Table 7.
Comparison of the most significant over-represented canonical pathways and upstream regulators associated with gene modules correlated with all traits in simplex and multiplex ASD populations.
| Canonical pathways | Simplex | Multiplex |
|---|---|---|
| (All traits combined) | –log (p-value)* | |
| Molecular Mechanisms of Cancer | 11.32 | 16.83 |
| Regulation of eIF4 and p70S6K Signaling | 11.02 | 11.41 |
| Estrogen Receptor Signaling | 6.63 | 13.43 |
| ATM Signaling | 13.32 | 6.67 |
| Senescence Pathway | 10.76 | 8.97 |
| Protein Ubiquitination Pathway | 8.80 | 9.29 |
| EIF2 Signaling | 9.55 | 8.48 |
| p70S6K Signaling | 6.92 | 11.01 |
| B Cell Receptor Signaling | 5.64 | 11.40 |
| Hepatic Fibrosis Signaling Pathway | 0.97 | 15.96 |
| mTOR Signaling | 9.11 | 7.56 |
| Protein Kinase A Signaling | 4.03 | 12.29 |
| Huntington's Disease Signaling | 6.58 | 9.18 |
| Synaptogenesis Signaling Pathway | 5.81 | 9.86 |
| PI3K Signaling in B Lymphocytes | 6.02 | 9.59 |
| Thrombin Signaling | 3.11 | 11.79 |
| Hereditary Breast Cancer Signaling | 6.54 | 8.35 |
| Axonal Guidance Signaling | 2.31 | 12.48 |
| Ephrin Receptor Signaling | 7.40 | 7.35 |
| Hypoxia Signaling in the Cardiovascular System | 9.70 | 4.74 |
| Upstream Regulators | Simplex | Multiplex |
| (All traits combined) | p-value of overlap* | (# target genes) |
| HNF4A | 1.86E-59 (728) | 3.19E-46 (821) |
| TP53 | 7.66E-25 (559) | 3.85E-49 (761) |
| ESR1 | 9.81E-16 (396) | 5.86E-54 (606) |
| MYC | 1.57E-14 (353) | 9.34E-30 (485) |
| beta-estradiol | 7.42E-08 (525) | 2.30E-35 (791) |
*
Negative logarithm of the Fisher Exact p-value which represents the probability that the pathway is not over-represented among the respective dataset of genes, where a value of 1.3 is equivalent to a p-value of 0.05.
Bold font indicates association with ASD.
*
Indicates the probability that the trait-associated genes are not among those known to be regulated by the indicated upstream regulator.