You may be one of the more than 30 million people that have used genetic testing companies to learn more about your ancestry, health, or even genetic risk factors. These DNA test results generally include a raw DNA file that can be uploaded to other sites to learn additional information from your genes. Promethease is one of these sites that accepts a DNA file upload and provides a comprehensive report of genetic risk factors for various medical conditions. Here at Genomelink, we have gained extensive knowledge and expertise from years of working in the genetic testing industry. In this blog post, we will be using this expertise to help you navigate your Promethease report to identify your genetic variants associated with celiac disease (or coeliac disease, in European countries).
An Introduction to Your Promethease Report
Promethease is a third-party DNA testing service that provides detailed health reports on your risk of developing certain diseases based on your genetic profile. Their reporting uses SNPedia, a website that collects research on genetic variants that put a person at high risk for certain diseases. This data is based on locations in your genome called single nucleotide polymorphisms (SNPs), where there tend to be genetic differences in the human genome. Each DNA testing company reviews specific SNPs within your genome to provide their results, rather than looking at all 3 billion bases that make up a person’s whole genetic profile.
The raw data that is uploaded to Promethease only includes the data from the SNPs tested by the original company. In other words, your results are based on specific regions of your DNA rather than the entirety of your genetic profile.
Promethease accepts data uploads from several testing companies, including:
Understanding Your Genetic Risk for Celiac Disease in Promethease
Celiac disease is an autoimmune condition that leads to gluten intolerance in those affected. Gluten is a protein found in wheat that, when eaten by a person with this autoimmune disorder, causes an immune response in the small intestine. This reaction creates symptoms similar to irritable bowel syndrome (IBS), such as stomach pain, changes in bowel habits, and weight loss. It has been a growing concern around the world as gluten sensitivity and gluten-free diets have grown in popularity.
The exact causes of celiac disease are not entirely understood, but we know that it’s a combination of genetics and environmental factors at play. Researchers have identified some genetic markers associated with a higher risk of developing the condition, and that’s what we’ll be looking into today.
Before that, a quick review of a genetic concept: Every gene has different variations that can be inherited from your parents, called alleles, and each person gets one allele from their mother and one from their father.
Not all celiac genes have been identified, but one gene associated with the disease is the human leukocyte antigen (HLA) gene. Some of the common HLA alleles found include HLA-DQA1, HLA-DQB1, HLA-DQ2, HLA-DQ2.2, HLA-DQ2.5, and HLA-DQ8. The primary risk alleles that are associated with celiac disease are HLA-DQ2.2 and the HLA-DQ8 haplotypes.
Your Promethease report estimates your genetic risk for celiac disease by determining which gene variants (ie. alleles) are located on the SNPs available in your raw data file. This information is gathered from relevant published research articles, through SNPedia’s database. SNPedia’s database includes over 100,000 SNPs, of which only a few hundred have been associated with the risk of celiac disease.
There are a few options for navigating your Promethease report to find your genetic variants related to celiac disease:
1. Use the search bar at the top of your report
By typing “celiac” or “celiac disease” in the search field (highlighted in red in the image above), you can find all of the SNPs in your report that mention the condition. It is important to note that not all of these results are actually related to celiac genes, but they at least mention “celiac” in their descriptions.
2. Use the search filter (located to the right of the search bar) to search by medical conditions
Filtering your Promethease results by medical conditions allows you to search your report by certain medical conditions. It is important to know that Promethease uses the American spelling of “celiac” and does not recognize “coeliac.”
3. Use the search filter to search by ClinVar diseases
As demonstrated by the images above, there are two different methods to filter your report by ClinVar findings. The ClinVar setting filters your results based on genetic variants that are clinically associated with certain diseases. ClinVar is a publicly accessible database that is managed by the National Institutes of Health (NIH) and tends to provide more reliable and robust results. You can either use the filter field named “ClinVar Diseases” to search your disease of interest (top image), or you can select the “ClinVar” option at the top of the filter field (bottom image).
4. Use the search filter to search for specific genes
Directly below the “ClinVar Diseases” drop-down menu is a search field labeled “Genes.” Here, you can type a gene of interest to filter your results by a specific gene, such as the HLA variants. This may not be the best method of locating your celiac risk because there are many other genes associated with the disease.
5. Any combination of the above methods.
You can use any combination of the methods listed above to narrow or broaden your search results to best research your celiac genes.
Your Promethease report provides A LOT of genetic information that can be anxiety-inducing and difficult to understand. If you have a family history of gluten intolerance or celiac disease, we recommend consulting with your healthcare provider, a genetic counselor, or geneticist. Celiac disease is not entirely understood and using direct-to-consumer genetic testing may not be the most accurate way to learn about your disease risk. Although Promethease may be a great start, completing a blood test with your doctor can give you a more definitive result.
Alternatively, if you’re simply looking to learn more about what your raw DNA data predisposes you to more generally via Promethease, here’s a simple guide for how to do that.