Dataset Information

A powerful genome-wide feasible approach to detect parent-of-origin effects in studies of quantitative traits.

ABSTRACT: There is currently a lot of interest in the role of genomic imprinting in mammalian development. Many human diseases, such as cancer, obesity, diabetes and behavioral traits, may be related to imprinted genes. When searching for genes related to complex disorders, the power of genome-wide association analysis can be improved by introducing parent-of-origin effects into the analyses. For quantitative traits, family-based TDT analysis has successfully implemented such an approach. Although attractive for several reasons, TDT-based tests are known to be less powerful than methods based on measured genotype approaches. In this study, we describe a fast, powerful method for detecting parent-of-origin effects in studies of quantitative traits using a measured genotype framework. First, for each locus studied, we estimate the probabilities of an allele's parental origin using multipoint haplotype reconstruction. Next, we introduce the parental origin of these alleles as a covariate in regression models during the second step of GRAMMAR, a fast approximation to the measured genotype approach. We show that, compared with a TDT-based analysis, our method has a higher power to detect a locus exhibiting a parent-of-origin effect. Moreover, our method is applicable to a wider range of data, including pedigree structures that are not very informative for TDT. The method gives no false positives in the absence of parent-of-origin effects, under both additive and dominant models. As this method is an extension of the rapid GRAMMAR analysis, it is fast enough to be suitable for genome-wide association scans.

SUBMITTER: Belonogova NM

PROVIDER: S-EPMC2987227 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A powerful genome-wide feasible approach to detect parent-of-origin effects in studies of quantitative traits.

Belonogova Nadezhda M NM Axenovich Tatiana I TI Aulchenko Yurii S YS

European journal of human genetics : EJHG 20091007 3

There is currently a lot of interest in the role of genomic imprinting in mammalian development. Many human diseases, such as cancer, obesity, diabetes and behavioral traits, may be related to imprinted genes. When searching for genes related to complex disorders, the power of genome-wide association analysis can be improved by introducing parent-of-origin effects into the analyses. For quantitative traits, family-based TDT analysis has successfully implemented such an approach. Although attract ...[more]

PMID: 19809476

Similar Datasets

Project description:BACKGROUND:Genomic imprinting is one of the well-known epigenetic factors causing the association between traits and genes, and has generally been examined by detecting parent-of-origin effects of alleles. A lot of methods have been proposed to test for parent-of-origin effects on autosomes based on nuclear families and general pedigrees. Although these parent-of-origin effects tests on autosomes have been available for more than 15 years, there has been no statistical test developed to test for parent-of-origin effects on X chromosome, until the parental-asymmetry test on X chromosome (XPAT) and its extensions were recently proposed. However, these methods on X chromosome are only applicable to nuclear families and thus are not suitable for general pedigrees. RESULTS:In this article, we propose the pedigree parental-asymmetry test on X chromosome (XPPAT) statistic to test for parent-of-origin effects in the presence of association, which can accommodate general pedigrees. When there are missing genotypes in some pedigrees, we further develop the Monte Carlo pedigree parental-asymmetry test on X chromosome (XMCPPAT) to test for parent-of-origin effects, by inferring the missing genotypes given the observed genotypes based on a Monte Carlo estimation. An extensive simulation study has been carried out to investigate the type I error rates and the powers of the proposed tests. Our simulation results show that the proposed methods control the size well under the null hypothesis of no parent-of-origin effects. Moreover, XMCPPAT substantially outperforms the existing tests and has a much higher power than XPPAT which only uses complete nuclear families (with both parents) from pedigrees. We also apply the proposed methods to analyze rheumatoid arthritis data for their practical use. CONCLUSIONS:The proposed XPPAT and XMCPPAT test statistics are valid and powerful in detecting parent-of-origin effects on X chromosome for qualitative traits based on general pedigrees and thus are recommended.

Dataset Information

A powerful genome-wide feasible approach to detect parent-of-origin effects in studies of quantitative traits.

Publications

A powerful genome-wide feasible approach to detect parent-of-origin effects in studies of quantitative traits.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets