detecting protective SNP and environment effects across all effect sizes. The low risk design, where subjects are ascertained at a low liability, yields power equivalent to a case-control design to detect SNP effects, and much higher power to detect the protective environmental effect. The high-risk design yields power increases similar to case-control sampling with the exception of at smaller SNP effect sizes, where the high-risk design performs better. This is most likely due to an enrichment in SNP effects in high risk families with control offspring. Sampling with a high-risk design from an environmental risk below the mean yields a power profile similar to a case-control design. Sampling high-risk families from below the population mean in environmental risk and low-risk families from above the population mean yields dramatic increases in power across the range of effects to detect both protective SNP and environmental effects.
