Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry

for the Michael J. Fox LRRK2 Cohort Consortium

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%-100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80. Methods: The kin-cohort method was used to estimate penetrance in 474 first-degree relatives of 69 non-Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available. Results: Risk of PD in non-Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5% (95% confidence interval [CI]: 26.3%-65.8%) to age 80, which is not significantly higher than the previously estimated 25% (95% CI: 16.7%-34.2%) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives. Conclusions: The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non-Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25% to 42.5% at age 80 in all populations analyzed.

Original languageEnglish (US)
Pages (from-to)1432-1438
Number of pages7
JournalMovement Disorders
Volume32
Issue number10
DOIs
StatePublished - Oct 1 2017

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Penetrance
Leucine
Phosphotransferases
Mutation
Jews
Ethnic Groups
Confidence Intervals
Neurologic Examination
Age of Onset
Genotype
Interviews

Keywords

  • LRRK2
  • Parkinson's disease
  • penetrance

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry. / for the Michael J. Fox LRRK2 Cohort Consortium.

In: Movement Disorders, Vol. 32, No. 10, 01.10.2017, p. 1432-1438.

Research output: Contribution to journalArticle

for the Michael J. Fox LRRK2 Cohort Consortium. / Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry. In: Movement Disorders. 2017 ; Vol. 32, No. 10. pp. 1432-1438.
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title = "Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry",
abstract = "Background: Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24{\%}-100{\%}). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25{\%}, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80. Methods: The kin-cohort method was used to estimate penetrance in 474 first-degree relatives of 69 non-Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available. Results: Risk of PD in non-Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5{\%} (95{\%} confidence interval [CI]: 26.3{\%}-65.8{\%}) to age 80, which is not significantly higher than the previously estimated 25{\%} (95{\%} CI: 16.7{\%}-34.2{\%}) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives. Conclusions: The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non-Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25{\%} to 42.5{\%} at age 80 in all populations analyzed.",
keywords = "LRRK2, Parkinson's disease, penetrance",
author = "{for the Michael J. Fox LRRK2 Cohort Consortium} and Lee, {Annie J.} and Yuanjia Wang and Alcalay, {Roy N.} and Helen Mejia-Santana and Rachel Saunders-Pullman and Susan Bressman and Corvol, {Jean Christophe} and Alexis Brice and Suzanne Lesage and Graziella Mangone and Eduardo Tolosa and Claustre Pont-Sunyer and Dolores Vilas and Birgitt Sch{\"u}le and Farah Kausar and Tatiana Foroud and Daniela Berg and Kathrin Brockmann and Stefano Goldwurm and Chiara Siri and Rosanna Asselta and Javier Ruiz-Martinez and Elisabet Mondrag{\'o}n and Connie Marras and Taneera Ghate and Nir Giladi and Anat Mirelman and Karen Marder",
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T1 - Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non-Ashkenazi Jewish ancestry

AU - for the Michael J. Fox LRRK2 Cohort Consortium

AU - Lee, Annie J.

AU - Wang, Yuanjia

AU - Alcalay, Roy N.

AU - Mejia-Santana, Helen

AU - Saunders-Pullman, Rachel

AU - Bressman, Susan

AU - Corvol, Jean Christophe

AU - Brice, Alexis

AU - Lesage, Suzanne

AU - Mangone, Graziella

AU - Tolosa, Eduardo

AU - Pont-Sunyer, Claustre

AU - Vilas, Dolores

AU - Schüle, Birgitt

AU - Kausar, Farah

AU - Foroud, Tatiana

AU - Berg, Daniela

AU - Brockmann, Kathrin

AU - Goldwurm, Stefano

AU - Siri, Chiara

AU - Asselta, Rosanna

AU - Ruiz-Martinez, Javier

AU - Mondragón, Elisabet

AU - Marras, Connie

AU - Ghate, Taneera

AU - Giladi, Nir

AU - Mirelman, Anat

AU - Marder, Karen

PY - 2017/10/1

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N2 - Background: Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%-100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80. Methods: The kin-cohort method was used to estimate penetrance in 474 first-degree relatives of 69 non-Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available. Results: Risk of PD in non-Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5% (95% confidence interval [CI]: 26.3%-65.8%) to age 80, which is not significantly higher than the previously estimated 25% (95% CI: 16.7%-34.2%) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives. Conclusions: The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non-Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25% to 42.5% at age 80 in all populations analyzed.

AB - Background: Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%-100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non-Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non-Ashkenazi Jews to age 80. Methods: The kin-cohort method was used to estimate penetrance in 474 first-degree relatives of 69 non-Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available. Results: Risk of PD in non-Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5% (95% confidence interval [CI]: 26.3%-65.8%) to age 80, which is not significantly higher than the previously estimated 25% (95% CI: 16.7%-34.2%) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives. Conclusions: The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non-Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25% to 42.5% at age 80 in all populations analyzed.

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KW - Parkinson's disease

KW - penetrance

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