Nonsyndromic cleft lip with or without cleft palate (NSCL/P), the most common type of orofacial clefting, is one of the most frequent congenital defects. Based on epidemiological data, NSCL/P can be distinguished from nonsyndromic cleft palate only (NSCPO). Both phenotypes have a complex etiology and environmental and genetic factors are involved in their development. To date, genome-wide association studies have identified 12 genetic factors that increase the risk for NSCL/P in Europeans. Six of them have been independently replicated in samples derived from the same population. The aim of the present study was to replicate the remaining six NSCL/P risk loci in chromosomal regions 1p22.1, 1p36, 3p11.1, 8q21.3, 15q22.2, and 20q12 in a family-based sample of European descent. Each of the top-associated SNPs (single nucleotide polymorphisms) was genotyped in 343 NSCL/P and 266 NSCPO nuclear trios. Single-marker association analysis in the NSCL/P sample showed a significant association with SNP rs742071 (1p36, Pcorrected = 3.74 × 10−3), which is located in the intronic region of PAX7, a gene known to be functionally implicated in craniofacial development. Two additional loci, 1p22.1 and 20q12, were nominally significant, but did not withstand correction for multiple testing. There was no evidence that the NSCL/P risk alleles contribute to the etiology of NSCPO, further supporting that these two subtypes of orofacial clefting are primarily etiologically distinct. © 2013 Wiley Periodicals, Inc.