Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium

Michael G. Heckman, Alexandra I. Soto-Ortolaza, Jan O. Aasly, Nadine Abahuni, Grazia Annesi, Justin A. Bacon, Soraya Bardien, Maria Bozi, Alexis Brice, Laura Brighina, Jonathan Carr, Marie Christine Chartier-Harlin, Efthimios Dardiotis, Dennis W Dickson, Nancy N. Diehl, Alexis Elbaz, Carlo Ferrarese, Brian Fiske, J. Mark Gibson, Rachel GibsonGeorgios M. Hadjigeorgiou, Nobutaka Hattori, John P A Ioannidis, Magdalena Boczarska-Jedynak, Barbara Jasinska-Myga, Beom S. Jeon, Yun Joong Kim, Christine Klein, Rejko Kruger, Elli Kyratzi, Suzanne Lesage, Chin Hsien Lin, Timothy Lynch, Demetrius M. Maraganore, George D. Mellick, Eugénie Mutez, Christer Nilsson, Grzegorz Opala, Sung Sup Park, Simona Petrucci, Andreas Puschmann, Aldo Quattrone, Manu Sharma, Peter A. Silburn, Young Ho Sohn, Leonidas Stefanis, Vera Tadic, Jessie Theuns, Hiroyuki Tomiyama, Ryan J. Uitti, Enza Maria Valente, Christine Van Broeckhoven, Simone Van De Loo, Demetrios K. Vassilatis, Carles Vilariño-Güell, Linda R. White, Karin Wirdefeldt, Zbigniew K Wszolek, Ruey Meei Wu, Faycal Hentati, Matthew J. Farrer, Owen A Ross

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Variants 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. Methods: The 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. Results: Herein, 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. Conclusions: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.

Original languageEnglish (US)
Pages (from-to)1740-1744
Number of pages5
JournalMovement Disorders
Volume28
Issue number12
DOIs
StatePublished - Oct 2013

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Molecular Epidemiology
Leucine
Parkinson Disease
Phosphotransferases
Gene Frequency
Population
Disease Susceptibility
Genetic Association Studies
Haplotypes
Genes
Publications
Therapeutics

Keywords

  • Association study
  • Genetics
  • LRRK2
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium. / Heckman, Michael G.; Soto-Ortolaza, Alexandra I.; Aasly, Jan O.; Abahuni, Nadine; Annesi, Grazia; Bacon, Justin A.; Bardien, Soraya; Bozi, Maria; Brice, Alexis; Brighina, Laura; Carr, Jonathan; Chartier-Harlin, Marie Christine; Dardiotis, Efthimios; Dickson, Dennis W; Diehl, Nancy N.; Elbaz, Alexis; Ferrarese, Carlo; Fiske, Brian; Gibson, J. Mark; Gibson, Rachel; Hadjigeorgiou, Georgios M.; Hattori, Nobutaka; Ioannidis, John P A; Boczarska-Jedynak, Magdalena; Jasinska-Myga, Barbara; Jeon, Beom S.; Kim, Yun Joong; Klein, Christine; Kruger, Rejko; Kyratzi, Elli; Lesage, Suzanne; Lin, Chin Hsien; Lynch, Timothy; Maraganore, Demetrius M.; Mellick, George D.; Mutez, Eugénie; Nilsson, Christer; Opala, Grzegorz; Park, Sung Sup; Petrucci, Simona; Puschmann, Andreas; Quattrone, Aldo; Sharma, Manu; Silburn, Peter A.; Sohn, Young Ho; Stefanis, Leonidas; Tadic, Vera; Theuns, Jessie; Tomiyama, Hiroyuki; Uitti, Ryan J.; Valente, Enza Maria; Van Broeckhoven, Christine; Van De Loo, Simone; Vassilatis, Demetrios K.; Vilariño-Güell, Carles; White, Linda R.; Wirdefeldt, Karin; Wszolek, Zbigniew K; Wu, Ruey Meei; Hentati, Faycal; Farrer, Matthew J.; Ross, Owen A.

In: Movement Disorders, Vol. 28, No. 12, 10.2013, p. 1740-1744.

Research output: Contribution to journalArticle

Heckman, MG, Soto-Ortolaza, AI, Aasly, JO, Abahuni, N, Annesi, G, Bacon, JA, Bardien, S, Bozi, M, Brice, A, Brighina, L, Carr, J, Chartier-Harlin, MC, Dardiotis, E, Dickson, DW, Diehl, NN, Elbaz, A, Ferrarese, C, Fiske, B, Gibson, JM, Gibson, R, Hadjigeorgiou, GM, Hattori, N, Ioannidis, JPA, Boczarska-Jedynak, M, Jasinska-Myga, B, Jeon, BS, Kim, YJ, Klein, C, Kruger, R, Kyratzi, E, Lesage, S, Lin, CH, Lynch, T, Maraganore, DM, Mellick, GD, Mutez, E, Nilsson, C, Opala, G, Park, SS, Petrucci, S, Puschmann, A, Quattrone, A, Sharma, M, Silburn, PA, Sohn, YH, Stefanis, L, Tadic, V, Theuns, J, Tomiyama, H, Uitti, RJ, Valente, EM, Van Broeckhoven, C, Van De Loo, S, Vassilatis, DK, Vilariño-Güell, C, White, LR, Wirdefeldt, K, Wszolek, ZK, Wu, RM, Hentati, F, Farrer, MJ & Ross, OA 2013, 'Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium', Movement Disorders, vol. 28, no. 12, pp. 1740-1744. https://doi.org/10.1002/mds.25600
Heckman, Michael G. ; Soto-Ortolaza, Alexandra I. ; Aasly, Jan O. ; Abahuni, Nadine ; Annesi, Grazia ; Bacon, Justin A. ; Bardien, Soraya ; Bozi, Maria ; Brice, Alexis ; Brighina, Laura ; Carr, Jonathan ; Chartier-Harlin, Marie Christine ; Dardiotis, Efthimios ; Dickson, Dennis W ; Diehl, Nancy N. ; Elbaz, Alexis ; Ferrarese, Carlo ; Fiske, Brian ; Gibson, J. Mark ; Gibson, Rachel ; Hadjigeorgiou, Georgios M. ; Hattori, Nobutaka ; Ioannidis, John P A ; Boczarska-Jedynak, Magdalena ; Jasinska-Myga, Barbara ; Jeon, Beom S. ; Kim, Yun Joong ; Klein, Christine ; Kruger, Rejko ; Kyratzi, Elli ; Lesage, Suzanne ; Lin, Chin Hsien ; Lynch, Timothy ; Maraganore, Demetrius M. ; Mellick, George D. ; Mutez, Eugénie ; Nilsson, Christer ; Opala, Grzegorz ; Park, Sung Sup ; Petrucci, Simona ; Puschmann, Andreas ; Quattrone, Aldo ; Sharma, Manu ; Silburn, Peter A. ; Sohn, Young Ho ; Stefanis, Leonidas ; Tadic, Vera ; Theuns, Jessie ; Tomiyama, Hiroyuki ; Uitti, Ryan J. ; Valente, Enza Maria ; Van Broeckhoven, Christine ; Van De Loo, Simone ; Vassilatis, Demetrios K. ; Vilariño-Güell, Carles ; White, Linda R. ; Wirdefeldt, Karin ; Wszolek, Zbigniew K ; Wu, Ruey Meei ; Hentati, Faycal ; Farrer, Matthew J. ; Ross, Owen A. / Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium. In: Movement Disorders. 2013 ; Vol. 28, No. 12. pp. 1740-1744.
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abstract = "Background: Variants 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. Methods: The 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. Results: Herein, 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. Conclusions: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.",
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T1 - Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium

AU - Heckman, Michael G.

AU - Soto-Ortolaza, Alexandra I.

AU - Aasly, Jan O.

AU - Abahuni, Nadine

AU - Annesi, Grazia

AU - Bacon, Justin A.

AU - Bardien, Soraya

AU - Bozi, Maria

AU - Brice, Alexis

AU - Brighina, Laura

AU - Carr, Jonathan

AU - Chartier-Harlin, Marie Christine

AU - Dardiotis, Efthimios

AU - Dickson, Dennis W

AU - Diehl, Nancy N.

AU - Elbaz, Alexis

AU - Ferrarese, Carlo

AU - Fiske, Brian

AU - Gibson, J. Mark

AU - Gibson, Rachel

AU - Hadjigeorgiou, Georgios M.

AU - Hattori, Nobutaka

AU - Ioannidis, John P A

AU - Boczarska-Jedynak, Magdalena

AU - Jasinska-Myga, Barbara

AU - Jeon, Beom S.

AU - Kim, Yun Joong

AU - Klein, Christine

AU - Kruger, Rejko

AU - Kyratzi, Elli

AU - Lesage, Suzanne

AU - Lin, Chin Hsien

AU - Lynch, Timothy

AU - Maraganore, Demetrius M.

AU - Mellick, George D.

AU - Mutez, Eugénie

AU - Nilsson, Christer

AU - Opala, Grzegorz

AU - Park, Sung Sup

AU - Petrucci, Simona

AU - Puschmann, Andreas

AU - Quattrone, Aldo

AU - Sharma, Manu

AU - Silburn, Peter A.

AU - Sohn, Young Ho

AU - Stefanis, Leonidas

AU - Tadic, Vera

AU - Theuns, Jessie

AU - Tomiyama, Hiroyuki

AU - Uitti, Ryan J.

AU - Valente, Enza Maria

AU - Van Broeckhoven, Christine

AU - Van De Loo, Simone

AU - Vassilatis, Demetrios K.

AU - Vilariño-Güell, Carles

AU - White, Linda R.

AU - Wirdefeldt, Karin

AU - Wszolek, Zbigniew K

AU - Wu, Ruey Meei

AU - Hentati, Faycal

AU - Farrer, Matthew J.

AU - Ross, Owen A

PY - 2013/10

Y1 - 2013/10

N2 - Background: Variants 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. Methods: The 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. Results: Herein, 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. Conclusions: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.

AB - Background: Variants 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. Methods: The 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. Results: Herein, 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. Conclusions: Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.

KW - Association study

KW - Genetics

KW - LRRK2

KW - Parkinson's disease

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