To identify putative novel associations, we then filtered out any variant with LD r2 ≥ 0.2 in any ethnic group with any previous reported variant from GWAS, sequencing, or Exome Chip analyses within ±1Mb for a given blood cell trait. We calculated LD in self-reported European ancestry, AA, and Hispanic/Latino individuals from TOPMed freeze 5b. For European and African LD reference panels, we further restricted to individuals with global ancestry estimate ≥0.8. The global ancestry estimates were derived from local ancestry estimates from RFMix [61] using data from the Human Genome Diversity Project (HGDP) [62] as the reference panel with seven populations, namely Sub-Saharan Africa, Central and South Asia, East Asia, Europe, Native America, Oceania, and West Asia and North Africa (Middle East). Global ancestry for each TOPMed individual is defined as the mean local ancestry across all HGDP SNPs. For replication of novel signals, similar to the approach we adopted for the discovery cohorts, we performed association analysis using EPACTS in each contributing cohort and then meta-analyzed with GWAMA.
