Overall, the results from the gene-based analyses suggest a role for both ‘global’ genes (i.e., affecting (almost) all items and the composite score) and ‘local’ genes, (i.e., affecting only one or a subset of items). In Table 1, a selection of such global and local genes is highlighted. Combined, SNP-based and gene-based analyses on all 13 phenotypes implicated 1,247 genes, of which 651 were not identified in analysis of the sum-score (Supplementary Figs. 18d).Table 1Selection of interesting genes identified in gene-based analyses of the 13 neuroticism phenotypesGeneCHRPositionImplicated byNotes SPPL2C 1743,922,256All 13 phenotypesOnly 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 1743,971,70211 of 13 phenotypesPromotes microtubule assembly and stability. Previously linked to intelligence49 and neurodegenerative disorders (e.g. Parkinson’s and Alzheimer’s disease50,51). DRD2 11113,280,31711 of 13 phenotypesPreviously associated to neuroticism sum-score3. D2-receptors are thought to be involved in reward processing. GRM8 7126,078,6528 items + sum-scoreNot associated to neuroticism before. Has been associated to the response to selective serotonin reuptake inhibitors (SSRI) in depressed individuals52.
