title: Association study between Van der Woude Syndrome causative gene GRHL3 and nonsyndromic cleft lip with or without cleft palate in a Chinese cohort.
abstract: Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects worldwide and is characterized by abnormalities of the orofacial structure. Syndromic CL/P is mainly caused by Mendelian disorders such as Van der Woude Syndrome (VWS). However, >70% of CL/P cases are nonsyndromic, characterized by isolated orofacial cleft without any known syndrome. The etiology of nonsyndromic CL/P (NSCL/P) remains elusive, but it has been suggested that causative genes of syndromic CL/P might also contribute to NSCL/P. As such, the VWS causative gene IRF6 has been extensively studied in NSCL/P. Recently, GRHL3 was identified as another VWS causative gene. Thus, it may be a novel candidate gene for NSCL/P. In the present study, we genotyped 10 tag SNPs covering GRHL3 and performed association analysis with NSCL/P in 504 cases and 455 healthy controls. Our preliminary results identified rs10903078, rs4638975, and a haplotype rs10903078-rs6659209 of GRHL3 that exceeded the significance threshold (p<0.05), though none survived Bonferroni correction for multiple comparisons. As the first study between GRHL3 and NSCL/P, the contribution of this gene to NSCL/P etiology should be interpreted with caution based on existing evidence. Further, the robustness of association between GRHL3 and NSCL/P should be further validated in expanded cohorts.
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China; CapitalBio Corporation, Beijing 102206, China; National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
authors.forename: Yirui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China; CapitalBio Corporation, Beijing 102206, China; National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China; The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Ningxia Medical University, Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, China; National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yongchu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China; West China College of Stomatology, Sichuan University, Chengdu 610041, China.
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Ningxia Medical University, Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Ma
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.affiliation: Medical Genetic Center, Guangdong, Women and Children Hospital, Guangzhou 511442, China; Maternal and Children Metabolic-Genetic Key Laboratory, Guangdong, Women and Children Hospital, Guangzhou 511442, China; Biobank of Guangdong Women and Children Hospital, Guangzhou 511442, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Lan
authors.affiliation: CapitalBio Corporation, Beijing 102206, China; National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, United States.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Ningxia Medical University, Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Yang
authors.affiliation: CapitalBio Corporation, Beijing 102206, China; National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Jiang
authors.affiliation: General Hospital of Ningxia Medical University, Yinchuan 750004, China; National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Medical Genetic Center, Guangdong, Women and Children Hospital, Guangzhou 511442, China; Maternal and Children Metabolic-Genetic Key Laboratory, Guangdong, Women and Children Hospital, Guangzhou 511442, China; Biobank of Guangdong Women and Children Hospital, Guangzhou 511442, China. Electronic address: yinaiwa@vip.126.com.
authors.forename: Aihua
authors.initials: A
authors.lastname: Yin
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China; CapitalBio Corporation, Beijing 102206, China; National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China. Electronic address: lw603@njmu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Ningxia Medical University, Yinchuan 750004, China; General Hospital of Ningxia Medical University, Yinchuan 750004, China; National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China. Electronic address: nyfyyyx@126.com.
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China; West China College of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address: shibingcn@vip.sina.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Shi
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D003560:Cysts / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008046:Lip / Q000002:abnormalities* / Q000473:pathology; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C473143:GRHL3 protein, human; D014157:Transcription Factors
keywords: GRHL3; NSCL/P; SNP; Van der Woude Syndrome