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Implications for health and disease in the genetic signature of the Ashkenazi Jewish population

Saurav Guha1, Jeffrey A Rosenfeld1, Anil K Malhotra12345, Annette T Lee6, Peter K Gregersen56, John M Kane12345, Itsik Pe'er7, Ariel Darvasi8 and Todd Lencz12345*

Author Affiliations

1 Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of the North Shore - Long Island Jewish Health System, 75-59, 263rd St Glen Oaks, NY 11004, USA

2 Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA

3 Department of Psychiatry and Behavioral Science, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Ave, Bronx, NY 10461, USA

4 Department of Psychiatry, Hofstra University School of Medicine, Hempstead, NY 11549, USA

5 Department of Molecular Medicine, Hofstra University School of Medicine, Hempstead, NY 11549, USA

6 Robert S Boas Center for Human Genetics and Genomics, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA

7 Department of Computer Science, Columbia University, 500 W 120th St New York, NY 10027, USA

8 Department of Genetics The Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, 91904, Israel

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Genome Biology 2012, 13:R2  doi:10.1186/gb-2012-13-1-r2

Published: 25 January 2012



Relatively small, reproductively isolated populations with reduced genetic diversity may have advantages for genomewide association mapping in disease genetics. The Ashkenazi Jewish population represents a unique population for study based on its recent (< 1,000 year) history of a limited number of founders, population bottlenecks and tradition of marriage within the community. We genotyped more than 1,300 Ashkenazi Jewish healthy volunteers from the Hebrew University Genetic Resource with the Illumina HumanOmni1-Quad platform. Comparison of the genotyping data with that of neighboring European and Asian populations enabled the Ashkenazi Jewish-specific component of the variance to be characterized with respect to disease-relevant alleles and pathways.


Using clustering, principal components, and pairwise genetic distance as converging approaches, we identified an Ashkenazi Jewish-specific genetic signature that differentiated these subjects from both European and Middle Eastern samples. Most notably, gene ontology analysis of the Ashkenazi Jewish genetic signature revealed an enrichment of genes functioning in transepithelial chloride transport, such as CFTR, and in equilibrioception, potentially shedding light on cystic fibrosis, Usher syndrome and other diseases over-represented in the Ashkenazi Jewish population. Results also impact risk profiles for autoimmune and metabolic disorders in this population. Finally, residual intra-Ashkenazi population structure was minimal, primarily determined by class 1 MHC alleles, and not related to host country of origin.


The Ashkenazi Jewish population is of potential utility in disease-mapping studies due to its relative homogeneity and distinct genomic signature. Results suggest that Ashkenazi-associated disease genes may be components of population-specific genomic differences in key functional pathways.