Lingxue Bu1, Qianqian Chen2,3, Hong Wang2,4, Tianxiao Zhang5, Jacqueline B Hetmanski6, Holger Schwender7, Margaret Parker6, Yah-Huei Wu Chou8, Vincent Yeow9, Samuel S Chong10, Bo Zhang11, Ethylin Wang Jabs12, Alan F Scott13, Terri H Beaty6. 1. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Qingdao University, Qingdao, China. 2. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. 3. National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China. 4. Ministry of Health KeyLaboratory of Reproductive Health, Beijing, China. 5. Division of Biology and Biomedical Sciences, Washington University, St. Louis, Missouri. 6. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 7. Mathematical Institute, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. 8. Department of Medical Research, Chang Gung Memorial Hospital, Taipei, Taiwan. 9. Department of Plastic Surgery, K K Women's and Children's Hospital, Singapore. 10. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore. 11. Department of Biomedical Engineering, Xi'an JiaoTong University, Xi'an, China. 12. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland. 13. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND: The forkhead box F2 gene (FOXF2) located in chromosome 6p25.3 has been shown to play a crucial role in palatal development in mouse and rat models. To date, no evidence of linkage or association has been reported for this gene in humans with oral clefts. METHODS: Allelic transmission disequilibrium tests were used to robustly assess evidence of linkage and association with nonsyndromic cleft lip with or without cleft palate for nine single nucleotide polymorphisms (SNPs) in and around FOXF2 in both Asian and European trios using PLINK. RESULTS: Statistically significant evidence of linkage and association was shown for two SNPs (rs1711968 and rs732835) in 216 Asian trios where the empiric P values with permutation tests were 0.0016 and 0.005, respectively. The corresponding estimated odds ratios for carrying the minor allele at these SNPs were 2.05 (95% confidence interval = 1.41, 2.98) and 1.77 (95% confidence interval = 1.26, 2.49), respectively. CONCLUSION: Our results provided statistical evidence of linkage and association between FOXF2 and nonsyndromic cleft lip with or without cleft palate.
BACKGROUND: The forkhead box F2 gene (FOXF2) located in chromosome 6p25.3 has been shown to play a crucial role in palatal development in mouse and rat models. To date, no evidence of linkage or association has been reported for this gene in humans with oral clefts. METHODS: Allelic transmission disequilibrium tests were used to robustly assess evidence of linkage and association with nonsyndromic cleft lip with or without cleft palate for nine single nucleotide polymorphisms (SNPs) in and around FOXF2 in both Asian and European trios using PLINK. RESULTS: Statistically significant evidence of linkage and association was shown for two SNPs (rs1711968 and rs732835) in 216 Asian trios where the empiric P values with permutation tests were 0.0016 and 0.005, respectively. The corresponding estimated odds ratios for carrying the minor allele at these SNPs were 2.05 (95% confidence interval = 1.41, 2.98) and 1.77 (95% confidence interval = 1.26, 2.49), respectively. CONCLUSION: Our results provided statistical evidence of linkage and association between FOXF2 and nonsyndromic cleft lip with or without cleft palate.
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