DNMT3A and cyclic hematopoiesis: Given that two of the most common CH genes (DNMT3A and ASXL1) were not associated with CKD, and that the 380 SNPs only explain 3.6% of the heritability of CH [31], the use of MR in this context is clearly challenging, and may be compounded the possibility of other factors such as horizontal pleiotropy but these concerns are partly mitigated by the large sample size of the GWAS used for CH and CKD.