@article{01da3926d4c24bfdbd78b47f485b0e91,
title = "Exploring the interaction between FGF Genes and T-box genes among chinese nonsyndromic cleft lip with or without cleft palate case-parent trios",
abstract = "Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect. Genetic variants causing syndromic orofacial clefts can also contribute to the etiology of NSCL/P. The purpose of the present study was to explore gene–gene (G × G) interaction using common single nucleotide polymorphic (SNP) markers in fibroblast growth factor (FGF) family and its receptors and T-box genes, which were associated with syndromic orofacial clefts. Our study was conducted in 806 Chinese NSCL/P case-parent trios drawn from an international consortium. A total of 252 SNPs in FGF8, FGF10, FGFR1, FGFR2, and TBX5 passed the quality control criteria and were included in the analysis. The interactions between SNPs in different genes were assessed using Cordell's method, which fitted a conditional logistic regression model. The analysis was performed using the R-package trio (Version 3.8.0). Bonferroni correction was used to adjust for multiple comparisons, and the overall significance threshold was set as P = 1.98 × 10−4 (0.05/252). Conditional logistic regression revealed the most significant interaction between rs2330542 in FGF10 and rs1946295 in TBX5, which remained significant (P = 9.63 × 10−6) after Bonferroni correction. The relative risk of allele C in rs2330542 (FGF10) was 1.02 (95%CI 0.81–1.28), while the relative risk was 1.42 (95%CI 1.03–1.97) when the exposure was a combination of allele C in rs2330542 and allele A in rs1946295 (TBX5). Our findings confirmed the importance of considering G × G interaction when exploring the genetic risk factors of NSCL/P. Further investigations are warranted to validate the potential interaction and reveal the biological function of FGF10/FGFR2/TBX5. Environ. Mol. Mutagen. 2019.",
keywords = "FGF, T-box genes, case-parent trios, gene–gene interaction, oral clefts",
author = "Wenyong Li and Mengying Wang and Ren Zhou and Siyue Wang and Hongchen Zheng and Dongjing Liu and Zhibo Zhou and Hongping Zhu and Tao Wu and Beaty, {Terri H.}",
note = "Funding Information: The data in our study were a collaborative effort among many groups. We sincerely thank all families who participated in this study, and we gratefully acknowledge the invaluable assistance of the staff who made this work possible. The International Cleft Consortium including genotyping and analysis was supported by the National Institute for Dental and Craniofacial Research through U01-DE-018993; “International Consortium to Identify Genes & Interactions Controlling Oral Clefts”, 2007–2009. We acknowledge the invaluable contributions of J.C. Murray (University of Iowa), R. G. Munger (Utah State University), A. J. Wilcox (NIEHS), R. J. Redett (Johns Hopkins University), X. Ye (Wuhan University), S. Huang (Peking Medical College), V. Yeow (KKWCH), S. S. Chong (National University of Singapore), E. W. Jabs (Johns Hopkins University), B. Shi (Sichuan University), S. H. Jee (Yonsei University), and A. F. Scott (Johns Hopkins University). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). We thank for the work of the Coordinating Center (directed by B. Weir and C. Laurie of the University of Washington) in data cleaning and preparation of these trios for submission to the Database for Genotypes and Phenotypes (dbGaP: http://www.ncbi.nlm.nih.gov/). This research was also supported by grants from the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank the Smile Train Foundation for supporting cleft research in China. This study also received funding support from National Natural Science Foundation of China (81102178 and 81573225, PI: Tao Wu) and Beijing Natural Science Foundation of China (7172115, PI: Tao Wu) and Peking University Health Science Center Interdisciplinary Research Fund (BMU2017MX018, PI: Hongping Zhu and Tao Wu). Funding Information: Grant sponsor: Peking University Health Science Center Interdisciplinary Research Fund; Grant number: BMU2017MX018. Grant sponsor: Beijing Natural Science Foundation of China; Grant number: 7172115. Grant sponsor: National Natural Science Foundation of China; Grant numbers: 81573225; 81102178. Grant sponsor: National Institute of Environmental Health Sciences. Grant sponsor: National Institute for Dental and Craniofacial Research; Grant number: U01-DE-018993. Funding Information: The data in our study were a collaborative effort among many groups. We sincerely thank all families who participated in this study, and we gratefully acknowledge the invaluable assistance of the staff who made this work possible. The International Cleft Consortium including genotyping and analysis was supported by the National Institute for Dental and Craniofacial Research through U01-DE-018993; ?International Consortium to Identify Genes & Interactions Controlling Oral Clefts?, 2007?2009. We acknowledge the invaluable contributions of J.C. Murray (University of Iowa), R. G. Munger (Utah State University), A. J. Wilcox (NIEHS), R. J. Redett (Johns Hopkins University), X. Ye (Wuhan University), S. Huang (Peking Medical College), V. Yeow (KKWCH), S. S. Chong (National University of Singapore), E. W. Jabs (Johns Hopkins University), B. Shi (Sichuan University), S. H. Jee (Yonsei University), and A. F. Scott (Johns Hopkins University). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). We thank for the work of the Coordinating Center (directed by B. Weir and C. Laurie of the University of Washington) in data cleaning and preparation of these trios for submission to the Database for Genotypes and Phenotypes (dbGaP: http://www.ncbi.nlm.nih.gov/). This research was also supported by grants from the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank the Smile Train Foundation for supporting cleft research in China. This study also received funding support from National Natural Science Foundation of China (81102178 and 81573225, PI: Tao Wu) and Beijing Natural Science Foundation of China (7172115, PI: Tao Wu) and Peking University Health Science Center Interdisciplinary Research Fund (BMU2017MX018, PI: Hongping Zhu and Tao Wu). Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2019",
doi = "10.1002/em.22286",
language = "English (US)",
volume = "60",
pages = "602--606",
journal = "Environmental and molecular mutagenesis",
issn = "0893-6692",
publisher = "Wiley-Liss Inc.",
number = "7",
}