CRLF3 regulates platelet traits in humans and is a therapeutic target for ET. (A) Locuszoom of CRLF3 (left) and STK38 (right) showing variants associated with platelet distribution width (PDW) and mean platelet volume, respectively. The conditionally independent variant is indicated by a purple diamond; linkage disequilibrium (LD) values (r²) with this variant are indicated by dot colors according to the legend. The CRLF3 locuszoom plot shows the conditionally independent variant (rs6505211: −log10P, 27.1; MAF, 17.6%) is in high LD with a number of variants, which are significantly associated with PDW. In the case of STK38, the locuszoom plot indicates that the conditionally independent variant (rs141301223: −log10P, 10.4; MAF, 0.041%) is not in high LD with nearby variants (common for rare variant associations). (B) Platelet counts from young (≤20 weeks) and old (≥48 weeks) female WT control (blue; n = 6 young and 5 old), Crlf3^−/− (red; n = 7 young and 7 old), JAK2 V617F ET (purple; n = 7 young and 9 old), and Crlf3^−/− JAK2 V617F (green; n = 6 young and 6 old) mice. (C) Fixed tibia sections stained with Gömöri reticulin silver stain and imaged by light microscopy at 20× magnification. Images are representative of 3 mice per genotype. Data represent means ± standard deviations. Two-way analysis of variance with correction for multiple comparisons using the Holm-Sidak method. ***P < .005. ns, not significant.