The answer is simple: You won’t.
As research evolves, learning SNP by SNP will become impossible and unnecessary.
Paradoxically, the growing complexity of genotype-phenotype relationships will simplify your learning. As you consider or navigate genetic assessment in practice, it helps to acknowledge two types of complexity.
- Polygenic traits
Genetic variations seldom act alone in determining a physiological feature. In fact, 23andMe inspects 762 different genetic variants to determine your genetic weight , and 1,244 variants in their diabetes risk assessment . Weight and diabetes risk are just two examples of a long list of polygenic traits, which include vitamin D levels, drug metabolism and other clinically relevant phenotypes (Figure 1). In the future, polygenic risk scores will incorporate all of the known loci in to determine genetic risks and predispositions.
2. Pleiotropic variants
On the other hand, a single variant may impart multiple phenotypes. For example, the clinical manifestation of the COMT rs4680 Val/Val variant includes at least 3 different traits (Figure 2). COMT rs4680 is a pleiotropic variant, in which a single loci modifies multiple traits.
Feeling confused? If you’re a clinician, your part should be simple.
Read a genetic report without analyzing it. The company should have already analyzed and interpreted the patient’s SNPs for you.
You wouldn’t spend precious time learning about the scientific process behind a CBC or comprehensive metabolic panel. Likewise, if you trust the company’s process and expertise, there’s no need for an exhaustive audit of their scientific method. You might even jump to false conclusions because of your lack of knowledge in the area.
If you trust your genetic testing company (and any 3rd party interpretation apps or services), you can sit back, relax and just read the report, which should clearly explain what each result means. A good report will not leave you with the temptation to between the lines or search PubMed to find “the real meaning” of a SNP.
When choosing a service:
- Take a moment to request research abstracts from each company that substantiate each of their genotype-phenotype algorithms.
- Spot check the science by entering the rsID of the variant and the company’s phenotypic association (e.g. vitamin B12) in Google Scholar
- Take advantage of any free learning resources for clinicians.
Genetics may be complex, but learning doesn’t have to be.
Illustrations created with BioRender.com.