Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate

Nat Commun. 2015 Mar 16:6:6414. doi: 10.1038/ncomms7414.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • China / epidemiology
  • Chromosomes, Human, Pair 1
  • Cleft Lip / epidemiology
  • Cleft Lip / genetics*
  • Cleft Palate / epidemiology
  • Cleft Palate / genetics*
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Haplotypes
  • Humans
  • Infant, Newborn
  • Logistic Models
  • Male
  • Odds Ratio
  • Polymorphism, Single Nucleotide