PathWise is a clinical decision-support and communication tool. It does not diagnose disease, alter clinical thresholds, or replace guideline-based care.
The underlying polygenic risk scores (PRS) used by PathWise are drawn from published models with documented validation characteristics. The pathway-level interpretation is an added explanatory layer designed to improve patient understanding, prioritization, and engagement.
Pragmatic studies are underway to evaluate its impact on real-world outcomes.
A traditional PRS aggregates multiple variants into a single risk number. PathWise takes that same validated signal and organizes it into biologically coherent pathways. This allows clinicians to explain how risk is distributed across systems rather than discussing a single abstract score. Risk estimation is not modified. Interpretability is.
PathWise does not introduce new guidelines, targets, or treatment thresholds, but It does change the way you approach your patient. It supports how clinicians explain prevention, counseling, and monitoring, particularly when patients ask why specific lifestyle or monitoring recommendations matter for them personally.
PathWise differs in four important ways:
Patients do not receive standalone recommendations without clinical context.
PathWise uses PRS models with published performance characteristics and is intended to be interpreted alongside clinical context, family history, and environmental factors. It is not designed to be used in isolation or as a sole basis for decision-making.
Ongoing evaluation includes patient understanding, engagement, and interpretation across diverse populations, with attention to known limitations of PRS performance across ancestry groups.
No. PathWise explicitly avoids deterministic language. Genetic risk is framed as modifiable biology, emphasizing that many risk signals reflect sensitivity to lifestyle, monitoring, and preventive care rather than inevitability.
Results are intended to be reviewed in a clinician-guided context, alongside family history, clinical markers, and patient preferences. Ongoing evaluation includes patient response, comprehension, and emotional impact across diverse populations.
Yes. Complex traits are influenced by many genes.
Pathways are used as a clinically meaningful abstraction layer. They organize genomic complexity into biologically coherent systems grounded in known physiology, making the information usable in real clinical conversations, prioritizing interpretability over exhaustiveness.
A polygenic risk score aggregates the effects of many common genetic variants, each with small effect size, to estimate inherited susceptibility to a disease or trait.
PRS are:
Validated PRS have been shown to:
PRS is increasingly discussed in:
While total PRS is useful, it presents challenges in clinical conversations:
This is often where translation into actionable counseling becomes difficult.
PathWise builds on validated total PRS by organizing genetic variants into biologically coherent pathways relevant to disease mechanisms.
Instead of asking only: How high is this patient’s inherited risk? PathWise also explores which biological processes may be contributing most to that risk.
Examples of pathway groupings include:
PathWise PRS is:
PathWise PRS is not:
“The overall score estimates inherited risk. The pathway view helps us explain why certain prevention strategies may matter more for you.”
Patient Talking Points:
For clinicians, pathway context can:
Clinical decisions remain guideline-driven. PathWise informs how to frame and emphasize care, not what care to provide.
This reflects a common evolution in medicine: validated risk assessment followed by interpretive clinical tools, with ongoing outcome validation.
General PRS:
Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet. 2018;19:581–590.
Lewis CM, Vassos E. Prospects for using polygenic risk scores in clinical care. Genome Medicine. 2020;12:44.
Khera AV, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50:1219–1224.
PRS in Cardiovascular and Metabolic Disease:
Inouye M, et al. Genomic risk prediction of coronary artery disease in nearly 500,000 adults. J Am Coll Cardiol. 2018;72:1883–1893.
Knowles JW, Ashley EA. Cardiovascular disease: The rise of the genetic risk score. PLoS Med. 2018;15:e1002546.
Pathway- and Biology-Informed Interpretation:
Gusev A, et al. Partitioning heritability of regulatory and cell-type–specific variants across traits. Nat Genet. 2014;46:922–928.
Pers TH, et al. Biological interpretation of genome-wide association studies using predicted gene functions. Nat Commun. 2015;6:5890.
Boyle EA, Li YI, Pritchard JK.An expanded view of complex traits: omnigenic model. Cell. 2017;169:1177–1186.
