title: Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate.
abstract: Nonsyndromic cleft lip with or without a cleft palate (NSCL/P) is among the most common human congenital birth defects and imposes a substantial physical and financial burden on affected individuals. Here, we conduct a case-control-based GWAS followed by two rounds of replication; we include six independent cohorts from China to elucidate the genetic architecture of NSCL/P in Chinese populations. Using this combined analysis, we identify a new locus at 16p13.3 associated with NSCL/P: rs8049367 between CREBBP and ADCY9 (odds ratio=0.74, P=8.98 × 10(-12)). We confirm that the reported loci at 1q32.2, 10q25.3, 17p13.1 and 20q12 are also involved in NSCL/P development in Chinese populations. Our results provide additional evidence that the rs2235371-related haplotype at 1q32.2 could play a more important role than the previously identified causal variant rs642961 in Chinese populations. These findings provide information on the genetic basis and mechanisms of NSCL/P.
authors.affiliation: 1] Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China [2] The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China [3] CapitalBio Corporation, Beijing 102206, China [4] National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 1] General Hospital of Ningxia Medical University, Yinchuan 750004, China [2] 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: 1] Medical Genetic Center, Guangdong Women and Children Hospital, Guangzhou 511442, China [2] Maternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou 511442, China [3] Biobank of Guangdong Women and Children Hospital, Guangzhou 511442, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Yin
authors.affiliation: 1] Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China [2] Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China [3] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yongchu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: 1] Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China [2] CapitalBio Corporation, Beijing 102206, China [3] National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
authors.forename: Yirui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] General Hospital of Ningxia Medical University, Yinchuan 750004, China [2] National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: 1] Medical Genetic Center, Guangdong Women and Children Hospital, Guangzhou 511442, China [2] Maternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou 511442, China [3] Biobank of Guangdong Women and Children Hospital, Guangzhou 511442, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Lan
authors.affiliation: 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: 1] CapitalBio Corporation, Beijing 102206, China [2] National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wang
authors.affiliation: 1] General Hospital of Ningxia Medical University, Yinchuan 750004, China [2] 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: 1] Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China [2] Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Thalassemia Diagnosis Centre, Guangdong Women and Children Hospital, Guangzhou 511442, China.
authors.forename: Xiaozhuang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: 1] General Hospital of Ningxia Medical University, Yinchuan 750004, China [2] National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: 1] Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China [2] Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Weibing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Dentistry, Guangdong Women and Children Hospital, Guangzhou 511442, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: 1] General Hospital of Ningxia Medical University, Yinchuan 750004, China [2] National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: 1] Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China [2] Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.affiliation: 1] General Hospital of Ningxia Medical University, Yinchuan 750004, China [2] National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China.
authors.forename: Yadi
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1] Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China [2] Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.affiliation: The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: 1] The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China [2] West China College of Stomatology, Sichuan University, Chengdu 610041, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shi
authors.affiliation: 1] Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China [2] CapitalBio Corporation, Beijing 102206, China [3] National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: 1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: 1] Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China [2] Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China [3] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1] General Hospital of Ningxia Medical University, Yinchuan 750004, China [2] National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China.
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Yang
mesh_terms: D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002878:Chromosomes, Human, Pair 1; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide