Candidate Pathway Based Analysis for Cleft Lip with or without Cleft Palate
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Tian-Xiao Zhang
The objective of this research was to identify potential biological pathways associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and to explore the potential biological mechanisms underlying these associated pathways on risk of NSCL/P. This project was based on the dataset of a previously published genome-wide association (GWA) study on NSCL/P (Beaty et al. 2010). Case-parent trios used here originated from an international consortium (The Gene, Environment Association Studies consortium, GENEVA) formed in 2007. A total of 5,742 individuals from 1,908 CL/P case-parents trios (1,591 complete trios and 317 incomplete trios where one parent was missing) were collected and genotyped using the Illumina Human610-Quad array. Candidate pathways were selected using a list of 356 genes that may be related to oral clefts. In total, 42 candidate pathways, which included 1,564 genes and 40,208 SNPs were tested. Using a pathway-based analysis approach proposed by Wang et al (2007), we conducted a permutation-based test to assess the statistical significance of the nominal p-values of 42 candidate pathways. The analysis revealed several pathways yielding nominally significant p-values. However, controlling for the family wise error rate, none of these pathways could retain statistical significance. Nominal p-values of these pathways were concentrated at the lower tail of the distribution, with more than expected low p-values. A permutation based test for examining this type of distribution pattern yielded an overall p-value of 0.029. Thus, while this pathway-based analysis did not yield a clear significant result for any particular pathway, we conclude that one or more of the genes and pathways considered here likely do play a role in oral clefting.
©2012 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
Articles in the same Issue
- Editorial Introduction
- Special Issue on Computational Statistical Methods for Genomics and Systems Biology
- Article
- A Generalized Hidden Markov Model for Determining Sequence-based Predictors of Nucleosome Positioning
- Gene Filtering in the Analysis of Illumina Microarray Experiments
- Principal Components of Heritability for High Dimension Quantitative Traits and General Pedigrees
- Bayesian Sparsity-Path-Analysis of Genetic Association Signal using Generalized t Priors
- A Family-Based Probabilistic Method for Capturing De Novo Mutations from High-Throughput Short-Read Sequencing Data
- Adjusting for Spurious Gene-by-Environment Interaction Using Case-Parent Triads
- Querying Genomic Databases: Refining the Connectivity Map
- A Model-Based Analysis to Infer the Functional Content of a Gene List
- Candidate Pathway Based Analysis for Cleft Lip with or without Cleft Palate
- Improving Pedigree-based Linkage Analysis by Estimating Coancestry Among Families
Articles in the same Issue
- Editorial Introduction
- Special Issue on Computational Statistical Methods for Genomics and Systems Biology
- Article
- A Generalized Hidden Markov Model for Determining Sequence-based Predictors of Nucleosome Positioning
- Gene Filtering in the Analysis of Illumina Microarray Experiments
- Principal Components of Heritability for High Dimension Quantitative Traits and General Pedigrees
- Bayesian Sparsity-Path-Analysis of Genetic Association Signal using Generalized t Priors
- A Family-Based Probabilistic Method for Capturing De Novo Mutations from High-Throughput Short-Read Sequencing Data
- Adjusting for Spurious Gene-by-Environment Interaction Using Case-Parent Triads
- Querying Genomic Databases: Refining the Connectivity Map
- A Model-Based Analysis to Infer the Functional Content of a Gene List
- Candidate Pathway Based Analysis for Cleft Lip with or without Cleft Palate
- Improving Pedigree-based Linkage Analysis by Estimating Coancestry Among Families
