Fig. 8: Identification of co-localized caQTLs at MPRA-functional variants.

We performed ATAC-seq on plasma cells from 161 MM patients and scanned the LD regions for lead variant caQTLs using two computational approaches. a In the SMARCD3 region, we detected a significant caQTL around rs78740585, with the minor allele conferring increased accessibility. Consistent with this, rs78740585[T > A] showed a positive MPRA log₂ score and the rs78740585-A risk allele creates an IRF4 site (Supplementary Fig. 4). b In the CDCA7L region, we detected a significant, 1.6 kb wide caQTL around rs4487645, with the major allele conferring increased accessibility. Consistent with this, rs4487645[C > A] showed a negative MPRA log₂ score and the rs4487645-C risk allele creates an IRF4 site. c At CEP120, we detected a significant caQTL covering rs11960493 and eight other variants, including rs62376437 which was borderline-significant in MPRA, suggesting the CEP120 association is enshrined in multiple causal variants. Dashed blue indicates a false discovery rate (−log₁₀ Q value) for Pearson correlation between ATAC-seq signal intensity and lead variant genotype. Regions with lead variant-dependent accessibility called by caQTLseg are indicated in light blue. Upper panels show full regions of LD, lower panels are close-ups of highlighted regions. Red circles indicate variants that show evidence of association with MM (data from Fig. 1a; variants with P < 10⁻⁵ for association shown). In the lower panels, average local ATAC-seq signal intensity across individuals with different lead variant genotypes is indicated by the yellow (minor/minor), orange (minor/major), and red (major/major) lines.