Extended Data Fig. 4: Germline Correlates of m6A.
From: The landscape of N6-methyladenosine in localized primary prostate cancer
a) The overlap of m6A sites identified in RMVar42 and Cotter et al. 202143 with germline SNPs genotyped as described in Houlahan et al.18. b) The distribution of allele frequencies of the A for SNPs/m6A sites in prostate cancer joint peaks (red) compared to the A for SNPs/m6A sites outside of joint peaks (white). c) The SNP rs2240912 is associated with biochemical recurrence (Q < 0.1; Cox Proportional Hazards model). d) The difference in Conti PRS relative to m6A peak status (PRSPeak - PRSNo Peak) across peaks assessed using Student’s T test (two-sided). e-f) Left: The distribution of P values in associations (two-sided T test) between m6A peak status and Schumacher PRS (e) and PHS290 (f). Right: Volcano plots showing log10 P values versus effect sizes (Δ PRS). g) The association between Conti PRS versus the number of MeTPeak peaks per sample using Spearman’s correlation analysis (two-sided). h-i) Left: distribution of P values in modelling associations between risk SNPs and local m6A peak methylation (h) and spatially-associated m6A peak methylation (i) Right: Volcano plots of P values versus effect sizes from additive linear models (β). Data from linear additive model. j) Histogram of the distance (bps) between the m6A-QTL and associated m6A peak. k) The identification of significant RNA, protein and clinical associations based on tag SNPs and gene pairs of m6A-QTLs. l) RNA and protein associations identified using m6A-QTL tag SNP-gene pairs. The disk sizes and color are indicative of the magnitude and direction of the β values of a linear additive model while the background color indicates the Q value. m-n) The associations of the SNP rs4951018 with SLC45A3 RNA (m) and protein abundance (n). Box plots represent the median (center line) and upper and lower quartiles (box limits), and whiskers extend to the minimum and maximum values within 1.5x the IQR. P values from linear additive model (n = 133). o) Top: tables showing associations between ISUP-associated alleles and ISUP Grade Group. Q values are derived from the global Χ2 test. Bottom: tables showing associations between pairs of alleles.
