Two MS-associated genes, CYP24A1 and CLECL1, showed cell type-specific cis-eQTLs (Fig. 5c,d). Another gene that was previously suggested to be neuron-specific31, SLC12A5, did not show a significant ieQTL in our data. In our analysis, we found that higher CYP24A1 expression is associated with increased risk for MS (Wald ratio = 0.13, P = 7.8 × 10−11) and that the eQTL and GWAS signals are co-localized (PP4 = 1.00). Furthermore, ieQTL analyses showed increasing expression of CYP24A1 with increasing excitatory neuron proportions for the risk allele rs2248137-C (interaction β = 1.92, interaction P = 1.98 × 10−11; Fig. 5c), similar to other neurons (Supplementary Table 12). CYP24A1 encodes for a protein that catalyzes the inactivation of 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D32. Epidemiological studies have proposed vitamin D deficiency as a risk factor for MS33,34, which has recently been validated through MR35–37. Our findings are consistent with a previous report that indicates a shared signal for MS and CYP24A1 cis-eQTL in the frontal cortex38.
