Figure 3: Association of the IGHV4-61 locus with RHD susceptibility.

(a) For each variant in the 99% credible set, the common logarithm of the Bayes’ factor is plotted against genomic position. Variants are coloured by linkage disequilibrium with the most associated variant averaged across the entire data set (estimated r²: dark blue, 0–0.2; light blue, 0.2–0.4; green, 0.4–0.6; yellow, 0.6–0.8; red, 0.8–1.0). A vertical blue line indicates the position of the four nonsynonymous variants in IGHV4-61 and locations of expressed IGH gene segments are indicated by blue rectangles below the x axis. (b) Forest plot for the IGHV4-61*02 allele under an additive genetic model with association statistics from LMM analysis in each strata combined by FE meta-analysis. Individual and combined odds ratio estimates with confidence intervals are shown on a logarithmic scale. (c) Structural model of an antibody that includes the IGHV4-61 heavy variable domain (Protein Databank 4FQQ) showing both heavy (blue) and light (white) chains with both the first (CDR-H1, green) and second (CDR-H2, violet) heavy chain complementarity determining loops and the heavy chain interface framework loop (HIFL, red) highlighted. The positions that distinguish IGHV4-61*01 from IGHV4-61*02 are shown as spheres labelled with the amino acids found in IGHV4-61*01.