Fig 1.
A) Genome-Wide Association Study (GWAS) summary statistics of genetic association with Bone Mineral Density (BMD) or fractures for 13,753,401 Single Nucleotide Polymorphisms (SNPs) from a study estimated in 426,824 UK Biobank participants study [10]. B) FUMA [16] is a web-based platform utilizing information from multiple biological resources for functional annotation of GWAS results and prioritizing the most likely causal SNPs using information from 18 biological data repositories, including the Genotype-Tissue Expression (GTEx) data. Characterization of significant hits and Genome-wide analysis were conducted with FUMA. C) Heatmap shows the highly expressed genes in multiple tissues of GTEx data.
Fig 2.
Functional consequences of Single Nucleotide Polymorphisms (SNPs) with two different thresholds.
Two different P-value thresholds (A) P≤5×10−8 and (B) P≤5×10−100 were used to filter the Genome-Wide Association Study (GWAS) Summary Statistics. The P-value was computed using the chi-square statistics.
Table 1.
The summary of Genome-Wide Association Study (GWAS) summary statistics for Single-Nucleotide Polymorphisms (SNPs) and mapped genes.
Two different P− value thresholds were used to filter the GWAS summary statistics.
Fig 3.
Manhattan Plot at Single Nucleotide Polymorphisms (SNPs) level.
(A) P≤5×10−8 and (B) P≤5×10−100 were used to filter the Genome-Wide Association Study (GWAS) Summary Statistics. The plot shows the p-values on a log-10 scale (y-axis) by their chromosomal location (x-axis). Genome-wide significance (Red dashed line in the plot) was defined at (A) p = 0.05/103155 = 4.84×10−7 and (B) p = 0.05/1724 = 2.9×10−5, respectively.
Fig 4.
Manhattan Plot at the gene level.
(A) P≤5×10−8 and (B) P≤5×10−100 were used to filter the Genome-Wide Association Study (GWAS) Summary Statistics. The plot shows the p-values on a log-10 scale (y-axis) by their chromosomal location (x-axis). Genome wide significance (Red dashed line in the plot) was defined at (A) p = 0.05/2955 = 1.69×10−5 and (B) p = 0.05/30 = 1.67×10−3, respectively.
Fig 5.
Gene expression heatmap with the Genotype-Tissue Expression v8 representing 30 general tissue types.
Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA GWAS) GENE2FUNC online tool was used to create a heatmap showing gene expression datasets using log2 transformed expression values from a threshold P≤5×10−100 was used to map the genes. Red cells depict higher expression compared to cells filled in blue and yellow represents expression that is not significantly different from other genes.
Fig 6.
Tissue enrichment analysis using MAGMA [20].
The most enriched tissue is the mammary breast tissue. Significantly enriched DEG sets (Pbon<0.05) are highlighted in red. A threshold P≤5×10−100 was used to map the genes.
Fig 7.
Differentially expressed genes (DEG) in 30 major tissues in the GTEx data.
A threshold P≤5×10−8 was used to map the genes. Significantly expressed DEG sets (Pbon<0.05) are highlighted in red.
Table 2.
Summary of known and novel findings for three identified genes (EPDR1, PKDCC, and SPTBN1).