Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease

被引：239

作者：

Carrasquillo, Minerva M. ^{[1
]}

Zou, Fanggeng ^{[1
]}

Pankratz, V. Shane ^{[2
]}

Wilcox, Samantha L. ^{[1
]}

Ma, Li ^{[1
]}

Walker, Louise P. ^{[1
]}

Younkin, Samuel G. ^{[1
]}

Younkin, Curtis S. ^{[1
]}

Younkin, Linda H. ^{[1
]}

Bisceglio, Gina D. ^{[1
]}

Ertekin-Taner, Nilufer ^{[1
,3
]}

Crook, Julia E. ^{[4
]}

Dickson, Dennis W. ^{[1
]}

Petersen, Ronald C. ^{[3
,5
]}

Graff-Radford, Neill R. ^{[1
,3
]}

Younkin, Steven G. ^{[1
]}

机构：

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

[2] Mayo Clin & Mayo Fdn, Div Biomed Stat & Informat, Rochester, MN 55905 USA

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

[4] Mayo Clin, Coll Med, Biostat Unit, Rochester, MN 55905 USA

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

来源：

NATURE GENETICS | 2009年 / 41卷 / 02期

基金：

美国国家卫生研究院;

关键词：

EXPRESSION; POPULATION; CANDIDATE; ALLELE; BRAIN;

D O I：

10.1038/ng.305

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

By analyzing late-onset Alzheimer's disease (LOAD) in a genome-wide association study (313,504 SNPs, three series, 844 cases and 1,255 controls) and evaluating the 25 SNPs with the most significant allelic association in four additional series (1,547 cases and 1,209 controls), we identified a SNP (rs5984894) on Xq21.3 in PCDH11X that is strongly associated with LOAD in individuals of European descent from the United States. Analysis of rs5984894 by multivariable logistic regression adjusted for sex gave global P values of 5.7 x 10(-5) in stage 1, 4.8 x 10(-6) in stage 2 and 3.9 x 10(-12) in the combined data. Odds ratios were 1.75 (95% CI 1.42-2.16) for female homozygotes (P = 2.0 x 10(-7)) and 1.26 (95% CI = 1.05-1.51) for female heterozygotes (P = 0.01) compared to female non-carriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99-1.41).

引用

页码：192 / 198

页数：7

共 15 条

[1] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[2] Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in brain [J].

Blanco, P ;

Sargent, CA ;

Boucher, CA ;

Mitchell, M ;

Affara, NA .

MAMMALIAN GENOME, 2000, 11 (10) :906-914

[3] Protocadherin X (PCDHX) and Y (PCDHY) genes;: multiple mRNA isoforms encoding variant signal peptides and cytoplasmic domains [J].

Blanco-Arias, P ;

Sargent, CA ;

Affara, NA .

MAMMALIAN GENOME, 2004, 15 (01) :41-52

[4] PROTECTIVE EFFECT OF APOLIPOPROTEIN-E TYPE-2 ALLELE FOR LATE-ONSET ALZHEIMER-DISEASE [J].

CORDER, EH ;

SAUNDERS, AM ;

RISCH, NJ ;

STRITTMATTER, WJ ;

SCHMECHEL, DE ;

GASKELL, PC ;

RIMMLER, JB ;

LOCKE, PA ;

CONNEALLY, PM ;

SCHMADER, KE ;

SMALL, GW ;

ROSES, AD ;

HAINES, JL ;

PERICAKVANCE, MA .

NATURE GENETICS, 1994, 7 (02) :180-184

[5] 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

[6] Expression and genetic variability of PCDH11Y, a gene specific to Homo sapiens and candidate for susceptibility to psychiatric disorders [J].

Durand, CM ;

Kappeler, C ;

Betancur, C ;

Delorme, R ;

Quach, H ;

Goubran-Botros, H ;

Melke, J ;

Nygren, G ;

Chabane, N ;

Bellivier, F ;

Szoke, A ;

Schurhoff, F ;

Rastam, M ;

Anckarsäter, H ;

Gillberg, C ;

Leboyer, M ;

Bourgeron, T .

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2006, 141B (01) :67-70

[7] PREVALENCE OF ALZHEIMERS-DISEASE IN A COMMUNITY POPULATION OF OLDER PERSONS - HIGHER THAN PREVIOUSLY REPORTED [J].

EVANS, DA ;

FUNKENSTEIN, H ;

ALBERT, MS ;

SCHERR, PA ;

COOK, NR ;

CHOWN, MJ ;

HEBERT, LE ;

HENNEKENS, CH ;

TAYLOR, JO .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1989, 262 (18) :2551-2556

[8] Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease - A meta-analysis [J].

Farrer, LA ;

Cupples, LA ;

Haines, JL ;

Hyman, B ;

Kukull, WA ;

Mayeux, R ;

Myers, RH ;

PericakVance, MA ;

Risch, N ;

vanDuijn, CM .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 278 (16) :1349-1356

[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] Presenilin-dependent processing and nuclear function of γ-protocadherins [J].

Haas, IG ;

Frank, M ;

Véron, N ;

Kemler, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (10) :9313-9319

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