Fig. 6: Proteins associated with malignant melanoma and colorectal cancer.
From: Coding and regulatory variants are associated with serum protein levels and disease
a The melanoma risk allele A (highlighted in bold) for the variant rs910873 is associated with high serum levels of ASIP. The x-axis of the box plot shows the genotypes for the protein-associated SNP, while the y-axis denotes the Box–Cox transformed, age, and sex-adjusted serum protein levels. Box plots indicate median (middle line), 25th, 75th percentile (box), and 5th and 95th percentile (whiskers). The P-value (two-sided) shown at the top of the plot is from linear regression analysis. b Scatterplot for the ASIP protein supported as having a causal effect on malignant melanoma in a two-sample MR analysis. The figure demonstrates the estimated effects of the respective genetic instruments on the serum ASIP levels in AGES-RS (x-axis) and risk of melanoma in GWAS by UK biobank data (UKB-b-12915)67 (y-axis), that included 3598 melanoma cases and 459,335 controls. Each center data point displays the estimated effect as beta coefficient = log(odds ratio), along with 95% confidence intervals for the SNP effect on disease (vertical lines) or SNP effect on the protein (horizontal lines). The broken line indicates the inverse variance weighted causal estimate (β = 0.0024, SE = 0.0003, P = 1.1 × 10−17, two-sided), while the dotted line shows the MR-Egger regression (see Supplementary Data 5). c The pQTL rs2241714 is a proxy for colorectal cancer-associated variant rs1800469 (r2 = 0.978) (Supplementary Data 2), located within the gene B9D2 and proximal to TMEM91 which is the reported candidate gene at this locus (see Table 1). The gene encoding TGFB1, a protein linked to rs2241714 in cis, is also nearby. d The variant rs2241714 (and rs1800469) is associated with the serum proteins TGFB1 (in cis), B3GNT8 (in cis), and B3GNT2 (in trans). The P-values (two-sided) shown at the top of each plot are from linear regression analysis. The x-axis of each box plot shows the genotypes for the corresponding protein-associated SNP, while the y-axis denotes the Box–Cox transformed, age, and sex-adjusted serum protein levels. Box plots indicate median (middle line), 25th, 75th percentile (box), and 5th and 95th percentile (whiskers). The chromosomes indicated at the top of each graph correspond to the location of the gene that encodes the protein of interest.
