Figure 5. A miRNA-eQTL for miR-4707–3p colocalizes with multiple brain traits.

(A) A locus dot-plot surrounding hsa-mir-4707 on chromosome 14 showing -Log₁₀(p-value) for various associations. Top track shows associations for expression of miR-4707–3p with the index variant, rs4981455. The second track shows associations surrounding a significant mRNA-eQTL to HAUS4 expression. The third track shows associations at this locus for a GWAS to educational attainment. The fourth track shows variant associations to global cortical surface area (GSA). Variants are colored by pairwise linkage disequilibrium (LD, r²) to rs4981455 in each of the four tracks. Dotted line in the first and second tracks represent a stringent p-value significance threshold of 1.43x10^–6 and 8.17x10^–4 respectively after local and global multiple testing correction at FDR <5%. Dotted lines in bottom two tracks represents the global genome-wide significance threshold of 5x10^–8. (B) Boxplot showing variance stabilizing transformed (VST) expression of miR-4707–3p for samples with the indicated genotype at rs4981455. Samples with the G/G genotype show no expression of miR-4707–3p. (C) Boxplot showing VST expression of HAUS4, the host gene for mir-4707, at rs4981455.

Figure 5—figure supplement 1. MiR-4707–3p Alternate Allele Expression.

(A) The primary sequence for hsa-mir-4707 is located within the 5’ UTR of the HAUS4 gene on chromosome 14. miR-4707–3p contains a variant, rs2273626 (reference allele C, alternate allele A), within the seed sequence in high LD with the index variant, rs4981455 (r² >0.99). (B) Sequencing read counts per million, as quantified by miRge 2.0, across the three genotypes for both the index variant and seed variant. All samples with index variant G/G showed zero reads. (C) Allele specific expression for heterozygous samples at the seed variant, rs2273626. A total of three reads across three independent donors were observed with the A allele. p-value = 3.23 × 10^–14 when using a paired, two-sided t-test.

Figure 5—figure supplement 2. Conditional analysis show miR-4707–3p colocalizes with educational attainment.

(A) A locus dot-plot surrounding hsa-mir-4707 on chromosome 14 showing -Log₁₀(p-value) as in Figure 5A. Top track shows associations for expression of miR-4707–3p with the index variant, rs4981455. Variants are colored by LD to rs4981455 within the diverse ancestry population of this study. The second track shows associations to educational attainment and the index variant, rs1043209. Variants in this locus are colored by LD to rs1043209 within the 1000 Genomes European populations. The bottom track shows associations for miR-4707–3p expression after including rs1043209 genotypes in the regression equation. Dotted lines in the top and bottom tracks represent a stringent p-value significance threshold of 1.43x10^–6. Dotted line in the middle track represents the global genome-wide significance threshold of 5x10^–8. (B) Association p-values from the first and second track in panel A are plotted against each other. Variants are colored by LD to the educational attainment index variant, rs1043209, using the diverse ancestry population of this study. Index variant for miR-4707–3p expression, rs4981455, is also labeled. Pearson correlation coefficient of 0.898 with p-value of 5.1x10^–107 show a significant correlation between variants in both datasets.