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Imprinting detection by extending a regression-based QTL analysis method

Abstract

We present an extension of a regression-based quantitative-trait linkage analysis method to incorporate parent-of-origin effects. We separately regressed total, paternal, and maternal IBD sharing on traits’ squared sums and differences. We also developed a test for imprinting that indicates whether there is any difference between the paternal and maternal regression coefficients. Since this method treats the identity-by-descent information as the dependent variable that is conditioned on the trait, it can be readily applied to data from complex ascertainment processes. We performed a simulation study to examine the performance of the method. We found that when using empirical critical values, the method shows identical or higher power compared to existing methods for evaluation of parent-of-origin effect in linkage analysis of quantitative traits. Missing parental genotypes increase the type I error rate of the linkage test and decrease the power of the imprinting test. When the major gene has a low heritability, the power of the method decreases considerably, but the statistical tests still perform well. We also applied a permutation algorithm, which ensures the appropriate type I error rate for the test for imprinting. The method was applied to a data from a study of 6 body size related measures and 23 loci on chromosome 7 for 255 nuclear families. Multipoint identities-by-descent (IBD) were obtained using a modification of the SIMWALK 2 program. A parent-of-origin effect consistent with maternal imprinting was suggested at 99.67–111.26 Mb for body mass index, bioelectrical impedance analysis, waist circumference, and leptin concentration.

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Acknowledgments

The work was supported by the National Institutes of Health grant ES09912. We thank Drs. Pak C. Sham and Goncalo R. Abecasis for their help regarding the regression model and its implementation in Merlin-Regress, and Mrs. Wei Chen for her help with the simulation setup.

Author information

Correspondence to Olga Y. Gorlova.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00439-007-0426-z

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Appendices

Appendix

Electronic-Database Information

The URLs for data presented herein are as follows: American Diabetes Association, http://www.diabetes.org/about-diabetes.jspOnline Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/. The software developed in this study is available from the author free of charge upon request.

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Gorlova, O.Y., Lei, L., Zhu, D. et al. Imprinting detection by extending a regression-based QTL analysis method. Hum Genet 122, 159–174 (2007). https://doi.org/10.1007/s00439-007-0387-2

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Keywords

  • Waist Circumference
  • Standard Normal Distribution
  • Parental Genotype
  • Base Case Scenario
  • Linkage Test