variation in CTNNA3 encoding alpha-3 catenin and Alzheimer's disease [J].

Blomqvist, MEL ;

Andreasen, N ;

Bogdanovic, N ;

Blennow, K ;

Brookes, AJ ;

Prince, JA .

NEUROSCIENCE LETTERS, 2004, 358 (03) :220-222

[7] α-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer's disease [J].

Busby, V ;

Goossens, S ;

Nowotny, P ;

Hamilton, G ;

Smemo, S ;

Harold, D ;

Turic, D ;

Jehu, L ;

Myers, A ;

Womick, M ;

Woo, D ;

Compton, D ;

Doil, LM ;

Tacey, KM ;

Lau, KF ;

Al-Saraj, S ;

Killick, R ;

Pickering-Brown, S ;

Moore, P ;

Hollingworth, P ;

Archer, N ;

Foy, C ;

Walter, S ;

Lendon, C ;

Iwatsubo, T ;

Morris, JC ;

Norton, J ;

Mann, D ;

Janssens, B ;

Hardy, J ;

O'Donovan, M ;

Jones, L ;

Williams, J ;

Holmans, P ;

Owen, MJ ;

Grupe, A ;

Powell, J ;

van Hengel, J ;

Goate, A ;

Van Roy, F ;

Lovestone, S .

NEUROMOLECULAR MEDICINE, 2004, 5 (02) :133-146

[8] MUTATIONS OF THE PRESENILIN-I GENE IN FAMILIES WITH EARLY-ONSET ALZHEIMERS-DISEASE [J].

CAMPION, D ;

FLAMAN, JM ;

BRICE, A ;

HANNEQUIN, D ;

DUBOIS, B ;

MARTIN, C ;

MOREAU, V ;

CHARBONNIER, F ;

DIDIERJEAN, O ;

TARDIEU, S ;

PENET, C ;

PUEL, M ;

PASQUIER, F ;

LEDOZE, F ;

BELLIS, G ;

CALENDA, A ;

HEILIG, R ;

MARTINEZ, M ;

MALLET, J ;

BELLIS, M ;

CLERGETDARPOUX, F ;

AGID, Y ;

FREBOURG, T .

HUMAN MOLECULAR GENETICS, 1995, 4 (12) :2373-2377

[9] Insulin degrading enzyme and alpha-3 catenin polymorphisms in Italian patients with Alzheimer disease [J].

Cellini, E ;

Bagnoli, S ;

Tedde, A ;

Nacmias, B ;

Sorbi, S .

ALZHEIMER DISEASE & ASSOCIATED DISORDERS, 2005, 19 (04) :246-247

[10] GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].

CORDER, EH ;

SAUNDERS, AM ;

STRITTMATTER, WJ ;

SCHMECHEL, DE ;

GASKELL, PC ;

SMALL, GW ;

ROSES, AD ;

HAINES, JL ;

PERICAKVANCE, MA .

SCIENCE, 1993, 261 (5123) :921-923

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