LRRK2 G2019S in families with Parkinson disease who originated from Europe and the Middle East: Evidence of two distinct founding events beginning two millennia ago

Cyrus P. Zabetian, Carolyn M. Hutter, Dora Yearout, Alexis N. Lopez, Stewart A. Factor, Alida Griffith, Berta C. Leis, Thomas D. Bird, John Nutt, Donald S. Higgins, John W. Roberts, Denise M. Kay, Karen L. Edwards, Ali Samii, Haydeh Payami

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90 Scopus citations

Abstract

The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic determinant of Parkinson disease (PD) identified to date. It accounts for 1%-7% of PD in patients of European origin and 20%-40% in Ashkenazi Jews and North African Arabs with PD. Previous studies concluded that patients from these populations all shared a common Middle Eastern founder who lived in the 13th century. We tested this hypothesis by genotyping 25 microsatellite and single-nucleotide-polymorphism markers in 22 families with G2019S and observed two distinct haplotypes. Haplotype 1 was present in 19 families of Ashkenazi Jewish and European ancestry, whereas haplotype 2 occurred in three European American families. Using a maximum-likelihood method, we estimated that the families with haplotype 1 shared a common ancestor 2,250 (95% confidence interval 1,650-3,120) years ago, whereas those with haplotype 2 appeared to share a more recent founder. Our data suggest two separate founding events for G2019S in these populations, beginning at a time that coincides with the Jewish Diasporas.

Original languageEnglish (US)
Pages (from-to)752-758
Number of pages7
JournalAmerican Journal of Human Genetics
Volume79
Issue number4
DOIs
Publication statusPublished - Oct 2006

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ASJC Scopus subject areas

  • Genetics

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