Elisabet Mondragón, Roy N. Alcalay, Rachel Saunders-Pullman, Yuanjia Wang, Karen Marder, Chiara Siri, Stefano Goldwurm, Dolores Vilas, Claustre Pont-Sunyer, , Eduardo Tolosa, Rosanna Asselta, Daniela Berg, Farah Kausar, Nir Giladi, Birgitt Schüle, Graziella Mangone, Jean-Christophe Corvol, Kathrin Brockmann, Anat Mirelman, Taneera Ghate, Alexis Brice, Tatiana Foroud, Suzanne Lesage, Susan Bressman, Javier Ruiz-Martinez, Helen Mejia-Santana, Connie Marras, Annie J. Lee
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. © 2017 International Parkinson and Movement Disorder Society
