Table 2.
MAGMA-identified aging mouse bone DEGs with variants associated with human fracture using UK Biobank GWAS results for pairwise comparison age groups of 2m-2y (2y) and 2m-2.5y (2.5y). Some genes are shared in both 2m-2y and 2m-2.5y.
| Age | Human | Mouse | Fracture | Bone Mineral Density | Mouse Gene Expressione | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gene ID | Entrez ID | Gene ID | Entrez ID | MAGMA P-value a | Adjusted P-value b | GWAS P-value c | GWAS SNP rsID d | MAGMA P-value a | Adjusted P-value b | GWAS P-value c | GWAS SNP rsID d | ||
| 2y 2.5y |
WNT16f* | 51384 | Wnt16 | 93735 | 1.7 x 10−25 | 2.4 x 10−22 8.0 x 10−22 |
7.2 x 10−50 | rs2908007 | 1.0 x 10−50 | 1.4 x 10−47 4.7 x 10−47 |
<5 x 10−323 | 56 SNPs | down |
|
| |||||||||||||
| 2.5y | RSPO3 | 84870 | Rspo3 | 72780 | 2.5 x 10−25 | 1.2 x 10−21 | 2.5 x 10−25 | rs7741021 | 1.0 x 10−50 | 4.7 x 10−47 | <5 x 10−323 | 32 SNPs | down |
|
| |||||||||||||
| 2y 2.5y |
FAM3Cf | 10447 | Fam3c | 27999 | 3.3 x 10−24 | 4.6 x 10−21 1.6 x 10−20 |
7.2 x 10−50 | rs2908007 | 1.3 x 10−43 | 1.8 x 10−40 6.1 x 10−40 |
<5 x 10−323 | 43 SNPs | down |
|
| |||||||||||||
| 2y 2.5y |
CPED1f | 79974 | Cped1 | 214642 | 5.9 x 10−16 | 8.2 x 10−13 2.8 x 10−12 |
7.2 x 10−50 | rs2908007 | 1.0 x 10−50 | 1.4 x 10−47 4.7 x 10−47 |
<5 x 10−323 | 111 SNPs | down |
|
| |||||||||||||
| 2y | SOST | 50964 | Sost | 74499 | 1.3 x 10−14 | 1.8 x 10−11 | 1.3 x 10−14 | rs4793022 | 1.0 x 10−50 | 1.4 x 10−47 | 3 x 10−114 | rs2741856 | up |
|
| |||||||||||||
| 2.5y | HROB | 78995 | BC030867 | 217216 | 4.9 x 10−12 | 2.3 x 10−8 | 3.0 x 10−12 | rs408282 | 1.5 x 10−27 | 6.9 x 10−24 | 2.1 x 10−68 | rs228746 | up |
|
| |||||||||||||
| 2.5y | MEOX1 | 4222 | Meox1 | 17285 | 8.0 x 10−12 | 3.8 x 10−8 | 4.6. x 10−14 | rs6503470 | 1.0 x 10−50 | 4.7 x 10−47 | 7.2 x 10−99 | rs9902329 | down |
|
| |||||||||||||
| 2.5y | ATXN7L3 | 56970 | Atxn7l3 | 217218 | 4.5 x 10−11 | 2.1 x 10−7 | 1.9 x 10−11 | rs567375191 | 1.0 x 10−50 | 4.7 x 10−47 | 2.5 x 10−62 | rs2240226 | up |
|
| |||||||||||||
| 2.5y | FGFRL1 | 53834 | Fgfrl1 | 116701 | 1.6 x 10−10 | 7.5 x 10−7 | 7.8 x 10−13 | rs78520297 | 1.8 x 10−21 | 8.5 x 10−18 | 5 x 10−193 | rs4505759 | down |
|
| |||||||||||||
| 2.5y | MPP3 | 4356 | Mpp3 | 13384 | 4.1 x 10−10 | 1.9 x 10−6 | 9.2 x 10−14 | rs540771367 | 1.0 x 10−50 | 4.7 x 10−47 | 5.2 x 10−97 | rs78311416, rs185157719 | down |
|
| |||||||||||||
| 2.5y | LDLRAD4 | 753 | Ldlrad4 | 52662 | 9.1 x 10−8 | 4.3 x 10−4 | 1.5 x 10−10 | rs4430817 | 1.7 x 10−18 | 8.2 x 10−15 | 2 x 10−155 | rs2040189 | down |
|
| |||||||||||||
| 2y 2.5y |
LRP5 | 4041 | Lrp5 | 16973 | 1.0 x 10−7 | 1.4 x 10−4 4.8 x 10−4 |
7.5 x 10−9 | rs11228240 | 1.0 x 10−50 | 1.4 x 10−47 4.7 x 10−47 |
6 x 10−101 | rs11228240 | down |
|
| |||||||||||||
| 2.5y | SFRP4 | 6424 | Sfrp4 | 20379 | 1.1 x 10−6 | 5.3 x 10−3 | 4.9 x 10−9 | rs1047785 | 1.0 x 10−50 | 4.7 x 10−47 | 8 x 10−139 | rs1717740 | down |
|
| |||||||||||||
| 2y 2.5y |
MINDY4 | 84182 | Mindy4 | 330323 | 1.3 x 10−6 | 1.8 x 10−3 6.0 x 10−3 |
1.9 x 10−9 | rs28362709 | 7.5 x 10−25 | 1.1 x 10−21 3.5 x 10−21 |
3.6 x 10−88 | rs28362709 | down |
|
| |||||||||||||
| 2.5y | C11orf49 | 79096 | 1110051M20Rik | 228356 | 1.4 x 10−6 | 6.6 x 10−3 | 2.5 x 10−8 | rs1055447 | 1.0 x 10−50 | 4.7 x 10−47 | 4.6 x 10−79 | rs7118404 | down |
|
| |||||||||||||
| 2.5y | EPDR1 | 54749 | Epdr1 | 105298 | 1.7 x 10−6 | 7.8 x 10−3 | 4.9 x 10−9 | rs1047785 | 1.0 x 10−50 | 4.7 x 10−47 | 1 x 10−168 | rs939667 | down |
|
| |||||||||||||
| 2y 2.5y |
RND1 | 27289 | Rnd1 | 223881 | 4.1 x 10−6 | 5.7 x 10−3 0.019 |
4.2 x 10−8 | rs2926799 | 7.0 x 10−18 | 9.8 x 10−15 3.3 x 10−14 |
3.3 x 10−76 | rs117962372 | up |
|
| |||||||||||||
| 2.5y | MGPg* | 4256 | Mgp | 17313 | 4.3 x 10−6 | 0.020 | 3.9 x 10−8 | rs2430691 | 2.9 x 10−18 | 1.4 x 10−14 | 1.8 x 10−18 | rs2430689 | down |
|
| |||||||||||||
| 2.5y | ARHGDIBg | 397 | Arhgdib | 11857 | 5.6 x 10−6 | 0.026 | 3.9 x 10−8 | rs2430691 | 1.5 x 10−17 | 6.9 x 10−14 | 1.8 x 10−18 | rs2430689 | up |
|
| |||||||||||||
| 2.5y | ERP27g | 121506 | Erp27 | 69187 | 7.1 x 10−6 | 0.033 | 3.9 x 10−8 | rs2430691 | 4.1 x 10−14 | 1.9 x 10−10 | 1.8 x 10−18 | rs2430689 | up |
|
| |||||||||||||
| 2y 2.5y |
GLIS2 | 84662 | Glis2 | 83396 | 9.6 x 10−6 | 0.013 0.045 |
1.6 x 10−7 | rs72766545 | 6.4 x 10−15 | 8.9 x 10−12 3.0 x 10−11 |
6.4 x 10−15 | rs148092711 | down |
|
| |||||||||||||
| 2.5y | NBEAL1 | 65065 | Nbeal1 | 269198 | 1.0 x 10−5 | 0.048 | 1.0 x 10−7 | rs2351774 | 2.1 x 10−15 | 1.0 x 10−47 | 3.3 x 10−21 | rs189962749 | down |
|
| |||||||||||||
| 2y | SMCO3 | 440087 | Smco3 | 654818 | 1.5 x 10−5 | 0.020 | 4.0 x 10−7 | rs1861698 | 3.2 x 10−17 | 4.4 x 10−14 | 2.9 x 10−18 | rs2445411, rs10846065 | down |
|
| |||||||||||||
| 2y | SPON2 | 10417 | Spon2 | 100689 | 1.7 x 10−5 | 0.023 | 1.7 x 10−7 | rs4974591 | 1.0 x 10−50 | 1.4 x 10−47 | 8.3 x 10−80 | rs113727613 | down |
MAGMA gene-based score based on empirical min P-value (Supplemental Table S3).
Multiple testing correction for each mouse DEG using Bonferroni correction method. Significance level: adjusted P-value<0.05 (Supplemental Table S3).
Published UK Biobank GWAS result of most significant SNP P-value across a gene region. This P-value is different than MAGMA empirical P-value.
rsID numbers for the most significant SNP identified in UK Biobank GWAS – in case where multiple significant SNP exist, the number of SNPs are listed.
Gene expression levels from mouse RNA-seq: down = gene expression is downregulated for old animals compared to the young ones (2y vs 2m) up = vice-versa (Supp. Table S1).
These genes have the same most significant GWAS SNPs with WNT16(f*) and MGP(g*) and will not be considered for further mechanistic study.