Genome-wide association study reveals genetic risk underlying Parkinson's disease

Javier Simón-Sánchez; Claudia Schulte; Jose M. Bras; Manu Sharma; J. Raphael Gibbs; Daniela Berg; Coro Paisan-Ruiz; Peter Lichtner; Sonja W. Scholz; Dena G. Hernandez; Rejko Krüger; Monica Federoff; Christine Klein; Alison Goate; Joel Perlmutter; Michael Bonin; Michael A. Nalls; Thomas Illig; Christian Gieger; Henry Houlden; Michael Steffens; Michael S. Okun; Brad A. Racette; Mark R. Cookson; Kelly D. Foote; Hubert H. Fernandez; Bryan J. Traynor; Stefan Schreiber; Sampath Arepalli; Ryan Zonozi; Katrina Gwinn; Marcel Van Der Brug; Grisel Lopez; Stephen J. Chanock; Arthur Schatzkin; Yikyung Park; Albert Hollenbeck; Jianjun Gao; Xuemei Huang; Nick W. Wood; Delia Lorenz; Günther Deuschl; Honglei Chen; Olaf Riess; John A. Hardy; Andrew B. Singleton; Thomas Gasser

doi:10.1038/ng.487

Genome-wide association study reveals genetic risk underlying Parkinson's disease

Javier Simón-Sánchez, Claudia Schulte, Jose M. Bras, Manu Sharma, J. Raphael Gibbs, Daniela Berg, Coro Paisan-Ruiz, Peter Lichtner, Sonja W. Scholz, Dena G. Hernandez, Rejko Krüger, Monica Federoff, Christine Klein, Alison Goate, Joel Perlmutter, Michael Bonin, Michael A. Nalls, Thomas Illig, Christian Gieger, Henry HouldenMichael Steffens, Michael S. Okun, Brad A. Racette, Mark R. Cookson, Kelly D. Foote, Hubert H. Fernandez, Bryan J. Traynor, Stefan Schreiber, Sampath Arepalli, Ryan Zonozi, Katrina Gwinn, Marcel Van Der Brug, Grisel Lopez, Stephen J. Chanock, Arthur Schatzkin, Yikyung Park, Albert Hollenbeck, Jianjun Gao, Xuemei Huang, Nick W. Wood, Delia Lorenz, Günther Deuschl, Honglei Chen, Olaf Riess, John A. Hardy, Andrew B. Singleton, Thomas Gasser

Institute of Neurogenetics

1651 Citations (Scopus)

Abstract

We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding α-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 × 10 16) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 × 10 16). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 × 10 8) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 × 10 5). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

Original language	English
Journal	Nature Genetics
Volume	41
Issue number	12
Pages (from-to)	1308-1312
Number of pages	5
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.487
Publication status	Published - 01.12.2009

Funding

We thank the subjects involved in this study whose contribution made this work possible. This work used samples and clinical data from the US National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds). This work was supported in part by the Intramural Research Programs of the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the National Institute of Environmental Health Sciences, the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services; project numbers Z01 AG000949-02 and Z01-ES101986. The KORA research platform (KORA: Cooperative Research in the Region of Augsburg; http://www.gsf.de/KORA) was initiated and financed by the Forschungszentrum für Umwelt und Gesundheit (GSF), which is funded by the German Federal Ministry of Education, Science, Research and Technology and by the State of Bavaria. The study was additionally funded by the German National Genome Network (NGFNplus #01GS08134; German Ministry for Education and Research) and in addition by the German Federal Ministry of Education and Research (BMBF) NGFN (01GR0468). This work also was supported by the National Institutes of Health NINDS P30NS05710 (Neuroscience Blueprint Grant) and Clinical Sciences Translational Award RR024992 to Washington University in St. Louis and the Greater St. Louis Chapter of the American Parkinson Disease Association. Authors received support from the Medical Research Council, UK.

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Simón-Sánchez, J., Schulte, C., Bras, J. M., Sharma, M., Gibbs, J. R., Berg, D., Paisan-Ruiz, C., Lichtner, P., Scholz, S. W., Hernandez, D. G., Krüger, R., Federoff, M., Klein, C., Goate, A., Perlmutter, J., Bonin, M., Nalls, M. A., Illig, T., Gieger, C., ... Gasser, T. (2009). Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nature Genetics, 41(12), 1308-1312. https://doi.org/10.1038/ng.487

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title = "Genome-wide association study reveals genetic risk underlying Parkinson's disease",

abstract = "We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding α-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 × 10 16) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 × 10 16). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 × 10 8) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 × 10 5). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.",

author = "Javier Sim{\'o}n-S{\'a}nchez and Claudia Schulte and Bras, \{Jose M.\} and Manu Sharma and Gibbs, \{J. Raphael\} and Daniela Berg and Coro Paisan-Ruiz and Peter Lichtner and Scholz, \{Sonja W.\} and Hernandez, \{Dena G.\} and Rejko Kr{\"u}ger and Monica Federoff and Christine Klein and Alison Goate and Joel Perlmutter and Michael Bonin and Nalls, \{Michael A.\} and Thomas Illig and Christian Gieger and Henry Houlden and Michael Steffens and Okun, \{Michael S.\} and Racette, \{Brad A.\} and Cookson, \{Mark R.\} and Foote, \{Kelly D.\} and Fernandez, \{Hubert H.\} and Traynor, \{Bryan J.\} and Stefan Schreiber and Sampath Arepalli and Ryan Zonozi and Katrina Gwinn and \{Van Der Brug\}, Marcel and Grisel Lopez and Chanock, \{Stephen J.\} and Arthur Schatzkin and Yikyung Park and Albert Hollenbeck and Jianjun Gao and Xuemei Huang and Wood, \{Nick W.\} and Delia Lorenz and G{\"u}nther Deuschl and Honglei Chen and Olaf Riess and Hardy, \{John A.\} and Singleton, \{Andrew B.\} and Thomas Gasser",

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Simón-Sánchez, J, Schulte, C, Bras, JM, Sharma, M, Gibbs, JR, Berg, D, Paisan-Ruiz, C, Lichtner, P, Scholz, SW, Hernandez, DG, Krüger, R, Federoff, M, Klein, C, Goate, A, Perlmutter, J, Bonin, M, Nalls, MA, Illig, T, Gieger, C, Houlden, H, Steffens, M, Okun, MS, Racette, BA, Cookson, MR, Foote, KD, Fernandez, HH, Traynor, BJ, Schreiber, S, Arepalli, S, Zonozi, R, Gwinn, K, Van Der Brug, M, Lopez, G, Chanock, SJ, Schatzkin, A, Park, Y, Hollenbeck, A, Gao, J, Huang, X, Wood, NW, Lorenz, D, Deuschl, G, Chen, H, Riess, O, Hardy, JA, Singleton, AB & Gasser, T 2009, 'Genome-wide association study reveals genetic risk underlying Parkinson's disease', Nature Genetics, vol. 41, no. 12, pp. 1308-1312. https://doi.org/10.1038/ng.487

TY - JOUR

T1 - Genome-wide association study reveals genetic risk underlying Parkinson's disease

AU - Simón-Sánchez, Javier

AU - Schulte, Claudia

AU - Bras, Jose M.

AU - Sharma, Manu

AU - Gibbs, J. Raphael

AU - Berg, Daniela

AU - Paisan-Ruiz, Coro

AU - Lichtner, Peter

AU - Scholz, Sonja W.

AU - Hernandez, Dena G.

AU - Krüger, Rejko

AU - Federoff, Monica

AU - Klein, Christine

AU - Goate, Alison

AU - Perlmutter, Joel

AU - Bonin, Michael

AU - Nalls, Michael A.

AU - Illig, Thomas

AU - Gieger, Christian

AU - Houlden, Henry

AU - Steffens, Michael

AU - Okun, Michael S.

AU - Racette, Brad A.

AU - Cookson, Mark R.

AU - Foote, Kelly D.

AU - Fernandez, Hubert H.

AU - Traynor, Bryan J.

AU - Schreiber, Stefan

AU - Arepalli, Sampath

AU - Zonozi, Ryan

AU - Gwinn, Katrina

AU - Van Der Brug, Marcel

AU - Lopez, Grisel

AU - Chanock, Stephen J.

AU - Schatzkin, Arthur

AU - Park, Yikyung

AU - Hollenbeck, Albert

AU - Gao, Jianjun

AU - Huang, Xuemei

AU - Wood, Nick W.

AU - Lorenz, Delia

AU - Deuschl, Günther

AU - Chen, Honglei

AU - Riess, Olaf

AU - Hardy, John A.

AU - Singleton, Andrew B.

AU - Gasser, Thomas

PY - 2009/12/1

Y1 - 2009/12/1

N2 - We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding α-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 × 10 16) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 × 10 16). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 × 10 8) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 × 10 5). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

AB - We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding α-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 × 10 16) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 × 10 16). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 × 10 8) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 × 10 5). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

UR - https://www.scopus.com/pages/publications/70549088602

U2 - 10.1038/ng.487

DO - 10.1038/ng.487

M3 - Journal articles

C2 - 19915575

AN - SCOPUS:70549088602

SN - 1061-4036

VL - 41

SP - 1308

EP - 1312

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Genome-wide association study reveals genetic risk underlying Parkinson's disease

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