title: Evaluating eight newly identified susceptibility loci for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population.
abstract: BACKGROUND
  Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is among the most frequently occurring congenital malformations worldwide. The number of genetic loci identified as being involved in NSCL/P etiology was recently increased by a large genome-wide meta-analysis of European and Asian samples. This meta-analysis confirmed all six previously recognized genetic susceptibility loci and identified six novel ones.
  
  
  METHODS
  To investigate which of these 12 loci contribute to NSCL/P risk in an independent sample of distinct ethnicity, we performed a case-control association analysis in a sample of the Mesoamerican population. A total of 153 individuals with NSCL/P (cases) and 337 unaffected controls were included. Top single-nucleotide polymorphisms (SNPs) at 8 of the 12 loci (1p22.1, 1p36, 2p21, 3p11.1, 8q21.3, 13q31.1, 15q22, and 20q12) were analyzed using mass spectroscopy and restriction-length-fragment polymorphism analyses. In a previous study, we had analyzed the remaining four NSCL/P susceptibility regions (IRF6, 8q24, 10q25, and 17q22) in the same sample.
  
  
  RESULTS
  Single-marker association analyses applying allelic, dominant, and recessive models revealed nominal significant associations for four of the eight loci, with two additional loci showing at least a trend of association in the hypothesized direction.
  
  
  CONCLUSIONS
  In combination with results from our previous study using the same sample, our data suggest that the majority of the known NSCL/P susceptibility regions identified to date also confer risk for this malformation in the Mesoamerican population. Birth Defects Research (Part A) 100:43-47, 2014. © 2013 Wiley Periodicals, Inc.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
authors.forename: Philipp
authors.initials: P
authors.lastname: Wahle
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Mario
authors.initials: M
authors.lastname: Paredes-Zenteno
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Muñoz-Jimenez
authors.forename: Rocio
authors.initials: R
authors.lastname: Ortiz-Lopez
authors.forename: Anne C
authors.initials: AC
authors.lastname: Böhmer
authors.forename: Peter
authors.initials: P
authors.lastname: Tessmann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nowak
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.forename: Augusto
authors.initials: A
authors.lastname: Rojas-Martinez
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002971:Cleft Lip / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D007199:Indians, South American; D040582:Inheritance Patterns; D008297:Male; D013058:Mass Spectrometry; D008800:Mexico; D008957:Models, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D005819:Genetic Markers
keywords: Mesoamerican population; case-control studies; cleft lip with or without cleft palate; genetic loci; nonsyndromic; orofacial cleft; polymorphism; single nucleotide