Table 1.
Summary of the 15 prioritized transcriptomic modifier genes where imputed expression is associated with the age of clinical onset of Huntington disease in the GeM-HD cohort
| Gene | Start position (location) | Top P-value | Top Z-score | Striatal CAG modulea | Colocalized (any tissue) | Colocalized (brain) | Description |
|---|---|---|---|---|---|---|---|
| GPR161 | 1:168053997 (1q24) | 4.8 × 10−5 | 4.06 | No | Yes | Yes | G-protein–coupled receptor involved in neuronal tube formation. |
| PMS2 | 7:6012870 (7p22) | 5.1 × 10−5 | 4.05 | No | Yes | Yes | DNA repair pathway, involved in mismatch repair. |
| EIF2AK1 | 7:6061881 (7p22) | 1.1 × 10−5 | 4.40 | Yes (M1) | Yes | Yes | Eukaryotic translation initiation factor. Potential genetic modifier of multiple sclerosis. |
| SUMF2 | 7:56131695 (7p11) | 3.9 × 10−6 | 4.62 | Yes (M20) | Yes | Yes | Sulfatase-modifying factor gene. |
| CHCHD2 | 7:56169262 (7p11) | 5.1 × 10−6 | --4.56 | No | Yes | No | Neurodegenerative disorder risk gene. Localized to mitochondria and involved in mitochondrial respiration. |
| RRM2B | 8:103216730 (8q22) | 6.3 × 10−7 | --4.98 | Yes (M20) | Yes | No | Ribonucleotide reductase, involved in DNA repair and mitochondrial phenotypes. |
| FXYD2 | 11:117671559 (11q23) | 3.9 × 10−5 | --4.11 | No | Yes | No | Subunit of the sodium/potassium-transporting ATPase. Located in the mitochondria. |
| CHRFAM7A | 15:30653443 (15q13) | 2.2 × 10−7 | 5.18 | NA | No | No | Nicotinic acetylcholine receptor fusion protein. |
| GOLGA8H | 15:30896329 (15q13) | 8.7 × 10−8 | 5.35 | No | No | No | Golgin protein gene. |
| ARHGAP11B | 15:30916697 (15q13) | 8.6 × 10−6 | --4.45 | NA | No | No | Human-specific gene, involved in cortical folding. |
| FAN1 | 15:31196055 (15q13) | 4.2 × 10−11 | 6.60 | No | Yes | Yes | Fanconi anemia–associated gene (DNA repair pathway). |
| MTMR10 | 15:31231144 (15q13) | 5.8 × 10−7 | 5.00 | Yes (M7) | No | No | Myotubularin-related protein. |
| KLF13 | 15:31619058 (15q13) | 4.5 × 10−5 | --4.08 | No | No | No | Transcription factor. |
| HMHA1 | 19:1065922 (19p13) | 9.8 × 10−5 | --3.90 | No | No | No | Minor histocompatibility protein, located adjacent to DNA-directed RNA polymerase, POLR2E, as well as ABCA7. |
| ATP4A | 19:36040945 (19q13) | 3.7 × 10−5 | 4.13 | Yes (M20) | No | No | P-type cation-transporting ATPase. Located downstream of a number of FXYD genes. |
Genes are annotated for chromosomal location, whether the expression and GWAS-based signals colocalize and membership to striatal coexpression modules where expression is influenced by Htt CAG repeat lengths. NA, not applicable. Bold text represents that this criteria has been met.
aCAG-dependent coexpression modules from Langfelder et al.