Transmission of rare variants in parent-offspring trios – power or no power?

My untested assumption. Recently, I have boasted quite a bit about the power of the trio design, i.e. the inclusion of patients and parents in the analysis of rare genetic variants. Rare variants, in contrast to monogenic variants that arise de novo, are usually transmitted from unaffected parents and are the big unknown of modern day genetic studies. Much of the missing heritability may be accounted for by rare variants, but identifying these variants from genomic noise is difficult. Power calculations for association studies usually suggest that thousands, if not tens of thousands, of patients are necessary to identify these variants with sufficient statistical certainty, a sample size that the field of epilepsy research may never arrive at. So what about switching to parent-offspring trios? Would this help us? Follow me on a brief statistical journey through the land of rare variants. Continue reading