Genetic factors contributing to l-carnitine levels in 13 091 human RBCs after storage for 42 days. Genome-wide association studies (GWAS) were performed to determine the genetic underpinnings of end-of-storage l-carnitine levels in 13 091 packed RBC units from the REDS RBC Omics index donor cohort. (A) l-carnitine levels were used as an mQTL to perform a GWAS against 870 000 SNPs from a precision transfusion medicine array. (B) Manhattan plot generated via the l-carnitine mQTL analysis. y-axes indicate significance (−log(p)), with genome-wide adjusted significance thresholds at y = 5 × 10−8. (C) A representative QQ plot for the top SNP from this analysis (y-axis showing significance <10−250) for rs12210538. (D) This SNP coded for a missense mutation on the l-carnitine transporter SCL22A16. (E) Alphaphold predicted structure for SLC22A16 in. (F) The rs1220538 SNP was underrepresented in donors of Asian descent, followed by donors of African descent. (G) Locus zoom for rs272855 SNP (intron variant), mapping on a region on chromosome 5 that codes for SLC22A4/5 carnitine transporters. (H) Alphaphold predicted SLC22A5 structure. (I) The rs272855 SNP was found to be most common in donors of African descent and least common in donors of Asian descent.
