Challenges in Translating GWAS Results to Clinical Care
AbstractClinical genetic testing for Mendelian disorders is standard of care in many cases; however, it is less clear to what extent and in which situations clinical genetic testing may improve preventive efforts, diagnosis and/or prognosis of complex disease. One challenge is that much of the reported research relies on tag single nucleotide polymorphisms (SNPs) to act as proxies for assumed underlying functional variants that are not yet known. Here we use coronary artery disease and melanoma as case studies to evaluate how well reported genetic risk variants tag surrounding variants across population samples in the 1000 Genomes Project Phase 3 data. We performed a simulation study where we randomly assigned a “functional” variant and evaluated how often this simulated functional variant was correctly tagged in diverse population samples. Our results indicate a relatively large error rate when generalizing increased genetic risk of complex disease across diverse population samples, even when generalizing within geographic regions. Our results further highlight the importance of including diverse populations in genome-wide association studies. Future work focused on identifying functional variants will eliminate the need for tag SNPs; however, until functional variants are known, caution should be used in the interpretation of genetic risk for complex disease using tag SNPs. View Full-Text
- Supplementary File 1:
Supplementary (PDF, 2202 KB)
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
Scheinfeldt, L.B.; Schmidlen, T.J.; Gerry, N.P.; Christman, M.F. Challenges in Translating GWAS Results to Clinical Care. Int. J. Mol. Sci. 2016, 17, 1267.
Scheinfeldt LB, Schmidlen TJ, Gerry NP, Christman MF. Challenges in Translating GWAS Results to Clinical Care. International Journal of Molecular Sciences. 2016; 17(8):1267.Chicago/Turabian Style
Scheinfeldt, Laura B.; Schmidlen, Tara J.; Gerry, Norman P.; Christman, Michael F. 2016. "Challenges in Translating GWAS Results to Clinical Care." Int. J. Mol. Sci. 17, no. 8: 1267.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.