Imputation in genetics refers to statistical inference from unobserved genotypes (not extracted in laboratory analysis). And you may wonder, how is it possible to infer the genotype of a variant that has not been analyzed? What is the accuracy of this?
Genetic imputation is possible thanks to what is known as linkage disequilibrium (LD). When we inherit genetic variants from our parents, we do it in "blocks" as some genes do not segregate independently. This means that they are inherited together more than expected.
This occurs to preserve the DNA building blocks that often have similar and vital functions so that they always go together.
For example, if there is a very high linkage disequilibrium for variants 1 and 23, knowing only the "letters" (alleles) of one of the variants, by statistical inference we can infer the alleles of the other variant, since having a very high LD, in most cases, they are inherited together.
Thanks to this phenomenon that occurs in nature, if for example we have analyzed the AA genotype for variant 1, although we have not analyzed variant 23, we can infer by imputation which alleles you will have at that position in the genome.
This is done with specialized genetic algorithms and databases that contain 100% of the genomic information for a large number of individuals giving the imputation a high statistical value.
Reliability and accuracy of genetic imputation
There is a lot of study, work and effort behind LD and the imputation, giving it extremely high reliability. Such is the confidence in this technology that most research work related to genetic variants uses genetic imputation.
The genetic imputation presents a large number of internal quality controls making this inference extremely reliable (more than 95%), approaching the results obtained in whole genome sequencing, but with a much lower cost.
In ADNTRO we use very powerful databases and imputation algorithms that allow us to have a reliability of more than 95%. However, since it is not an inference with 100% reliability and the transparency that characterizes us in ADNTRO, if you have one of the variants that define the APOE haplotype imputed, we want to inform you of it.