Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium

被引：28

作者：

Heckman, Michael G. ^{[1
]}

Soto-Ortolaza, Alexandra I. ^{[2
]}

Aasly, Jan O. ^{[3
]}

Abahuni, Nadine ^{[4
]}

Annesi, Grazia ^{[5
]}

Bacon, Justin A. ^{[2
]}

Bardien, Soraya ^{[6
]}

Bozi, Maria ^{[7
]}

Brice, Alexis ^{[8
,9
,10
,11
]}

Brighina, Laura ^{[12
]}

Carr, Jonathan ^{[13
]}

Chartier-Harlin, Marie-Christine ^{[14
,15
]}

Dardiotis, Efthimios ^{[16
,17
]}

Dickson, Dennis W. ^{[2
]}

Diehl, Nancy N. ^{[1
]}

Elbaz, Alexis ^{[18
,19
]}

Ferrarese, Carlo ^{[12
]}

Fiske, Brian ^{[20
]}

Gibson, J. Mark ^{[21
]}

Gibson, Rachel ^{[22
]}

Hadjigeorgiou, Georgios M. ^{[16
,17
]}

Hattori, Nobutaka ^{[23
]}

Ioannidis, John P. A. ^{[24
,25
]}

Boczarska-Jedynak, Magdalena ^{[26
]}

Jasinska-Myga, Barbara ^{[26
]}

Jeon, Beom S. ^{[27
]}

Kim, Yun Joong ^{[28
,29
]}

Klein, Christine ^{[30
]}

Kruger, Rejko ^{[31
,32
]}

Kyratzi, Elli ^{[33
,34
]}

Lesage, Suzanne ^{[8
,9
,10
]}

Lin, Chin-Hsien ^{[35
,36
]}

Lynch, Timothy ^{[37
]}

Maraganore, Demetrius M. ^{[38
]}

Mellick, George D. ^{[39
]}

Mutez, Eugenie ^{[14
,15
,40
]}

Nilsson, Christer ^{[41
]}

Opala, Grzegorz ^{[26
]}

Park, Sung Sup ^{[42
]}

Petrucci, Simona ^{[43
]}

Puschmann, Andreas ^{[44
,45
]}

Quattrone, Aldo ^{[46
,47
]}

Sharma, Manu ^{[31
,32
]}

Silburn, Peter A. ^{[48
]}

Sohn, Young Ho ^{[49
]}

Stefanis, Leonidas ^{[33
,34
]}

Tadic, Vera ^{[30
]}

Theuns, Jessie ^{[50
,51
]}

Tomiyama, Hiroyuki ^{[23
]}

Uitti, Ryan J. ^{[52
]}

机构：

[1] Mayo Clin, Biostat Unit, Jacksonville, FL 32224 USA

[2] Mayo Clin Jacksonville, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA

[3] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway

[4] Goethe Univ Frankfurt, Dept Neurol, D-60054 Frankfurt, Germany

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

[6] Univ Stellenbosch, Div Human Genet & Mol Biol, Cape Town, South Africa

[7] Gen Hosp Syros, Syros, Greece

[8] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Med Res Unit S975, Paris, France

[9] INSERM, U975, Paris, France

[10] CNRS, Med Res Unit 7225, Paris, France

[11] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Paris, France

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

[13] Univ Stellenbosch, Div Neurol, Cape Town, South Africa

[14] Univ Lille Nord France, Ctr Rech Jean Aubert, Lille, France

[15] INSERM, U837, F-59045 Lille, France

[16] Univ Thessaly, Fac Med, Dept Neurol, Neurogenet Lab, Larisa, Greece

[17] Ctr Res & Technol Thessaly, Inst Biomed Res & Technol, Larisa, Greece

[18] INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France

[19] Univ Versailles St Quentin, Med Res Unit 1018, Versailles, France

[20] Michael J Fox Fdn Parkinsons Res, New York, NY USA

[21] Royal Victoria Hosp, Dept Neurol, Belfast, Antrim, Ireland

[22] GlaxoSmithKline Pharmaceut Ltd, Res & Dev, Stevenage, Herts, England

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

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

[25] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA

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

[27] Seoul Natl Univ Hosp, Dept Neurol, Seoul 110744, South Korea

[28] Hallym Univ, ILSONG Inst Life Sci, Anyang, South Korea

[29] Hallym Univ, Dept Neurol, Anyang, South Korea

[30] Med Univ Lubeck, Sect Clin & Mol Neurogenet, Dept Neurol, D-23538 Lubeck, Germany

[31] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany

[32] Univ Tubingen, German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany

[33] Acad Athens, Biomed Res Fdn, Div Basic Neurosci, Athens, Greece

[34] Acad Athens, Biomed Res Fdn, Div Cell Biol, Athens, Greece

[35] Natl Taiwan Univ Hosp, Dept Neurol, Yun Lin Branch, Yunlin, Taiwan

[36] Univ Coll Dublin, Mater Misericordiae Univ Hosp, Dublin Neurol Inst, Dublin 2, Ireland

[37] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 2, Ireland

[38] North Shore Univ Hlth Syst, Dept Neurol, Evanston, IL USA

[39] Griffith Univ, Eskitis Inst Cell & Mol Therapies, Brisbane, Qld 4111, Australia

[40] Ctr Hosp Reg Univ Lille, Lille, France

[41] Lund Univ, Dept Clin Sci, Clin Memory Res Unit, Lund, Sweden

[42] Seoul Natl Univ Hosp, Dept Lab Med, Seoul 110744, South Korea

[43] Sofferenza Hosp, Carattere Sci Casa Sollievo, Ist Ricovero & Cura, Mendel Lab, San Giovanni Rotondo, Italy

[44] Skane Univ Hosp, Dept Neurol, Lund, Sweden

[45] Lund Univ, Dept Neurol, Lund, Sweden

[46] Magna Graecia Univ Catanzaro, Dept Med Sci, Inst Neurol, Catanzaro, Italy

[47] CNR, Neuroimaging Res Unit, Catanzaro, Italy

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

[49] Yonsei Univ, Coll Med, Dept Neurol, Seoul, South Korea

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

来源：

MOVEMENT DISORDERS | 2013年 / 28卷 / 12期

关键词：

Parkinson's disease; LRRK2; genetics; association study; ALPHA-SYNUCLEIN; ASSOCIATION; VPS35; RISK;

D O I：

10.1002/mds.25600

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society

引用

页码：1740 / 1744

页数：5

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