Population genetics
The patient is well. This domain asks what their genome, and their family history, says about risk, and what an independent physician should do about it: who to test, what to do with a positive result, and how to keep the result from becoming a source of harm.
Why this is a domain
Genomic risk information has arrived in primary care faster than the tools for handling it. Patients bring consumer results, proactive sequencing reports and carrier screens; guidelines say who to refer but not what to do in a practice without a genetic counselor down the hall. The problem is not the test. It is the long tail of decisions that follow: cascade testing of relatives, surveillance schedules that span decades and specialties, polygenic scores whose meaning depends on ancestry and context, and drug-gene pairs that only matter when a prescription is being written.
Independent practice is well placed here. Risk management is longitudinal, and continuity is the thing independent physicians have that the system does not. The five cohorts are five kinds of risk information, each with its own care map.
The five cohorts
| Cohort | Who it covers | Status | Slack |
|---|---|---|---|
| Hereditary cancer risk Who in this family needs testing, and what surveillance follows? | Lynch, BRCA1/2, PALB2 and other cancer syndromes, plus cascade testing | Launch | #cohort-hereditary-cancer |
| Comprehensive genetic risk This healthy adult had a proactive exome or genome. What is actionable, and what is not? | Proactive exome or genome in healthy adults: ACMG secondary findings, FH, inherited cardiomyopathy and arrhythmia | Forming | #cohort-comprehensive-genetic-risk |
| Polygenic risk score Does this score change what we would do for this patient? | PRS for coronary disease, breast and prostate cancer and type 2 diabetes, and how they stack with monogenic results and family history | Seeking a lead | #cohort-polygenic-risk |
| Pharmacogenomic profile When is a pharmacogenomic result worth ordering, and how does it reach the prescription? | Actionable drug-gene results applied to current and future prescribing | Seeking a lead | #cohort-pharmacogenomics |
| Preconception carrier screening What should this couple be offered, and what do we do with a positive? | Expanded carrier screening, preconception counseling and family planning | Seeking a lead | #cohort-carrier-screening |
How the care maps differ here
The Establish year here is about the decision to test and the first result: who meets criteria, which test, what the patient was told before the sample was drawn, and what the report means. The genetics role carries pre-test and post-test counseling, which most primary care practices have never been resourced for, and which the network can supply through the counselor roster.
The Treat year is really a surveillance year: the colonoscopy interval, the breast MRI, the lipid target, the cardiac screen. These are long schedules that outlive any single specialist relationship, which is why the anchor role is primary care. The Sustain year adds the family (cascade testing is where most of the public-health value is, and where most of it is lost5), reclassification of variants, and reassessment as the patient ages into new risk windows.
Behavioral health is on every map in this domain for a specific reason: risk information changes how people see themselves, and an unmanaged result can do more harm than no result.
What the domain needs from the provider rosters
Counselors (genetic counselors above all), esoteric assays (sequencing and reanalysis laboratories with transparent pricing), clinical expertise for variant interpretation, and specialists in oncology, gastroenterology, cardiology and maternal-fetal medicine who accept risk-based referrals from an independent practice.
Starting references
- Miller DT, Lee K, Abul-Husn NS, et al. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023;25(8):100866. doi:10.1016/j.gim.2023.100866
- Lewis CM, Vassos E. Polygenic risk scores: from research tools to clinical instruments. Genome Med. 2020;12(1):44. doi:10.1186/s13073-020-00742-5
- El Rouby N, Johnson JA. Pharmacogenetic testing: evidence, challenges, and pathways to adoption. NEJM Evid. 2025;4(10). doi:10.1056/EVIDra2400343
- Gregg AR, Aarabi M, Klugman S, et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(10):1793-1806. doi:10.1038/s41436-021-01203-z
- Pederson HJ, Narod SA. Why is genetic testing underutilized worldwide? The case for hereditary breast cancer. BJC Rep. 2024;2(1):73. doi:10.1038/s44276-024-00099-x