Fig. 3: Monocyte-specific eQTL pinpointed the role of ADCY3 in obesity.

a Number of identified eGenes significantly associated with at least one locus. b Number of eVariants validated in eQTLGen. c Colocalization analysis between consistent eQTL and 24 published GWAS summary statistics. The top bar plot represents the number of independent loci. The right bar plot represents the frequency of eQTL colocalized with at least one GWAS result. Color in the figure represents the ratio of colocalized loci out of independent loci per GWAS result. d Top 10 consistent eQTL in monocytes ranked by p-value. Y-axis is -log10-transformed p-value, and x-axis represents p-values’ ranks. The top 10 eQTL were colored (purple) and labeled. ADCY3 gene was highlighted. e eQTL effect tagged by rs11687089 per cell-type (p-value = 2.06e-08, beta = − 0.93, CI = [− 1.27, − 0.57], n = 152 samples, LMM adjusting age and sex, for monocytes). The Y-axis is the average expression of ADCY3 per donor. Asterisks indicate significant levels (** < 0.01, *** < 0.001, **** < 0.0001). In box-pots, whiskers expand to minima and maxima, boxes indicate 25th and 75th percentiles, centers represent medians. fADCY3 eQTL in monocytes and body mass index (BMI), obesity class I, and obesity class II. Red and blue dots represent the top and other SNPs of ADCY3 eQTL. The y-axis represents -log10-transformed p-values. The X-axis is genomic coordination (GRCh38). Segments (“ATACseq (Mono.)”) represent open chromatin peaks in isolated monocytes from the cohort superseding our cohort. “Ensembl gene” panel displays genes in the locus. The PP4 is estimated by Bayesian colocalization analysis using Bayes Factors. g–i Summary data-based Mendelian Randomization analyses between ADCY3 eQTL and BMI (g), obesity class I (h) obesity class II (i). The y-axis shows eQTL effect sizes. The X-axis represents GWAS effect sizes. The dashed red line indicates linear fit of Wald-ratio-test. The top cis-eQTL SNP and rest ones are in red and blue, respectively. Estimated p-values of SMR are 8.78e-08 (BMI), 9.14e-05 (obesity class I), and 3.90e-04 (obesity class II) using n = 16 SNPs. Vertical and horizontal error bars are GWAS and eQTL effect sizes (means +/− SD, 95%-CI). j Schematic plot depicting potential roles of ADCY3 eQTL in BMI and obesity (Created in BioRender. Zhan, Q. (2025) https://BioRender.com/c28r787).