Table 7.
Genome-wide association studies review results
| References | Author (s) | Publication year | Tool used to assess neuroticism | Highly significant results a | Summary of overall results concerning trait of interestb | Sample population | Trait |
|---|---|---|---|---|---|---|---|
| The Heidelberg Five’ personality dimensions: Genome-wide associations, polygenic risk for neuroticism, and psychopathology 20 years after assessment | Heilbronner et al. | 2021 | A combination of questionnaires including EPI, STAI-S and others defining a condition interpreted as ‘Emotional Lability’ (ELAB) | - | rs112852264, rs34464186, rs12746528, rs66583506, rs12750662 (unknown category) intergenic: rs2344174, rs34351096, rs17131127, rs35147867 intron: rs7001432 (CSMD1) | HeiDE study (‘Heidelberger Langzeitstudie zu Risikofaktoren und Diagnose chronischer Erkrankungen’); 5133 Germans | EMOTIONAL DYSREGULATION |
| A genome scan of neuroticism in nicotine dependent smokers | Neale et al. | 2005 | EPQ | - | - | 129 families (843 siblings) from the USA | NEUROTICISM |
| A genome-wide association study of emotion dysregulation: Evidence for interleukin 2 receptor alpha | Powers et al. | 2016 | EDS | Intron: rs6602398 (ILR2A, only in males) | Intron: rs6602398 (ILR2A, only in males) | 2600 African American from the USA | EMOTIONAL DYSREGULATION |
| A genome-wide association study of neuroticism in a population-based sample | Calboli et al. | 2010 | EPQ | - | 6 genes: MGC57346, MSRA, XKR6, C17ORF69, KIAA1267 (integrative analysis of genomic and transcriptomic data of genome-wide association study (GWAS) and expression quantitative trait locus (eQTL) study) | UK Biobank, Psychiatric Genomics Consortium | NEUROTICISM |
| A genome-wide linkage study of individuals with high scores on NEO personality traits | Amin et al. | 2012 | NEO-FFi | - | - | 2657 Dutch | NEUROTICISM |
| A genome-wide scan for Eysenckian personality dimensions in adolescent twin sibships: psychoticism, extraversion, neuroticism, and lie | Gillespie et al. | 2008 | EPI | - | Regions on chromosome 16 and 19 | 1280 Australian adolescent twins and their siblings | NEUROTICISM |
| A whole genome association study of neuroticism using DNA pooling | Shifman et al. | 2008 | EPQ-R | - | - | 2000 English people and 1500 English people for replication sample: all of them oversampled for high neuroticism scores | NEUROTICISM |
| Analysis of functional variants reveals new candidate genes associated with alexithymia | Mezzavilla et al. | 2015 | TAS | Exons: rs144957058 (TMEM88B), rs45575636(ABCB4), rs35942033 (TP53AIP1), rs35287114 (ARHGAP32) | 585 healthy adults from the Friuli Venezia Giulia Genetic Park project | ALEXITHYMIA | |
| Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism | Luciano et al. | 2018 | EPQ-R-S | Intergenic: rs72694263, rs7107356, rs7111031, rs2953805, rs10097870, rs2921036 intronic: rs169235 (CACNA1E), rs1521732 (LINGO2, LOC105376004), rs1422192 (LINC00461), rs7175083 (LINGO1), rs7502590 (BAIAP2), rs11082011 (CELF4), rs6982308 (MSRA), rs7005884 (XKR6) UTR3: rs11090045 (ZC3H7B) UTR3: rs11090045 (ZC3H7B) | 116 loci | UK Biobank | NEUROTICISM |
| Gene-based association analysis identifies 190 genes affecting neuroticism | Belonogova et al. | 2021 | EPQ-RS | 57 noncoding variants; Exons: TRIM39-RPP21, RPP21, C12orf49 | 190 genes | UK Biobank | NEUROTICISM |
| Genetic contributions to two special factors of neuroticism are associated with affluence, higher intelligence, better health, and longer life | Hill et al. | 2020 | EPI | 10 intron SNPs, 7 intergenic SNPs, 1 UTR3 (PAX6), 1 exon (DCAF5), 1 upstream (FBXL17) | 51 loci | UK Biobank | NEUROTICISM |
| Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses | Okbay et al. | 2016 | EPI | Intron: rs10960103 (AKAP8P1,JKAMPP1), rs4938021 (LOC105369501), rs139237746 (SBF2), rs1557341 (CELF4), rs12938775 (PAFAH1B1), rs12961969 noncoding transcript variant: rs35688236 (LOC102724048), rs2150462, rs12903563, rs2572431 (inversion-tagging polymorphism on chromosome 8), rs193236081b (Inversion-tagging polymorphism on chromosome 17) | 11 loci | UK Biobank, Psychiatric Genomics Consortium, Resource for Genetic Epidemiology Research on Aging | NEUROTICISM |
| Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci | Smith et al. | 2016 | Intergenic: rs490647, rs12637928, rs12378446, rs4977844 intron: rs4653663 (VRK2), rs62353264 (TMEM192), rs12682352 (MFHAS1), rs111433752 (LINC02210-CRHR1), rs1187264 (RPL12P40) | 9 loci | UK Biobank, Scottish Family Health Study (6659), Queensland Institute of Medical Research Berghofer Medical Research Institute cohort (8687) | NEUROTICISM | |
| Genome-wide association analysis followed by a replication study implicates a novel candidate gene for neuroticism | van den Oord et al. | 2008 | EPQ-R | - | - | 1227 people from the USA | NEUROTICISM |
| Genome-wide association scan for five major dimensions of personality | Terracciano et al. | 2010 | NEO-PI-R | - | rs3026815, rs6047641, rs1159275, rs7329003 | 6148 people from an isolated community in Sardinia, 3900 in the replication sample | NEUROTICISM |
| Genome-wide association study of the five-factor model of personality in young Korean women | Kim et al. | 2013 | NEO-PI-R | - | GWAS: OR1A2 | 1089 Korean women | NEUROTICISM |
| Genome-wide association study of the sensitivity to environmental stress and adversity neuroticism cluster | Nagel et al. | 2020 | EPQ | - | 47 loci | UK Biobank | NEUROTICISM |
| Genome-wide association uncovers shared genetic effects among personality traits and mood states | Luciano et al. | 2012 | EPQ | - | Genes: LCE3C, SCAMP2, POLR3A, ULK3, LMAN1L | Croatia (800), Scotland (400), England (1500), Netherlands (1300) | NEUROTICISM |
| Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism | Fan et al. | 2017 | EPI | - | UK Biobank, Psychiatric Genomics Consortium | NEUROTICISM | |
| Integrative analysis of genome-wide association study and common meQTLs for exploring the effects of DNA methylation on the development of neuroticism | Zhao and Liu | 2020 | EPI | - | 11 genes identified through integrative analysis | UK Biobank, Psychiatric Genomics Consortium | NEUROTICISM |
| Item-level analyses reveal genetic heterogeneity in neuroticism | Nagel et al. | 2018 | EPQ-R-SF | 117 loci (not reported any information on subdivision between introns, intergenic or exons) | 117 loci associated with overall neuroticism score, 138 item-specific | UK Biobank | NEUROTICISM |
| Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative-trait loci that influence variation in the human personality trait neuroticism | Fullerton et al. | 2003 | EPQ | - | Five regions: 1q, 4q, 7p, 12q and 13q | 34580 sibling pairs in the southwest of England | NEUROTICISM |
| Modeling prior information of common genetic variants improves gene discovery for neuroticism | Lo et al. | 2017 | BFI | Intergenic: rs12102100 intron: rs9822731 (CADM2), rs17022974 (CADM2), rs10812851 (LINGO2, LOC105376004), rs9611505 (EP300) | Combination of relative enrichment score (RES) and conditional false discovery rate (FDR): CADM2, LINGO2 and EP300 | 23 and Me database, UK Biobank, Psychiatric Genomics Consortium | NEUROTICISM |
| Multitrait analysis of genome-wide association summary statistics using MTAG | Turley et al. | 2018 | EPI | Noncoding transcript variant rs2572431(LINC00529), rs1187229 (LOC105372072, LOC105372073) intron: rs62057143 (CRHR1, LINC02210-CRHR1), rs10960103 (AKAP8P1,JKAMPP1), rs60827133, rs4938021 (LOC105369501), rs1557341 (CELF4), rs8084351 (DCC), rs10733389, rs10113343 (PINX1), rs9893575 (LOC105371490), rs716804 (SBF2) | 37 loci | UK Biobank | NEUROTICISM |
| Pathway analysis of genome-wide association datasets of personality traits | Kim et al. | 2015 | NEO-PI-R | L1CAM pathway and associated genes | Pathway analysis: L1CAM pathway and associated genes | 1089 Korean women | NEUROTICISM |
| The influence of X chromosome variants on trait neuroticism | Luciano et al. | 2021 | EPQ-R-SF | intergenic: rs6630665, rs764018176, rs177010 intronic: rs5977754 (HS6ST2) | 204 loci on chromosome X | UK Biobank | NEUROTICISM |
| TMPRSS9 and GRIN2B are associated with neuroticism: a genome-wide association study in a European sample | Aragam et al. | 2013 | NEO-FFI | - | GWAS: TMPRSS9 | NESDA cohort 2008 (2000 Dutch) | NEUROTICISM |
a
P equal or lower than 10−8.
b
If not otherwise specified, P value threshold: 5 × 10−6.