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

Funding

FundersFunder number
German Parkinson's Disease Association, Bundesministerium für Wirtschaft und Energie
Investissements d'avenirANR-10-IAIHU-06
Janssen Pharmaceutica N.V.
Learning Technology and Innovation
Lysosomal Therapeutic Inc.
NNE
Parkinson Fonds Deutschland gGmbH
Smart Foundation
Spanish Network for Research on Neurodegenerative Disorders-Instituto Carlos IIIR01NS037167
Teva Network of Excellence in Neuroscience
National Institutes of HealthF31AG054095, NS073671, NS082062, TL1-TR000082
National Institutes of Health
National Institute of Neurological Disorders and StrokeR56NS036630
National Institute of Neurological Disorders and Stroke
Michael J. Fox Foundation for Parkinson's ResearchK02NS080915
Michael J. Fox Foundation for Parkinson's Research
Huntington's Disease Society of America
National Parkinson Foundation
Parkinson's Disease Foundation
Bachmann-Strauss Dystonia and Parkinson Foundation
Dystonia Medical Research Foundation
Genzyme
Novartis
CHDI Foundation1UL1 RR024156-01, NS036630, U01NS052592
CHDI Foundation
Teva Pharmaceutical Industries
Cure Huntington's Disease Initiative
Seventh Framework Programme
Horizon Pharma
Parkinson Study Group
Acorda Therapeutics
Canadian Institutes of Health ResearchGTB12001
Canadian Institutes of Health Research
Bundesministerium für Bildung und Forschung
Fondazione Telethon
Israel Science Foundation
Bundesministerium für Wirtschaft und Energie
H. Lundbeck A/S

    Keywords

    • LRRK2
    • Parkinson's disease
    • penetrance

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