How much can personal genomics companies tell you about your health?
Author: Kate Hodgson
Artist: Bella Marwick
Editor: Helen Wu
DNA: It is what makes you, you! Variations in our DNA sequences drive diversity amongst the human species. Geneticists work to discover which genetic variants connect to particular observable characteristics, focusing on variants linked to health conditions and diseases. Have you ever wondered what your unique DNA sequence can tell you? Personal genomics companies such as 23andMe allow consumers to have their DNA sequenced and analysed for variations associated with traits or conditions by simply sending in a saliva sample. These traits can vary from the trivial, such as your likelihood of disliking cilantro, to the more consequential, such as those associated with cancer development.
According to the National Human Genome Research Institute, the cost to sequence the entire human genome has decreased exponentially over the past two decades, from $100 million in 2001 to approximately $1000 in 2022. This decrease in cost coincides with the emergence of revolutionary sequencing technologies. Next-generation sequencing was introduced for commercial use in 2005, enabling the sequencing of multiple DNA strands simultaneously which made DNA sequencing faster and more efficient compared with its predecessor, Sanger sequencing. With a quicker and more accessible way to sequence DNA, 23andMe pioneered direct-to-consumer genome testing in 2006. 23andMe launched by offering an ancestry service that claimed to show the locational origins of the consumer’s DNA. A subsequent service emerged, capable of informing consumers about their predisposition for health-associated traits. Since its beginnings in 2006, 23andMe has sold an immense 12 million DNA kits, demonstrating the popularity of direct-to-consumer genome testing with the general public. In theory, test results from these personal genomics companies could help people prepare for their future by providing knowledge about variations in their DNA sequence that could influence their health. Sounds promising, right? The reality is that there are many problems with this kind of personal DNA testing, particularly in how the sequencing data is analysed and correlated to the traits of interest.
A common kind of genetic variant sought out by personal genomics companies is called single nucleotide polymorphisms (SNPs). SNPs are locations at which single bases in the genome vary between individuals, resulting in different versions of the same gene. Genome-wide association studies (GWAS) is a method used to correlate SNPs with particular traits. This method compares the entire genome sequences of people affected and unaffected by a trait of interest and searches for the more abundant SNPs in affected individuals. GWAS, however, is not a flawless investigative tool. A major pitfall of GWAS is that it might detect variations that only have minimal effects on the trait when acting alone and instead have an additive effect in tandem with many other variants. Moreover, as GWAS is a correlational method, it is limited by the number and range of subjects used. Rarer variants associated with a trait will need a substantial number of study candidates to be detected.
In addition to the issues with variant-trait association methods, the search for trait-associated variants in the consumer’s genome by personal genomics companies is, at best, superficial. Take the example of hereditary prostate cancer. 23andMe claims to estimate the relative risk of developing the disease but only searches for one variant in one gene correlated to an increased risk of prostate cancer. The target in question is the G84E variant in the HOXB13 gene. Nonetheless, the development of prostate cancer has been linked to more than 150 SNPs, and these variants extend beyond just the HOXB13 gene. The G84E variant is also only typically found in people of European descent, so the relevance of a negative test result to somebody of non-European descent is negligible. It is an oversimplification to base the risk of developing conditions as complex as prostate cancer by searching for a singular variant when many more are implicated.
Consumers of personal genomics tests should exercise caution when interpreting their results, especially those indicating potential health risks. The complexity of personal genomics, particularly the intricate impact of genetic variations on observable traits, underscores the need for careful consideration. Importantly, the data analysis methods employed to correlate these variants with traits, as well as the techniques utilised to forecast the risk of developing health conditions or diseases, are fraught with oversimplifications. The Food and Drug Administration substantiates this caution, advising that “results obtained from the tests should not be used for diagnosis or to inform treatment decisions.”
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