The associated SNPs were in an ‘LD block’ that included two genes, spondin 2 (SPON2) and ring finger protein 212 (RNF212). The authors suggested that RNF212 is an excellent candidate for a human recombination gene because it is homologous to a gene involved in recombination in yeast, although further studies are required to determine which SNP and which gene influence recombination rates as well as the exact mechanism for the sex-specific effect. Nonetheless, these results illustrate a genotype-sex interaction of alleles with additive and opposite effects in males and females (Figure 2, Panel C). Loci with this type of genotype–sex interaction effects would never be detected in a genome-wide association study in a combined sample of men and women, where the opposite nature of the association in the two sexes would cancel out any observable effect in combined samples, similar to other genotype–environment interactions54,82-84.
