Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Sep;3(5):404-12.
doi: 10.1002/mgg3.151. Epub 2015 May 6.

Novel recruitment strategy to enrich for LRRK2 mutation carriers

Tatiana Foroud  1 , Danielle Smith  1 , Jacqueline Jackson  1 , Jennifer Verbrugge  1 , Cheryl Halter  1 , Leah Wetherill  1 , Katherine Sims  2 , Winnie Xin  2 , Vanessa Arnedo  3 , Shirley Lasch  4 , Kenneth Marek  4 ; Parkinson's Progression Markers Initiativea
Affiliations

Novel recruitment strategy to enrich for LRRK2 mutation carriers

Tatiana Foroud et al. Mol Genet Genomic Med. 2015 Sep.

Abstract

The LRRK2 G2019S mutation is found at higher frequency among Parkinson disease (PD) patients of Ashkenazi Jewish (AJ) ancestry. This study was designed to test whether an internet-based approach could be an effective approach to screen and identify mutation carriers. Individuals with and without PD of AJ ancestry were recruited and consented through an internet-based study website. An algorithm was applied to a series of screening questions to identify individuals at increased risk to carry the LRRK2 G2019S mutation. About 1000 individuals completed the initial screening. Around 741 qualified for mutation testing and 650 were tested. Seventy-two individuals carried at least one LRRK2 G2019S mutation; 38 with PD (12.5%) and 34 without (10.1%). Among the AJ PD participants, each affected first-degree relative increased the likelihood the individual was LRRK2+ [OR = 4.7; 95% confidence interval = (2.4-9.0)]. The same was not observed among the unaffected AJ subjects (P = 0.11). An internet-based approach successfully screened large numbers of individuals to identify those with risk factors increasing the likelihood that they carried a LRRK2 G2019S mutation. A similar approach could be implemented in other disorders to identify individuals for clinical trials, biomarker analyses and other types of research studies.

Keywords: LRRK2; Parkinson disease; genetic testing.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Study overview.
Figure 2
Figure 2
Screening algorithm.
See this image and copyright information in PMC

References

    1. Alcalay RN, Mirelman A, Saunders-Pullman R, Tang MX, Mejia Santana H, Raymond D, et al. Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations. Mov Disord. 2013;28:1966–1971. - PMC - PubMed
    1. Elbaz A, Grigoletto F, Baldereschi M, Breteler MM, Manubens-Bertran JM, Lopez-Pousa S, et al. Familial aggregation of Parkinson’s disease: a population-based case-control study in Europe. EUROPARKINSON Study Group. Neurology. 1999;52:1876–1882. - PubMed
    1. Goldwurm S, Zini M, Mariani L, Tesei S, Miceli R, Sironi F, et al. Evaluation of LRRK2 G2019S penetrance: relevance for genetic counseling in Parkinson disease. Neurology. 2007;68:1141–1143. - PubMed
    1. Grinzaid KA, Page PZ, Denton JJ, Ginsberg J. Creation of a National, At-home Model for Ashkenazi Jewish Carrier Screening. J Genet Couns. 2014 [Epub ahead of print] - PubMed
    1. Healy DG, Falchi M, O’Sullivan SS, Bonifati V, Durr A, Bressman S, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol. 2008;7:583–590. - PMC - PubMed

LinkOut - more resources