1.07, 1.22 and 2.85 respectively. Taking these arguments to their logical conclusion, our data are also consistent with the possibility that 274 SNPs each with an OR = 1.22, r 2 = 0.8 and MAF = 0.2 lie undetected in the human genome, with 20% probability. The total contribution of these SNPs to λS would be 10, consistent with observed estimates [30]. This calculation must be viewed as hyper-conservative in terms of the contribution of common variation since it assumes that all contributed variants have an equal relative risk, while observations from other conditions make clear that effect sizes fall off after the first several that are discovered [31]. We also note that the pattern of reduction in λR moving from first to second to third degree relatives is more consistent with the presence of epistatic relationships among causal SNPs, rather than the independent model considered here [32].
