Statistical Applications in Genetics and Molecular Biology
Editor-in-Chief: Stumpf, Michael P.H.
IMPACT FACTOR increased in 2015: 1.265
5-year IMPACT FACTOR: 1.423
Rank 42 out of 123 in category Statistics & Probability in the 2015 Thomson Reuters Journal Citation Report/Science Edition
SCImago Journal Rank (SJR) 2015: 0.954
Source Normalized Impact per Paper (SNIP) 2015: 0.554
Impact per Publication (IPP) 2015: 1.061
Mathematical Citation Quotient (MCQ) 2015: 0.06
Candidate Pathway Based Analysis for Cleft Lip with or without Cleft Palate
1Johns Hopkins University
2Johns Hopkins University
3Johns Hopkins University
Citation Information: Statistical Applications in Genetics and Molecular Biology. Volume 11, Issue 2, ISSN (Online) 1544-6115, DOI: 10.2202/1544-6115.1717, January 2012
- Published Online:
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.