title: ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population.
abstract: BACKGROUND
  The receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans. The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.
  
  
  METHODS
  Here we tested 38 eligible single-nucleotide polymorphisms (SNPs) in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland. Family Based Association Test was used to test for deviation from Mendelian inheritance. Plink software was used to test potential parent of origin effect. Possible maternally mediated in utero effects were assessed using the TRIad Multi-Marker approach under an assumption of mating symmetry in the population.
  
  
  RESULTS
  Significant evidence of linkage and association was shown for 3 SNPs (rs7858435, rs10820914 and rs3905385) among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests. P values for these 3 SNPs equaled to 0.000068, 0.000115 and 0.000464 respectively which were all less than the significance level (0.05/38 = 0.0013) adjusted by strict Bonferroni correction. Relevant odds ratios for the risk allele were 3.42 (1.80 - 6.50), 3.45 (1.75 - 6.67) and 2.94 (1.56 - 5.56), respectively. Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate. Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.
  
  
  CONCLUSIONS
  Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.
authors.affiliation: Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China. hwang2010@yahoo.cn
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.forename: Kung Yee
authors.initials: KY
authors.lastname: Liang
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Redett
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Raymond
authors.forename: Yah-Huei Wu
authors.initials: YH
authors.lastname: Chou
authors.forename: Philip Kuo-Ting
authors.initials: PK
authors.lastname: Chen
authors.forename: Vincent
authors.initials: V
authors.lastname: Yeow
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Chong
authors.forename: Felicia Sh
authors.initials: FSh
authors.lastname: Cheah
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
authors.forename: Alan F
authors.initials: AF
authors.lastname: Scott
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
mesh_terms: D044466:Asian People / Q000235:genetics; D002971:Cleft Lip / Q000235:genetics; D002972:Cleft Palate / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics*
chemical_list: C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors