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Genomewide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36

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Abstract

The development of refractive error is mediated by both environmental and genetic factors. We performed regression-based quantitative trait locus (QTL) linkage analysis on Ashkenazi Jewish families to identify regions in the genome responsible for ocular refraction. We measured refractive error on individuals in 49 multi-generational American families of Ashkenazi Jewish descent. The average family size was 11.1 individuals and was composed of 2.7 generations. Recruitment criteria specified that each family contain at least two myopic members. The mean spherical equivalent refractive error in the sample was −3.46D (SD=3.29) and 87% of individuals were myopic. Microsatellite genotyping with 387 markers was performed on 411 individuals. We performed multipoint regression-based linkage analysis for ocular refraction and a log transformation of the trait using the statistical package Merlin-Regress. Empirical genomewide significance levels were estimated through gene-dropping simulations by generating random genotypes at each of the 387 markers in 200 replicates of our pedigrees. Maximum LOD scores of 9.5 for ocular refraction and 8.7 for log-transformed refraction (LTR) were observed at 49.1 cM on chromosome 1p36 between markers D1S552 and D1S1622. The empirical genomewide significance levels were P=0.065 for ocular refraction and P<0.005 for LTR, providing strong evidence for linkage of refraction to this locus. The inter-marker region containing the peak spans 11 Mb and contains approximately 189 genes. Conclusion: We found genomewide significant evidence for linkage of refractive error to a novel QTL on chromosome 1p36 in an Ashkenazi Jewish population.

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Acknowledgements

This study was supported in part by U.S. Public Health National Eye Institute grant EY12226 (DS) and in part by funds from the intramural program of the National Human Genome Research Institute, NIH (JEB-W, GI, RW). RW also received a William C. Ezell-CIBA Vision Fellowship from the American Optometric Foundation. The authors thank the families for their participation in the study and Dr. Reuvain Shanik and Rabbi Yitzchok Rozsansky for their enthusiasm and effort on the project. Genotyping services were provided by CIDR. CIDR is fully funded through a federal contract from the National Institutes of Health to Johns Hopkins University (contract number N01-HG-65403).

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Robert Wojciechowski

  2. Inherited Disease Research Branch, National Human Genome Research Institute (NIH), 333 Cassell Dr., Suite 1200, Baltimore, MD, 21224, USA

    Robert Wojciechowski, Grace Ibay & Joan E. Bailey-Wilson

  3. Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA

    Chris Moy, Lauren Reider & Dwight Stambolian

  4. Pennsylvania College of Optometry, Philadelphia, PA, USA

    Elise Ciner

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  1. Robert Wojciechowski
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Correspondence to Robert Wojciechowski.

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Wojciechowski, R., Moy, C., Ciner, E. et al. Genomewide scan in Ashkenazi Jewish families demonstrates evidence of linkage of ocular refraction to a QTL on chromosome 1p36. Hum Genet 119, 389–399 (2006). https://doi.org/10.1007/s00439-006-0153-x

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  • DOI: https://doi.org/10.1007/s00439-006-0153-x

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