The unreliability of SNP chip based genetic testing

[Hoopoe]

Genetic testing can be performed with a device called SNP chip. Not all genetic testing is done with these. Direct-to-consumer genetic testing companies like 23andME often use SNP chips. A problem with SNP chips is that they are unreliable when it comes to rare gene variants. There is the risk that patients like us, who are interested in an explanation for their health problems, could be misled by a false positive rare gene variant. Rare gene variants are more likely to be pathogenic than common ones. A false positive rare variant might look like a credible explanation for a person's ME/CFS if it happens to be associated with a disease that has some similarity to ME/CFS.

This article says

Overall, genotyping using SNP chips performed well compared with sequencing; sensitivity, specificity, positive predictive value, and negative predictive value were all above 99% for 108 574 common variants directly genotyped on the SNP chips and sequenced in the UK Biobank. However, the likelihood of a true positive result decreased dramatically with decreasing variant frequency; for variants that are very rare in the population, with a frequency below 0.001% in UK Biobank, the positive predictive value was very low and only 16% of 4757 heterozygous genotypes from the SNP chips were confirmed with sequencing data.

SNP chips are extremely unreliable for genotyping very rare pathogenic variants and should not be used to guide health decisions without validation.

https://www.bmj.com/content/372/bmj.n214

This seems like good advice.