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Candidate Pathway Based Analysis for Cleft Lip with or without Cleft Palate

Author

Listed:
  • Zhang Tian-Xiao

    (Johns Hopkins University)

  • Beaty Terri H.

    (Johns Hopkins University)

  • Ruczinski Ingo

    (Johns Hopkins University)

Abstract

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.

Suggested Citation

  • Zhang Tian-Xiao & Beaty Terri H. & Ruczinski Ingo, 2012. "Candidate Pathway Based Analysis for Cleft Lip with or without Cleft Palate," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 11(2), pages 1-21, January.
    • Handle: RePEc:bpj:sagmbi:v:11:y:2012:i:2:n:10
    DOI: 10.2202/1544-6115.1717
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    References listed on IDEAS

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    1. Hariklia Eleftherohorinou & Victoria Wright & Clive Hoggart & Anna-Liisa Hartikainen & Marjo-Riitta Jarvelin & David Balding & Lachlan Coin & Michael Levin, 2009. "Pathway Analysis of GWAS Provides New Insights into Genetic Susceptibility to 3 Inflammatory Diseases," PLOS ONE, Public Library of Science, vol. 4(11), pages 1-11, November.
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    Cited by:

    1. Olga A Vsevolozhskaya & Min Shi & Fengjiao Hu & Dmitri V Zaykin, 2020. "DOT: Gene-set analysis by combining decorrelated association statistics," PLOS Computational Biology, Public Library of Science, vol. 16(4), pages 1-25, April.

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