Genes-R-Us — Interpreting your risk

Posted: Wednesday, November 2, 2011 5:02 pm

You sent your saliva sample off to be analyzed by your favorite Direct-to-Consumer (DTC) genetic testing company. You open the e-mail which announces, “Your DNA results are in.” Now what do you do? 
Your results are only available on-line, so you will need a computer. Forget about receiving a hard copy of your report in snail mail. Your results are extended as new scientific papers are published and reviewed. This kind of frequent updating is inconsistent with the ink-on-paper approach to information dissemination. On average, I get updates about once a month.
You login in to your DTC genetic testing account and bravely click the hot link for disease risk. You see over 100 diseases as you scroll down the page. There are a few particularly unpleasant ones: Alzheimer’s, Parkinson’s and breast or prostate cancer at the very top of the page with little locks on them. You must electronically agree that you really do want to know your risk for these “locked” diseases, presumably after you have read the warnings.  
These diseases are “locked” because certain SNPs (i.e., single DNA “letters” that vary between people), will increase your change of developing the disease more than environmental factors. Yes, they are polygenic diseases (many genes impact their development), but genetics appears to outweigh the environment. Bluntly speaking, you may not be able to mitigate your risk by modifying your behavior.   
If you scroll below the locked list, three numbers appear for each disease: (1) your risk (2) average risk and (3) your risk compared to the average. A good DTC genetic testing company will also provide you with a (4) measure of confidence for the three risk numbers. I have 27 diseases with an elevated risk, 26 with a lower risk and 58 with a typical or mixed result. 
Let’s work through an example. 
Age-related macular degeneration (AMD) is the leading cause of blindness in people over 60 in the U.S. GenomeWide Association Studies (GWAS) have found that three SNPs are associated with an increased risk for Caucasians to develop AMD. That is pretty amazing when you think about it — three little letters out of more than three billion. These findings have been replicated independently using different study participants, so the “measure of confidence” is high for the calculated risks associated with AMD.
Now about those “risky” numbers … Suppose that “your risk” of AMD is reported to be a 26.6 percent. This means that based on multiple GWAS, 266 out of 1,000 people having the exact same three SNPs as you are estimated to develop AMD in their lifetime. Your SNPs are referred to as your genotype. So another way to specify “your risk” is that individuals with your genotype have a 26.6 percent risk, or have about 1-to-3 odds, of developing AMD. (26.6-to-74.4 is roughly 1-to-3.) 
But how many people actually develop AMD in the U.S.? The “average risk” over every possible genotype is estimated to be 7 percent or 7 out of 100 people.  That makes “your risk compared to the average” 3.79 times higher (3.79 results from 26.6 divided by 7). That number incorporates your risk compared to how frequently the disease occurs. 
A decreased risk for a given disease implies that one’s genotype decreases the risk of developing that particular disease compare to the average person. But remember protective genotypes for polygenic diseases do not come with warranties.
About those AMD risk numbers … they are mine. (Are you glad that you are not me?) Am I doomed to develop AMD? No. AMD is a nasty brew of genetic and environmental factors. Does it mean I need to take my risk seriously? Absolutely. My birth mother’s genotype is only half my AMD risk and she developed AMD. But she smoked like a chimney, did not invest in good sunglasses and lived in sunny Southern California.  
Disease risk is very important to understand. Interpret your risk properly, but do not over interpret it. For most diseases, your genome is not the whole story. Do not be afraid to read your book. Knowledge can be power. The movement to take away the “direct-to-consumer” part of genetic testing is based on the assumption that you are not able to understand your risk. I beg to differ.
Editor’s note: Nancy Miller Latimer has worked in scientific research and development for 27 years. She blogs at neuronalbeauty.blogspot.com. Published in The Messenger 11.2.11