Health at 23andMe: Anatomy of a 4-Star Disease Risk Report

Type 2 diabetes, prostate cancer, multiple sclerosis — out of the nearly 200 reports 23andMe currently offers covering common and complex diseases, there are at least a few you have heard of. This familiarity is part of the reason why the Disease Risk reports are one of 23andMe’s most talked-about features. But looking at the genetics of a disease — and connecting that information to individuals — is a whole new way of thinking for most people. In this post, I’ll run through the basic nuts and bolts of a 23andMe Disease Risk report.

Each 4-star, or Established Research Disease Risk report contains information about the disease and its biology (located in the “How It Works” tab at the top of the page under the title of the report) and about established associations between genetic variants and disease risk (located in the “Technical Report” tab). The highlight of each report, however, is the individualized estimate of your risk for the condition. This estimate is based on your genetics, information about specific genetic variants that has been scientifically vetted, and publicly available statistics on how common the disease is. You’ll find this risk estimate in the section called the “Odds Calculator” under “Your Genetic Data”:

Want to geek out on the scientific details? Click here for more on how 23andMe calculates your risk.

The example above shows that my risk of developing Type 2 Diabetes over my lifetime (estimated at 79 years) is 26.3%, based on my genetics and information applicable to people with Asian ancestry. The lifetime risk for the average Asian person is 20%, so I am at slightly increased risk based on genetics.

The “Genes vs. Environment” and “What You Can Do” sections. Click to enlarge.

So what can I do with my risk information? Two sections underneath the Odds Calculator are relevant here. One, “Genes vs. Environment”, gives a rough idea of the relative influence of genetic and non-genetic factors for a condition or trait. Type 2 Diabetes, for example, is influenced strongly by non-genetic or environmental factors. So even if your results indicate a relatively higher risk for Type 2 Diabetes based on genetics, there are many environmental factors that influence your risk, and measures one can take to lower that risk. Some of these are listed immediately below “Genes vs. Environment” in the “What You Can Do” section.

The remainder of the report provides more detailed information about individual genetic variants used in the report to calculate a person’s risk. Below “What You Can Do” is a chart called “Marker Effects” (see picture below) showing the relative impact of each genetic variant on risk in the applicable ethnicity.

Mousing over each bar will display the location of that variant in the genome and your genotype — the two DNA letters you received from mom and dad — for that variant, as well as its effect.

For instance, my genotype at the second SNP, called rs1801282 and located in the PPARG gene, is CC. This genotype is associated with the highest odds out of all the genotypes for this SNP in East Asians — but that odds is only 1.04 times higher than average (because most East Asians have the CC genotype). The chart also tells me that most of my individual SNP risks are close to average, but my genotype at one SNP, rs7903146 in the TCF7L2 gene, contributes the most to my overall 1.32 times higher risk for type 2 diabetes. That’s why the red bar is tallest for that SNP.

For more information about each SNP, I can click on the “Technical Report” tab near the top of the page. The Technical Report lists each SNP used in the risk calculations with adjusted odds ratios for for each applicable ethnicity. (If you are sharing genomes with people at the Extended Level, you will also see their results here next to yours.) And for those who just can’t get enough, lists of scientific references used to justify each SNP’s inclusion in the report are provided for further reading.

Keep in mind…

When viewing a Disease Risk report, make sure to take everything in context. An elevated genetic risk is not necessarily cause for concern and a decreased or typical risk is not a reason to adopt unhealthy behavior. Both genetics and non-genetic factors influence our health and risks for diseases and science doesn’t yet know all of these factors or the exact effect of each one in every population. This is true even if we consider only the genetic factors. The handful of genetic variants used to calculate your risk for each Established Research report are only those variants that currently have strong evidence for being risk factors, and often, each variant only contributes a small amount to your risk. 23andMe will update the reports and your risk estimates as our knowledge improves, but they will necessarily remain works in progress.

As such, each genetic risk estimate represents only an approximation of the contribution of your genetics to your risk for disease, based on currently available knowledge. This information can still be very useful — the genetic variants included in the report on Venous Thromboembolism (current customers click here), a clotting disorder, have strong effects on one’s risk and knowledge of that risk could potentially be lifesaving. And simple healthy living goes a long way!

As with all of 23andMe’s Health reports, you are encouraged to contact your personal physician, a genetic counselor, or other medical professional if you are concerned or have questions about your results. 23andMe has partnered with Informed Medical Decisions, Inc., which provides independent genetic counseling services for 23andMe customers.

Current customers can learn more helpful tips and answers to common questions in our FAQ. In the next post, I discuss the reports available under Carrier Status for Inherited Conditions, which are especially relevant for those planning a family.

More Health at 23andMe posts:

Health at 23andMe: What Can You Learn?

Navigating Your Health Results

What’s Your Status?– (Carrier status for Inherited Conditions)

When One Size Doesn’t Fit All – (the genetics of Drug Response)

The Circus of Human Traits

For a refresher course on genetics or help navigating the service, visit Genetics 101 on our website, or see our Frequently Asked Questions.

Check out our companion series, Ancestry at 23andMe, and other articles in 23andMe How-To.

How does 23andMe calculate my risk?

The Odds Calculator takes into account three major components:

  • the effect of genetic variants on risk for the disease,
  • the frequency of different versions of those variants,
  • and the incidence of the disease.

Effects of genetic variants

23andMe’s Disease Risk reports are based on scientific findings linking common genetic variants to disease susceptibility. The association between a SNP and a disease carries with it an estimate of how different versions of the SNP affect one’s risk, a measure usually reported as the “odds ratio”. 23andMe “adjusts” the odds ratios reported in scientific articles so that your risk due to a SNP is always relative to the average in a population.

Population frequency of genetic variants

Each version of a SNP is present at some frequency in a population. These frequencies differ, however, depending on what population you’re looking at. One version may be very common in people with East Asian ancestry, but very rare in people without East Asian ancestry. 23andMe uses this data to determine the “genetic average” and adjusted odds ratios for SNPs in each population.

Incidence of disease in a population

The incidence of a disease is the number of new cases diagnosed in a specific population during a set time period. This information allows 23andMe to provide an estimate of the average person’s risk of developing a disease over a period of time. Disease incidence can also vary from population to population.

The adjusted genotype-specific odds ratios for each SNP used in the report are combined to produce an overall odds ratio for an individual. This combined odds ratio is then used in conjunction with the incidence of the disease to calculate the overall risk of developing the disease based on the individual’s genetics.

For full technical details for 23andMe’s risk calculations, see our white papers on Estimating Genotype-Specific Incidence.

  • anil patwardhan

    curious as to why you do not distinguish between odds ratio and relative risk. most of the snp-disease associations and there effect sizes are drawn from case-control studies in which relative risks can not be calculated. They only approxiamate relative risk for low prevalence diseases.
    in fact most of your risk estimates for complex disease are overestimates …

    • ScottH

      We do make that distinction by showing your risk, based on your genetics, the average risk and how your risk compares to the average. But your point is well taken and we are trying to improve how we communicate an individuals risk for any given disease

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