A genome-wide association study of neuroticism in a population-based sample.
- Authors
- Calboli, Federico C F; Tozzi, Federica; Galwey, Nicholas W; Antoniades, Athos; Mooser, Vincent; Preisig, Martin; Vollenweider, Peter; Waterworth, Dawn; Waeber, Gerard; Johnson, Michael R; Muglia, Pierandrea; Balding, David J
- Year
- 2010
- Journal
- PloS one
- PMID
- 20634892
- DOI
- 10.1371/journal.pone.0011504
- PMCID
- PMC2901337
Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p < 10(-6)) and GPC6 showed suggestive evidence for interaction with age (p approximately = 10(-7)). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.
P-values over genomic location.-log10(p-value) for association with EPQ-N, against genomic location for 1.7 M genotyped and well-imputed SNPs. Top: main SNP effect; middle: sex by SNP interaction; bottom: age by SNP interaction.
LLM interpretation
This figure consists of three Manhattan plots showing $-\log_{10}(p\text{-value})$ for associations between 1.7 million SNPs and neuroticism (EPQ-N) across chromosomes 1–21. The top panel displays the main SNP effect, the middle panel shows the sex-by-SNP interaction, and the bottom panel shows the age-by-SNP interaction. Each plot includes a dashed horizontal line indicating a significance threshold, with several data points exceeding this line across different genomic locations.
EPQ-N distribution by 3-year age groups according to minor allele carrier status at rs9561329.
LLM interpretation
This is a grouped box plot showing neuroticism scores across 3-year age groups (36 to 69) for two genotype groups: GG or GA (light grey) and AA (dark grey). The x-axis represents age and the y-axis represents neuroticism scores. The GG/GA group shows more variability in median scores across age groups, while the AA group maintains a more consistent median score until a decrease is observed in the oldest age groups.
Distribution of EPQ-N score across the subjects.A: Males. B: Females. C: Both sexes.
LLM interpretation
This figure consists of three histograms showing the distribution of EPQ-N (Neuroticism) scores for males (A, blue), females (B, red), and both sexes combined (C, grey). The x-axis represents the Neuroticism score and the y-axis represents frequency. In all three plots, the data is skewed, with higher frequencies observed at lower neuroticism scores and a gradual decline as scores increase.
Kinship plots.Plot (a): histogram of kinship coefficients >0.05; Plot (b): Principal component scores obtained from the kinship matrix. Each point represents an individual with EPQ-N score represented by grey scale as indicated on plot.
LLM interpretation
This figure consists of two panels: (a) a blue histogram showing the frequency of kinship coefficients greater than 0.05, with a primary peak near 0.05 and a secondary peak around 0.25. Panel (b) is a scatter plot of the first two principal component scores (PCA1 vs. PCA2) derived from the kinship matrix. In plot (b), individual data points are colored in a grayscale gradient representing EPQ-N scores, ranging from 0–4.5 (light grey) to 18–23 (black).
| Name | Type |
|---|---|
| age | phenotype |
| Alzheimer's disease | phenotype |
| anxiety | phenotype |
| ARRDC4 local | gene |
| Australian population | cohort |
| Australian twins local | cohort |
| cardiovascular disease | phenotype |
| Caucasians local | phenotype |
| CEU HapMap samples local | cohort |
| CoLaus local | cohort |
| CoLaus study local | cohort |
| dementia | phenotype |
| depression | phenotype |
| DSM-IV | phenotype |
| Emotion | phenotype |
| EPQ-N local | phenotype |
| EPQ-N score local | phenotype |
| EPQ questionnaire local | phenotype |
| EPQ score local | phenotype |
| extraversion | phenotype |
| French sample local | cohort |
| Gaussian-distributed phenotype local | phenotype |
| genetic variants | cohort |
| German sample | cohort |
| GlaxoSmithKline local | drug |
| GPC6 | gene |
| HapMap CEU | cohort |
| high neuroticism-score individuals local | phenotype |
| Lausanne population local | cohort |
| MAMDC1 | gene |
| mood disorders | phenotype |
| Netherlands sample local | cohort |
| Netherlands twin families local | cohort |
| neuroticism | phenotype |
| NKAIN2 | gene |
| NPY | gene |
| PC1 | phenotype |
| Pde4d | gene |
| psychiatric disorders | phenotype |
| psychiatric evaluation local | phenotype |
| psychoticism | phenotype |
| PsyCoLaus local | cohort |
| risk factor | phenotype |
| rs11154221 local | variant |
| rs16126 local | variant |
| rs296410 local | variant |
| rs702543 local | variant |
| rs9561329 local | variant |
| schizophrenia | phenotype |
| sex | phenotype |
| SNP | cohort |
| Social desirability (Lie scale) local | phenotype |
| stress response | phenotype |
| Study cohort (2,149 individuals) local | cohort |
| subthreshold diagnosis local | phenotype |
| UK GP cohort local | cohort |
| US-based sample local | cohort |
| Virginia Adult Twin registry local | cohort |
| Wnt pathway local | drug |
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