With many collaborators from TOPMed, the Raffield lab was pleased to contribute to recent whole genome sequencing based publications for red blood cell, white blood cell, and platelet related traits. These publications identified novel single variant signals for these heritable hematological measures, despite the 10x smaller sample size versus existing analyses of imputed genotyped data from the Blood Cell Consortium (up to ~60,000 participants, as opposed to >700,000 participants).
Many of these novel signals were rare/low frequency variants more common in non-European populations. Rare variants in Mendelian genes (such as TUBB1, CD36 for platelet related disorders), including coding variants not annotated as pathogenic in ClinVar at time of publication, and somatically acquired rare variants in genes like TET2 were also identified as contributors to hematological trait variance. These findings highlight the value of sequencing data in diverse population-based studies.