Please forgive grammar issues and any spots where I don’t complete a thought or I repeat myself. I’m tired, but I need to get this off my mind. Today, I was reading my google generated news stream on genetics when I ran across an article on MIT’s Technology Review website. It was so outright misleading, that my mind has been ruminating on it ever since. Here is my vent. In all honesty, I have a love hate relationship with 23andme. They were the first DNA test I did before I got deeply into Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS). 23andme relies on genotyping which is not nearly as good or broad as WES or WGS. 23andme clearly points out to consumers that there is an error ratio and they tell customers to retest anything that comes up positive. For someone who is ill and on a budget and who understands 23andme is not perfect and any results should be retested is going in with their eyes wide open. I’ve had a few positive results come up on 23andme (before I did WGS). I posted somewhere about my experience and how when there are a large number spots tested (think 100,000+) and there is an error ration of maybe 2%, there will be several that come up falsely as variants when they shouldn’t be (false positives). Some of those false positives will be on locations where variants are rare. Therefore, for people like me who do computer runs filtering for pathogenic mutations with low population frequencies, it will appear that 23andme’s error ration is much higher than it really is due to the fact that severely deleterious pathogenic mutations appear rarely (otherwise the human population would be wiped out). This is why all people should re-test any deleterious mutations that they are worried about with low population frequencies. However, read carefully the link address on today’s article by MIT’s Technology Review is https://www.technologyreview.com/th...sults-from-consumer-dna-tests-might-be-bogus/ Yes, you read that right. “Up to 40% of results from consumer DNA tests might be bogus.” There is so much there that is wrong. First, the original research article that appeared in the journal Nature at https://www.nature.com/articles/gim201838 was written and authored by Ambry Genetics, a competitor to 23andme in the respect that they are a clinical medical grade lab and not direct to consumer. They also get a lot of money from redoing genetic tests done by 23andme and other direct to consumer companies. Since they have their hand in the pot (make money based on the issue in this article), Nature and MIT should have been very careful in reviewing the information for misleading and wrong information. I agree in part with their “Conclusion” that “Our results demonstrate the importance of confirming DTC (Direct to Consumer) raw data variants in a clinical laboratory that is well versed in both complex variant detection and classification.” Not all raw data variants are pathogenic or deleterious, therefore not all variants need to be confirmed with a clinical lab - that's a spot where they should have chosen their words more carefully. 23andme themselves tells people to retest their results in clinical labs. Where the authors move from poorly chosen words to outright negligence (and where I believe 23andme has potential legal recourse) is with this line. “Results: Our analyses indicated that 40% of variants in a variety of genes reported in DTC raw data were false positives.” Of the three deleterious results from 23andme that I initially had retested with medical labs, one of them was confirmed to be a false positive. That’s a 33% error rate. However, when running my 23andme results against my WGS done from a clinical lab, the error rate in much much lower when looking at all variants and not just filtering for rare deleterious pathogenic mutations. As I mentioned above, the error rate looks much higher when pulling out variants that are deleterious and that are rare (low in population). In addition, two of the variants called by 23andme correctly had rs#’s (SNPs). The third one was hidden behind a 23andme internal number (i#). When using internal number with positions, 23andme tells consumers that those especially cannot be relied upon. There are many things that I would like to see 23andme change. However, they are in a good price point for budget conscious individuals. They clearly tell everyone that they have an error rate. So then what did MIT pick up when reading this biased research article and then report? The title on the MIT site is “Up to 40 percent of DNA results from consumer genetic tests might be bogus.” It is accompanied by a picture of 23andMe’s test kit. https://www.technologyreview.com/th...sults-from-consumer-dna-tests-might-be-bogus/ No, not up to 40% of DNA results from consumer genetic tests might be bogus. No, it’s much lower than that. It’s when one sorts for rare pathogenic variants, that the errors are picked up in higher numbers. That doesn’t mean that if someone is looking at all their results from 23andme on the BRCA1 gene (which might have many breast cancer causing mutations) that 40% of those mutations are potentially wrong. 23andme tested 24 positions for me on the BRCA1 gene. No issues came up. The negligent article would make someone not familiar with the issue think that 40% of my results are wrong. So then that would mean that there is a good chance that some of the breast cancer causing mutations that 23andme said I don’t have, I actually may have. Nope. WGS found that I have 124 variants on BRCA1, but not one of them is pathogenic or deleterious or even potentially troublesome (ex. missense with low population frequency). For the 24 positions tested by 23andme, the WGS test came up with the same results. Therefore 0% error ratio for me on BRCA1 for 23andme. Comparing my WGS with 23andme, the error rate is very low overall. It only looks high when looking at rare deleterious pathogenic mutations. Do you know what’s going to happen next? The news industry is going to pick up on this very false headline and run with it. For all I know I could be in that Ambry research of 49 patients. One of the 3 positive 23andme tests that my doctor initially retested with a lab – was done with Ambry Genetics and they found that variant was false. So yes, I could be in that sample. Yet while 33% of the initial tests on me that were sent out to be confirmed by outside labs were false, that does not mean 23andme has a 33% error ratio. It all comes down to the filtering down the variants for unusual and troublesome ones. I hope 23andme fights off this attack. The DTC tests need the media to be educating people about the pros and cons of tests and what to expect, but to blatantly say there is a 40% error ratio is completely false and is just being used to scare people. Ambry Genetics should be ashamed at using this type of self-promotion and spreading false information. They could have presented the subject in a truthful manner which would still back up the position to retest all concerning mutations -- but they chose not to. And then the journal Nature and MIT’s Technology Review decided to give this error wings. Shame on them for not doing their research.