Even though the SNP heritabilities have wide confidence intervals (from 15%–50%), they provide a critically important constraint on our understanding of the genetics of MD: they indicate that common variants of small effect (with odds ratio less than 1.2, and probably much less) make a large contribution to the genetic susceptibility to the disease, accounting for more than 50% of the heritability. Indeed, the SNP heritability is consistent with the view that the genetic basis of MD consists of many thousands of independently acting loci, each of very small effect, that contribute to disease susceptibility. Before we consider some alternative possibilities, we pursue what this conclusion means for genetic studies of MD. What is needed to find robust, genome-wide significant association? Can we estimate the sample size needed?
