Table 1.
Selection of interesting genes identified in gene-based analyses of the 13 neuroticism phenotypes
| Gene | CHR | Position | Implicated by | Notes |
|---|---|---|---|---|
| SPPL2C | 17 | 43,922,256 | All 13 phenotypes | Only gene GWS associated to all 13 neuroticism phenotypes. Located in known inversion on chromosome 17. Associated to e.g. red blood cell count and Parkinson’s disease47,48. |
| MAPT | 17 | 43,971,702 | 11 of 13 phenotypes | Promotes microtubule assembly and stability. Previously linked to intelligence49 and neurodegenerative disorders (e.g. Parkinson’s and Alzheimer’s disease50,51). |
| DRD2 | 11 | 113,280,317 | 11 of 13 phenotypes | Previously associated to neuroticism sum-score3. D2-receptors are thought to be involved in reward processing. |
| GRM8 | 7 | 126,078,652 | 8 items + sum-score | Not associated to neuroticism before. Has been associated to the response to selective serotonin reuptake inhibitors (SSRI) in depressed individuals52. |
| SORCS3 | 10 | 106,400,859 | Items in the depressed affect cluster and sum-score, but not items in the worry cluster | Signal is driven primarily by 3 items (MIS, MOOD, FED-UP), all part of the depressed affect cluster. SORCS3 has been associated to depression3, and is involved in neuropeptide receptor activity. |
| CADM2 | 3 | 85,008,133 | Items in the worry cluster and sum-score, but not items in the depressed affect cluster | Most strongly associated gene for the worry cluster (P = 2.24 × 10−23), and GWS for all items in this cluster. Linked to BMI in multiple studies53,54 (see genetic correlations between both clusters and BMI in Fig. 3). |
| Region A | 3 | 49.215–50.226 Mb | Depressed affect items | Genes in this region (e.g., C3orf84, RHOA, MST1, APEH) were previously linked to e.g. Crohn’s disease55 and blood protein levels56. A subset of the genes in this region (e.g. IP6K1, CAMKV, SEMA3F) have been associated with educational attainment57. |
| Region B | 3 | 50.264–53.080 Mb | Worry items | Genes in this region (e.g. ALAS1, STAB1, GNL3, ITIH4, TMEM110) have been linked to schizophrenia and autism spectrum disorder in earlier studies58,59. |
All genes that were GWS in gene-based analyses in MAGMA23 on all 13 neuroticism phenotypes are reported in Supplementary Data 33.
CHR: Chromosome on which the gene is located.
Position: Start position of the gene in base pairs (for the regions A and B a start and end position is reported).
Depressed affect and worry refer to two separate sets of 4 items each, i.e., LONE/MIS/MOOD/FED-UP, and NERV-FEEL/WORRY/TENSE/SUF-NERV, respectively.
See Supplementary Table 1 for a description of the item labels.