How we estimate risk
Our calculations of your estimated lifetime risk for each condition are based on:
The average lifetime risk that a person of your gender will have that condition.
This is compiled from authoritative epidemiological reports in the medical literature. The figures are based on the total lifetime risk for that condition, typically for a U.S. population and for your gender. The risk for some rare conditions is difficult to know with certainty and is estimated from the best available published evidence, using information about the incidence of the condition and the population age distribution in the United States.
Which risk markers we found when we scanned your genome.
These risk markers meet our criteria for reliability and significance. The tested markers are listed within your report for each condition. For each condition, we test your DNA sample for one or more SNPs (single nucleotide polymorphisms) that have been shown to be associated with the condition. We select these SNPs based on the strength and reproducibility of the evidence reported in the scientific literature. (If you want to read this literature, we provide the citation for each marker we use.)
How much your risk markers increase your odds of having the condition, compared to someone with no markers.
These "odds ratios" are based on the original studies that identified these markers as being associated with disease risk. From the scientific literature, we have obtained the odds ratio showing the increase in the risk of a condition among subjects who had one or two copies of the risk marker at each SNP location. The odds ratio depends on the number of copies of the risk marker. Some studies only report the odds ratio for a single marker, and in those cases we make some assumptions to calculate the odds ratio for two markers.
A model for visualizing, ranking and estimating lifetime risk by combining genetic risks when we test for more than one marker for a condition.
We use a "multiplicative" model for combining the odds ratios from each marker in our scan. To estimate the combined effect on a person's risk, we have applied a formula that takes into account the lifetime risk of that condition and the prevalence of each marker within a reference population; converts the odds ratio to a relative risk; and finally multiplies the risks together. This multiplicative model is one of several available for combining risks. We also compare you to a reference population, the International HapMap Project, which is the largest publicly available database of people with Northern and Western European ancestry. As additional reference population databases become available we will update this information, and you may find the lifetime risk numbers become more precise based on different ethnicities. To determine your estimated lifetime risk, we take into account the lifetime risk of the condition and the average score in the reference population. This formula assumes that marker frequencies in the reference population are representative of your own ancestry, that each marker has an independent effect on your overall risk and that the distributions of the marker versions in the general population are independent.
The result is an estimate of your lifetime risk for that condition, based on the markers we found in your genome, which you can then compare against the average risk for that condition.
It is an estimate because the above assumptions, while reasonable, may not always be true. We also tell you where your risk factors rank, compared to the rest of the population.
