Single gene disorders that are caused by genetic variants are rare, and finding them can lead to a high probability of disease in an individual and their family. This study aims to determine whether the specificity and sensitivity of SNP chips are effective at detecting rare pathogenic variants.
This retrospective, population-based diagnostic evaluation study included a total of 49,908 people with SNP chop and next-generation sequencing data, along with 21 people who bought consumer genetic tests and shared the data. The primary outcome of the study was genotyping using SNP chips versus sequencing, with results split by the genotype’s frequency.
The findings suggested that genotyping using SNP chips performed well compared with sensitivity, sequencing, specificity, and positive and negative predictive values. All these values were above 99% for 108,574 common variants directly genotyped SNP chips. The findings, however, also showed that the likelihood of a true positive result reduced with a decrease in frequency. For extremely rare variants in the population, the positive predictive value for very low, with only 16% of heterozygous genotypes from the SNP chops confirming with the sequencing data.
The research concluded that SNP chops were not reliable for genotyping very rare pathogenic variants, and hence, should not be used to dictate health decisions.