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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
The predictive capacity of personal genome sequencing
Nicholas J Roberts1, Joshua T Vogelstein, Giovanni Parmigiani
1Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
Science Translational Medicine
|April 5, 2012
Summary
Whole-genome sequencing can identify genetic risk for common diseases, but most negative results offer limited information. While most individuals may not show high risk, some could be alerted to significant predispositions.
Area of Science:
- Genomics
- Medical Genetics
- Disease Prediction
Background:
- Advancements in DNA sequencing enable comprehensive germline variant identification.
- The predictive power of whole-genome sequencing for common diseases in the general population remains unclear.
Purpose of the Study:
- To estimate the maximum capacity of whole-genome sequencing in identifying individuals at clinically significant risk for 24 common diseases.
- To assess the informativeness of negative genetic test results.
Main Methods:
- Utilized the 'genometype' concept to define genetic risk levels for specific diseases.
- Analyzed data from numerous monozygotic twin pairs, who share identical genetic risk factors.
- Estimated predictive capacity based on shared genometypes within twin pairs.
Main Results:
- For 23 out of 24 diseases, the majority of individuals are predicted to receive negative test results.
- Negative results are often uninformative, with risks for 19 diseases remaining 50-80% of the general population risk.
- In optimal scenarios, over 90% of individuals could be alerted to a significant predisposition for at least one disease.
Conclusions:
- Whole-genome sequencing has limitations in predicting common disease risk for the majority of individuals.
- The clinical utility and interpretation of negative genetic test results require careful consideration.
- Findings impact the valuation and application of genetic testing across healthcare and policy sectors.
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