In light of our findings, we found their results intriguing: an increasing heritability associated with MAF is appealing because the contribution to heritability of any SNP of frequency p is 2p(1-p)a2, where the SNP’s effect a can be assumed to be roughly equal over all SNPs under the infinitesimal model; on the other hand, it seems unlikely that low MAF SNPs have no contribution to heritability because there are so many of them in the human genome (Table S9). Our results from Sweden argue that these low MAF SNPs do contribute to OCD heritability, their contribution is roughly in proportion to the frequency spectrum of alleles, and can be assumed to be of similar effect (i.e., a) across the frequency spectrum. Thus, our results show that future studies of less common and even rare alleles are also informative for OCD etiology, with the caveat that effects of risk alleles of very low frequency can be difficult to detect by case-control methods.
