Common variation in the LRRK2 gene is a risk factor for Parkinson's disease

Ignacio F. Mata; Harvey Checkoway; Carolyn M. Hutter; Ali Samii; John W. Roberts; Hojoong M. Kim; Pinky Agarwal; Victoria Alvarez; Renee Ribacoba; Pau Pastor; Oswaldo Lorenzo-Betancor; Jon Infante; María Sierra; Pilar Gómez-Garre; Pablo Mir; Beate Ritz; Shannon L. Rhodes; Amy Colcher; Vivianna Van Deerlin; Kathryn A. Chung; Joseph F. Quinn; Dora Yearout; Erica Martinez; Federico M. Farin; Jia Y. Wan; Karen L. Edwards; Cyrus P. Zabetian

doi:10.1002/mds.25226

Common variation in the LRRK2 gene is a risk factor for Parkinson's disease

Ignacio F. Mata, Harvey Checkoway, Carolyn M. Hutter, Ali Samii, John W. Roberts, Hojoong M. Kim, Pinky Agarwal, Victoria Alvarez, Renee Ribacoba, Pau Pastor, Oswaldo Lorenzo-Betancor, Jon Infante, María Sierra, Pilar Gómez-Garre, Pablo Mir, Beate Ritz, Shannon L. Rhodes, Amy Colcher, Vivianna Van Deerlin, Kathryn A. ChungJoseph F. Quinn, Dora Yearout, Erica Martinez, Federico M. Farin, Jia Y. Wan, Karen L. Edwards, Cyrus P. Zabetian

Neurology

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. Methods: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P <.05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. Results: Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10^-4; rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10^-4). Conclusions: Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry.

Original language	English (US)
Pages (from-to)	1823-1826
Number of pages	4
Journal	Movement Disorders
Volume	27
Issue number	14
DOIs	https://doi.org/10.1002/mds.25226
State	Published - Dec 2012

Keywords

LRRK2
Parkinson's disease
SNP

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.25226

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Mata, I. F., Checkoway, H., Hutter, C. M., Samii, A., Roberts, J. W., Kim, H. M., Agarwal, P., Alvarez, V., Ribacoba, R., Pastor, P., Lorenzo-Betancor, O., Infante, J., Sierra, M., Gómez-Garre, P., Mir, P., Ritz, B., Rhodes, S. L., Colcher, A., Van Deerlin, V., ... Zabetian, C. P. (2012). Common variation in the LRRK2 gene is a risk factor for Parkinson's disease. Movement Disorders, 27(14), 1823-1826. https://doi.org/10.1002/mds.25226

Mata, IF, Checkoway, H, Hutter, CM, Samii, A, Roberts, JW, Kim, HM, Agarwal, P, Alvarez, V, Ribacoba, R, Pastor, P, Lorenzo-Betancor, O, Infante, J, Sierra, M, Gómez-Garre, P, Mir, P, Ritz, B, Rhodes, SL, Colcher, A, Van Deerlin, V, Chung, KA , Quinn, JF, Yearout, D, Martinez, E, Farin, FM, Wan, JY, Edwards, KL & Zabetian, CP 2012, 'Common variation in the LRRK2 gene is a risk factor for Parkinson's disease', Movement Disorders, vol. 27, no. 14, pp. 1823-1826. https://doi.org/10.1002/mds.25226

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title = "Common variation in the LRRK2 gene is a risk factor for Parkinson's disease",

abstract = "Background: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. Methods: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P <.05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. Results: Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10-4; rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10-4). Conclusions: Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry.",

keywords = "LRRK2, Parkinson's disease, SNP",

author = "Mata, {Ignacio F.} and Harvey Checkoway and Hutter, {Carolyn M.} and Ali Samii and Roberts, {John W.} and Kim, {Hojoong M.} and Pinky Agarwal and Victoria Alvarez and Renee Ribacoba and Pau Pastor and Oswaldo Lorenzo-Betancor and Jon Infante and Mar{\'i}a Sierra and Pilar G{\'o}mez-Garre and Pablo Mir and Beate Ritz and Rhodes, {Shannon L.} and Amy Colcher and {Van Deerlin}, Vivianna and Chung, {Kathryn A.} and Quinn, {Joseph F.} and Dora Yearout and Erica Martinez and Farin, {Federico M.} and Wan, {Jia Y.} and Edwards, {Karen L.} and Zabetian, {Cyrus P.}",

year = "2012",

month = dec,

doi = "10.1002/mds.25226",

language = "English (US)",

volume = "27",

pages = "1823--1826",

journal = "Movement Disorders",

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T1 - Common variation in the LRRK2 gene is a risk factor for Parkinson's disease

AU - Mata, Ignacio F.

AU - Checkoway, Harvey

AU - Hutter, Carolyn M.

AU - Samii, Ali

AU - Roberts, John W.

AU - Kim, Hojoong M.

AU - Agarwal, Pinky

AU - Alvarez, Victoria

AU - Ribacoba, Renee

AU - Pastor, Pau

AU - Lorenzo-Betancor, Oswaldo

AU - Infante, Jon

AU - Sierra, María

AU - Gómez-Garre, Pilar

AU - Mir, Pablo

AU - Ritz, Beate

AU - Rhodes, Shannon L.

AU - Colcher, Amy

AU - Van Deerlin, Vivianna

AU - Chung, Kathryn A.

AU - Quinn, Joseph F.

AU - Yearout, Dora

AU - Martinez, Erica

AU - Farin, Federico M.

AU - Wan, Jia Y.

AU - Edwards, Karen L.

AU - Zabetian, Cyrus P.

PY - 2012/12

Y1 - 2012/12

N2 - Background: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. Methods: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P <.05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. Results: Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10-4; rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10-4). Conclusions: Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry.

AB - Background: Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. Methods: We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P <.05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. Results: Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10-4; rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10-4). Conclusions: Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry.

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KW - Parkinson's disease

KW - SNP

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EP - 1826

JO - Movement Disorders

JF - Movement Disorders

IS - 14

ER -

Common variation in the LRRK2 gene is a risk factor for Parkinson's disease

Abstract

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