A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease

被引：46

作者：

Krueger, Rejko ^{[1
,2
]}

Sharma, Manu ^{[1
,2
]}

Riess, Olaf

Gasser, Thomas ^{[1
,2
]}

Van Broeckhoven, Christine ^{[3
]}

Theuns, Jessie ^{[3
]}

Aasly, Jan ^{[4
]}

Annesi, Grazia ^{[5
]}

Bentivoglio, Anna Rita ^{[6
]}

Brice, Alexis ^{[7
,8
,9
]}

Djarmati, Ana ^{[10
]}

Elbaz, Alexis ^{[11
,12
]}

Farrer, Matthew ^{[13
]}

Ferrarese, Carlo ^{[14
]}

Gibson, J. Mark ^{[15
,16
,17
]}

Hadjigeorgiou, Georgios M. ^{[18
,19
]}

Hattori, Nobutaka ^{[20
]}

Ioannidis, John P. A. ^{[21
]}

Jasinska-Myga, Barbara ^{[22
]}

Klein, Christine ^{[10
]}

Lambert, Jean-Charles ^{[33
]}

Lesage, Suzanne ^{[7
,8
,9
]}

Lin, Juei-Jueng

Lynch, Timothy ^{[15
,16
,17
]}

Mellick, George D. ^{[23
,24
]}

de Nigris, Francesa ^{[6
]}

Opala, Grzegorz ^{[22
]}

Prigione, Alessandro ^{[14
]}

Quattrone, Aldo ^{[25
]}

Ross, Owen A. ^{[13
]}

Satake, Wataru ^{[26
]}

Silburn, Peter A. ^{[23
,24
]}

Tan, Eng King ^{[27
,28
]}

Toda, Tatsushi ^{[26
]}

Tomiyama, Hiroyuki ^{[20
,21
]}

Wirdefeldt, Karin ^{[29
,30
]}

Wszolek, Zbigniew ^{[31
]}

Xiromerisiou, Georgia ^{[18
,19
]}

Maraganore, Demetrius M. ^{[32
]}

机构：

[1] Univ Tubingen, Ctr Neurol, Lab Funct Neurogenom, D-72076 Tubingen, Germany

[2] Univ Tubingen, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany

[3] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium

[4] Univ Trondheim, Dept Neurol, N-7034 Trondheim, Norway

[5] CNR, Inst Neurol Sci, Cosenza, Italy

[6] Univ Cattolica Sacro Cuore, Dept Neurol, Rome, Italy

[7] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France

[8] INSERM, U975, Paris, France

[9] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, F-75013 Paris, France

[10] Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, Lubeck, Germany

[11] Univ Paris 06, INSERM, U708, F-75013 Paris, France

[12] Univ Paris 06, U708, F-75005 Paris, France

[13] Mayo Clin, Dept Genet, Jacksonville, FL USA

[14] Univ Milano Bicocca, San Gerardo Hosp, Neurol Sect, Dept Neurosci, Monza, Italy

[15] Univ Coll Dublin, Conway Inst, Dublin, Ireland

[16] Mater Misericordiae Univ Hosp, Dublin Neurol Inst, Dublin, Ireland

[17] Royal Victoria Hosp, Dept Neurol, Belfast BT12 6BA, Antrim, North Ireland

[18] Univ Thessaly, Sch Med, Neurogenet Lab, Dept Neurol, Larisa, Greece

[19] CERETETH, Inst Biomed Res & Technol, Larisa, Greece

[20] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan

[21] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece

[22] Med Univ Silesia, Dept Neurol, Katowice, Poland

[23] Griffith Univ, Sch Biomol & Phys Sci, Eskitis Inst Cell & Mol Therapies, Nathan, Qld 4111, Australia

[24] Univ Queensland, Clin Res Ctr, Royal Brisbane Hosp, Brisbane, Qld 4072, Australia

[25] Magna Graecia Univ Catanzaro, Inst Neurol, Catanzaro, Italy

[26] Kobe Univ, Grad Sch Med, Div Neurol Mol Brain Sci, Kobe, Hyogo, Japan

[27] Singapore Gen Hosp, Natl Inst Neurosci, Dept Neurol, Singapore 0316, Singapore

[28] Duke NUS Grad Med Sch, Singapore, Singapore

[29] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[30] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden

[31] Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL USA

[32] Mayo Clin, Dept Neurol, Rochester, MN USA

[33] Univ Lille 2, Inst Pasteur Lille, INSERM, U744, Lille, France

来源：

NEUROBIOLOGY OF AGING | 2011年 / 32卷 / 03期

关键词：

Omi; HtrA2; Genetics; Parkinson's disease; PARK13; EARLY-ONSET PARKINSONISM; GENOME-WIDE ASSOCIATION; MUTATIONS; VARIABILITY; UNCERTAINTY;

D O I：

10.1016/j.neurobiolaging.2009.11.021

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

High-profile studies have provided conflicting results regarding the involvement of the Omi/HtrA2 gene in Parkinson's disease (PD) susceptibility. Therefore, we performed a large-scale analysis of the association of common Omi/HtrA2 variants in the Genetic Epidemiology of Parkinson's disease (GEO-PD) consortium. GEO-PD sites provided clinical and genetic data including affection status, gender, ethnicity, age at study, age at examination (all subjects); age at onset and family history of PD (patients). Genotyping was performed for the five most informative SNPs spanning the Omi/HtrA2 gene in approximately 2-3 kb intervals (rs10779958, rs2231250, rs72470544, rs1183739, rs2241028). Fixed as well as random effect models were used to provide summary risk estimates of Omi/HtrA2 variants. The 20 GEO-PD sites provided data for 6378 cases and 8880 controls. No overall significant associations for the five Omi/HtrA2 SNPs and PD were observed using either fixed effect or random effect models. The summary odds ratios ranged between 0.98 and 1.08 and the estimates of between-study heterogeneity were not large (non-significant Q statistics for all 5 SNPs; I(2) estimates 0-28%). Trends for association were seen for participants of Scandinavian descent for rs2241028 (OR1.41, p = 0.04) and for rs1183739 for age at examination (cut-off 65 years; OR 1.17, p = 0.02), but these would not be significant after adjusting for multiple comparisons and their Bayes factors were only modest. This largest association study performed to define the role of any gene in the pathogenesis of Parkinson's disease revealed no overall strong association of Omi/HtrA2 variants with PD in populations worldwide. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：548.e9 / 548.e18

页数：10

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