title: Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia.
abstract: Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P=2.15 × 10(-120)) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis. We then perform whole-genome sequencing on 21 samples from the case cohort, and identify several novel loss-of-function mutations within the associated loci. Our results provide new insights into genetic background of craniofacial microsomia.
authors: Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.|Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.
authors: Yong-Biao
authors: YB
authors: Zhang
authors: Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.
authors: Jintian
authors: J
authors: Hu
authors: Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.|Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
authors: Jiao
authors: J
authors: Zhang
authors: Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.
authors: Xu
authors: X
authors: Zhou
authors: Department of Cardiology, Beijing Anzhen Hospital of the Capital University of Medical Sciences, Beijing 100029, China.
authors: Xin
authors: X
authors: Li
authors: Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Chaohao
authors: C
authors: Gu
authors: Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.
authors: Tun
authors: T
authors: Liu
authors: Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.
authors: Yangchun
authors: Y
authors: Xie
authors: Beijing KPS biotechnology, Beijing 102206, China.
authors: Jiqiang
authors: J
authors: Liu
authors: Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Mingliang
authors: M
authors: Gu
authors: Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Panpan
authors: P
authors: Wang
authors: Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Tingting
authors: T
authors: Wu
authors: Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.
authors: Jin
authors: J
authors: Qian
authors: Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.
authors: Yue
authors: Y
authors: Wang
authors: Department of Internal Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors: Xiaoqun
authors: X
authors: Dong
authors: Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Jun
authors: J
authors: Yu
authors: Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing 100144, China.
authors: Qingguo
authors: Q
authors: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002642:Chick Embryo; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D051518:Fibroblast Growth Factor 3 / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006053:Goldenhar Syndrome / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D016015:Logistic Models; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009432:Neural Crest / Q000196:embryology; D039943:Neuropilin-2 / Q000235:genetics; D054803:Phospholipase C delta / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044023:Receptor, Endothelin B / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D039961:Semaphorins / Q000235:genetics; D055815:Young Adult; D000097905:Roundabout Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D051518:Fibroblast Growth Factor 3; D050990:GATA3 Transcription Factor; D058851:GPI-Linked Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; D054803:Phospholipase C delta; D044023:Receptor, Endothelin B; D011971:Receptors, Immunologic; D039961:Semaphorins; D000097905:Roundabout Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1; C000588596:EDNRB protein, human; C496444:FGF3 protein, human; C494749:GATA3 protein, human; C084958:GBX2 protein, human; C436492:KLF12 protein, human; C118753:SEMA7A protein, human; C000596976:SHROOM3 protein, human; C581308:neuropilin-2, human; C518028:PLCD3 protein, human