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

Institut für Neurogenetik

980 Zitate (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.

Originalsprache	Englisch
Zeitschrift	Nature Genetics
Jahrgang	41
Ausgabenummer	12
Seiten (von - bis)	1308-1312
Seitenumfang	5
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.487
Publikationsstatus	Veröffentlicht - 01.12.2009

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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

@article{98c8498244ab44958ac3a7fd6ec81640,

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",

year = "2009",

month = dec,

day = "1",

doi = "10.1038/ng.487",

language = "English",

volume = "41",

pages = "1308--1312",

journal = "Nature Genetics",

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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, Jg. 41, Nr. 12, S. 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 - http://www.scopus.com/inward/record.url?scp=70549088602&partnerID=8YFLogxK

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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