Inherited polygenic effects on common hematological traits influence clonal selection on JAK2^V617F and the development of myeloproliferative neoplasms.

ABSTRACT: Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2^V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2^V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2^V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2^V617F carriers, making them two to three times less likely to have essential thrombocythemia than c

SUBMITTER: Guo J 

PROVIDER: S-EPMC10864174 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature