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.