Table 3. Expression profiles for 4 genome-wide significant loci in mice osteoblast gene expression experiments and Likelihood-based Causality Model Selection (LCMS) regulatory network analysis in inbred mice.
Cytogenetic Loci | The closest Genea | Nearby Transcriptsb | Experiment 1c | Experiment 2d | Experiment 3e | |
PTH stimulated primary osteoblasts | Differential expression during osteoblast development | LCMS analysis for significant eQTL and trait QTL pairs | ||||
Expression, Direction | P-value | # Traits | Max # pairs | |||
2q11.2 | TBC1D8 | TBC1D8 | 0 | 8.23E-01 | 0 | 0 |
RPL31 | ++ | n.a. | n.a. | n.a. | ||
18q11.2 | OSBPL1A | OSBPL1A | +++ ↓ | 4.59E-03 | 1 | 2 |
IMPACT | ++ | 3.17E-03 | 1 | 2 | ||
1p13.2 | RAP1A | RAP1A | ++ | 2.12E-02 | 3 | 3 |
ADORA3 | n.a. | n.a. | 0 | 0 | ||
8q24.12 | TNFRSF11B* | TNFRSF11B | +++ ↓ | 7.61E-01 | 0 | 0 |
COLEC10* | COLEC10 | n.a. | 1.54E-03 | 1 | 2 |
a SNP locates within a gene.
*: For most significantly associated SNP located on the intergenic regions, the closest nearby gene was listed.
b Transcripts: Transcripts from (1) the closest gene; or (2) genes with target SNP located less than 500K bps on the 5' upstream flanking region.
c PTH stimulated primary osteoblasts: 0: not expressed; ++: expression level > 100 in all 3 replicates; +++: expressed in all 3 replicates and regulated by PTH.
d ANOVA was used to test the differential expression across 7 time points (Day 4, 5, 6, 8, 16, 25 and 30 post-induction) during osteoblast development. Bold: p-value < 0.0083 ( = 0.05/6 available transcripts).
e LCMS analysis: Likelihood-based Causality Model Selection to predict candidate genes causally linked with bone phenotypes. Six bone related traits were tested. For each trait test, at least 2 significant pleiotropy of eQTL and trait QTL pairs was considered evidence for a causally relation to the candidate gene.
c,d,e Results of experiment 1,2 and 3 were obtained from different mice strains and different laboratories.
n.a. Expression level is not available, since transcript is not presented on expression arrays.