title: Replication analysis of 15 susceptibility loci for nonsyndromic cleft lip with or without cleft palate in an italian population.
abstract: BACKGROUND
  Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformations in humans. Its average global incidence is 1.7 per 1000 live births, with wide variation according to geographical location and ethnicity. Its etiology involves both genetic and environmental factors. The aim of the present study was to confirm genetic association of a selection of 15 candidate nsCL/P loci using an independent sample of the Italian population.
  
  
  METHODS
  At least one single-nucleotide polymorphism (SNP) for each locus was genotyped in 380 nuclear trios.
  
  
  RESULTS
  Transmission disequilibrium analysis revealed significant associations for three variants at two loci (8q24 and 1p22). Two SNPs at 8q24 showed the strongest level of association, the rs987525 (PTDT  = 6.81 × 10(-6) ; homozygous relative risk = 3.60 [95% confidence interval, 2.12-6.13]), and the rs17241253 (PTDT  = 1.03 × 10(-5) ; homozygous relative risk = 3.75 [95% confidence interval, 2.10-6.67]). Four additional loci (at 1q32, 3q12, 8q21, and 10q25) achieved nominally significant p-values. Two SNPs at 1p36 achieved p-values of < 0.1. The present data suggest that 6 of the 15 analyzed nsCL/P risk loci contribute significantly to nsCL/P risk in the Italian population. These include the 1p22 locus, which previous research has implicated predominantly in Asian populations.
  
  
  CONCLUSIONS
  Different loci, including 8q24 and 1p22 have been found associated with nsCL/P in multiple populations. Further efforts are needed to identify causative variants and transfer knowledge to clinical application, such as personal genetic risk assessment.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cura
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Böhmer
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Klamt
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Schünke
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Scapoli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Martinelli
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carinci
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
mesh_terms: D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007558:Italy / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
keywords: association study; genetic loci; nonsyndromic cleft lip with or without cleft palate; polymorphism; replication study