Table 1 Selection of interesting genes identified in gene-based analyses of the 13 neuroticism phenotypes

From: Item-level analyses reveal genetic heterogeneity in neuroticism

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.

  1. All genes that were GWS in gene-based analyses in MAGMA23 on all 13 neuroticism phenotypes are reported in Supplementary Data 33.
  2. CHR: Chromosome on which the gene is located.
  3. Position: Start position of the gene in base pairs (for the regions A and B a start and end position is reported).
  4. 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.
  5. See Supplementary Table 1 for a description of the item labels.
Back to article page