Integrated genome-wide analysis of expression quantitative trait loci aids interpretation of genomic association studies


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.

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Natural Variation in Gene Expression Modulates the Severity of Mutant Phenotypes


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.

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