Fig. 3: Functional characterization for risk variants of 15 BMFFs and pathway enrichment and tissue enrichment for susceptible genes of 15 BMFFs.
From: Genetic architecture of bone marrow fat fraction implies its involvement in osteoporosis risk
a Bar chart represents the proportions for risk variants of 15 BMFFs annotated with each functional category (intron region, gene upstream, and downstream regions, intergenic region, 3′-UTR, 5′-UTR and exon region). b Enrichment analyses for risk variants of 15 BMFFs among regions of histone modification, such as H3K4 monomethylation marks (H3K4me1), H3K4 trimethylation marks (H3K4me3), H3K27 acetylation marks (H3K27ac), H3K36 trimethylation marks (H3K36me3), and H3K9 trimethylation marks (H3K9me3). P value was calculated by two-tailed Fisher’s exact test. c Enrichment analyses for risk variants of thoracic vertebra, lumbar vertebra and proximal femur mean BMFF, respectively, among ten related disease risk loci. The number of candidate variants used was 7838 for Th, 7621 for L, and 7149 for PF. The number of control variants used was 7258 for Th, 7056 for L, and 6.646 for PF. P value was calculated by two-tailed Fisher’s exact test. The error bars represent the 95% confidence interval. d Pathway enrichment analyses of Gene Ontology terms were performed at http://kobas.cbi.pku.edu.cn. Significantly enriched GO terms (unadjusted P < 0.05, two-sided) were identified from the analyses of significant genes for BMFF. Unadjusted P values were calculated by two-tailed Fisher’s exact test. e Tissue expression result for 54 specific tissue types was obtained from GTEx v8 using FUMA. FDR <0.05 was considered statistically significant. Only the result for L5 is shown here. BMFF bone marrow fat fraction, Th thoracic vertebra, L lumbar vertebra, PF proximal femur, LPF left proximal femur, RPF right proximal femur, 3’-UTR 3′-untranslated region, 5′-UTR 5′-untranslated region, H3K4me1 H3K4 monomethylation marks, H3K4me3 H3K4 trimethylation marks, H3K27ac H3K27 acetylation marks, H3K36me3 H3K36 trimethylation marks, H3K9me3 H3K9 trimethylation markers, OR odds ratio, CIs confidence intervals, AN anorexia nervosa, T2DM type 2 diabetes, MM multiple myeloma, MDS myelodysplastic syndrome, AA aplastic anemia.
