BMP2 and craniosynostosis: These findings implicate a two locus model of inheritance in non-syndromic midline craniosynostosis via epistatic interactions of rare heterozygous SMAD6 mutations and common risk alleles near BMP2. There is extremely strong evidence implicating each locus independently, along with highly significant evidence from both analysis of association and linkage that the risk of craniosynostosis is markedly increased in individuals carrying risk alleles at both loci compared to those with only a single risk allele at either locus.