Germline genetic variation within the protein-coding region of IFNL4 affects MR during IFN-α treatment of PV. (A) Genomic organization of the IFNL locus on human chromosome 19q13.2. (B) An association plot derived from GWAS performed for MR after a 12-month follow-up of ropeg treatment (n = 102 patients). The plot is representative of all GWAS performed on both HR and MR data after a 12-, 18-, 24-, 30-, and 36-month follow-up. (C) Longitudinal P values for the association of the IFNL4 tagSNP rs12979860 with response to ropeg over a 36-month follow-up (FU). (D) Fraction (%) of MRs in the 3 main functional categories: patients who produced no functional IFNL4 (no IFNL4), those who produced impaired IFNL4-S70 (IFNL4-S70 alone+IFNL4-S70/P70), and those who produced fully functional IFNL4-P70 alone. Numbers within the bars represent total patients in the categories. (E) JAK2V617F mutant allele burden changes (absolute change from baseline value) at a 36-month follow-up in patients stratified according to IFNL4 diploid functional status. N, no IFNL4; S, IFNL4-S70; P, IFNL4-P70.