Table 1.
Variant-to-Gene Mapping Implicated IBD Putative Effector Genes in HNs
| Implicated genes | PubMed hypothalamus/brain | TPM |
|---|---|---|
| CREM | Inhibition of CRH31 | 8.9 |
| Regulation of PENK expression84 | ||
| Circadian rhythm85 | ||
| Regulation of stress-induced corticosterone release in mice86 | ||
| CNTF | Cortical stress responses32 | 2.5 |
| Neurogenesis in feeding centers of hypothalamus87 | ||
| Secretion of pituitary hormones (PRL, GH)38 | ||
| Neuroprotection and axonal regeneration in retina88 | ||
| FAM111A | — | 4 |
| SLC9B2 (or NHA2) | — | 54.9 |
| SNAI2 (or SLUG) | — | 3.5 |
| LMAN2 | — | 52 |
| PRR7 | Specific removal of excitatory synapses and Wnt inhibition41 | 31.8 |
| PRR7-AS1 | — | 8.4 |
| FOXD1 | Differentiation of anterior hypothalamic neurons36 | 0.1 |
| Pituitary luteinizing hormone expression in mice37 | ||
| PRDM1 (or BLIMP-1) | — | 1.7 |
| UBAC2 | — | 13.8 |
| GPR183 (or EBI2) | Central nervous system autoimmunity and T-cell migration | 2 |
| Neuroinflammation89 | ||
| SKAP2 | — | 16.2 |
| TPD52L2 | Invasiveness of glioblastomas90 | 54.2 |
| ATG16L1 | Neuroinflammation of central nervous system55 | 19.2 |
| Epilepsy91 | ||
| NFKB2 | Deficient anterior pituitary with variable immune-deficiency syndrome39 | 3.2 |
| Neuroprotection of dopaminergic neurons92 | ||
| ACO2 | Neurodegenerative disorders93 | 90.8 |
| PHF5A | — | 27.5 |
| DENND1B | — | 7.1 |
| TCTA | — | 64.7 |
| RHOA | Ghrelin/leptin sensitivity in a subset of hypothalamic neurons35 | 261.5 |
| Social stress responses in dopaminergic neurons33 | ||
| Depression-like behaviors via dendritic remodeling of dopaminergic neurons34 | ||
| STARD3 | — | 26.6 |
| CBX3 | Neural differentiation94 | 43.7 |
| Glioma proliferation95 | ||
| HNRNPA2B1 | — | 82.1 |
| GPR22 | — | 43.7 |
NOTE. Genes implicated leveraging the publicly available IBD summary statistics and ATAC sequencing and promoter-focused Capture C libraries generated in HNs; their reported known functions and their mean relative expression in HNs in TPM were according to RNA sequencing data.
GH, growth hormone; PRL, prolactin; TPM, transcript per million.