By [Joehanes and Munson, GB, 2017] Methods Framingham Heart study: 5K samples, whole blood eQTL. QC: polymorphism-in-probe effect is likely minor. Discovery of eQTL: step-wise regression to find independent eQTL. Found 19K independent cis-eQTL and 6K trans-eQTL. Sample size is important for the power: it scales linearly with cis-eQTL, but more with trans-eQTL. Double the size from 2500 to 5000 increase the trans-eQTL by 3-4 fold. Validation of eQTL: (1) Internal: 75% cis and 41% trans-eQTL are validated.
Biological question Mutation in monogenic disease can cause disease phenotype at various level of severity. For instance, cystic fiberosis (CF) is caused by a single gene, CFTR, the homozygous individuals with exactly the same allele $\delta$F508 present a wide range of clinical symptoms. It is due to «modifier genes», MBL2 and TGF-$\beta$. Such observation is general in many Mendelian diseases. Namely, the disease is predictable but the severity of it is highly unknown due to the variation of genetic background.