Phenotype: Guilty feelings

This phenotype can be found on the UK Biobank Showcase for code 2030. Neale Lab GWAS results are available for 351,907 unrelated individuals of European ancestry. This is a binary phenotype with 100,128 cases and 251,779 controls.


Primary Results

Estimated SNP heritability: 0.0950 (se=0.00655, p=5.93e-48)

Significance level: strongly significant after multiple testing correction

Confidence rating: high

Note: SNP heritability for this binary outcome is reported on the liability scale, assuming that the population prevalence matches the prevalence in the UK Biobank analysis set (0.285). This may be unreliable if the outcome was limited to a subset of individuals, or if the UK Biobank study population is not representative for this phenotype (which is likely in many cases). The estimated observed-scale heritability is: 0.0537 (se=0.0037).


Confounding and model misspecification

In addition to SNP heritability, LD score regression also estimates an intercept term that indexes population stratification, other counfounding, and potential misspecification in the partitioned LD score model for the distribution of genetic effects genome-wide.

  • Intercept: 1.0057 (se=0.0125, p=0.325)
  • Mean \(\chi^2\): 1.359
  • Ratio: 0.0158 (se=0.0349)
  • \(\lambda_{GC}\): 1.2899

Intercept values near 1 indicate little or no confounding. The reported LDSR ratio compares the intercept estimate and the mean \(\chi^2\) statistic to provide a rough index for how much of the polygenic signal in the GWAS may be due to confounding rather than genetic effects (assuming the LD score model is well specified). Note that the intercept, mean \(\chi^2\), and genomic control \(\lambda_{GC}\) are all expected to scale with sample size, making the ratio better suited for comparisons between different GWAS.


Correlations

Genetic correlations and phenotypic correlations comparing this phenotype to other significantly heritable phenotypes from the Neale Lab UK Biobank GWAS can be found at: ukbb-rg.hail.is


Partitioned Heritability

Significance of categorical annotations

Two-sided test of the tau coefficient for the named annotation conditional on the rest of the baseline-LD v1.1 model. The orange line indicates Bonferroni-corrected significance across 38 annotations of interest for this phenotype (\(p <\) 1.3e-3). The green line indicates nominal significance (\(p <\) .05). Bonferroni correction excludes the base annotation, 10 MAF bin annotations, and the 26 buffer annotations (extending 500-bp around the baseline functional annotations) since they are primarily intended as statistical controls rather than for direct inference. Note this does not account for multiple testing across phenotypes.


Significance of continuous annotations

Two-sided test of the tau coefficient for the named annotation conditional on the rest of the baseline-LD v1.1 model. The orange line indicates Bonferroni-corrected significance across 38 annotations of interest for this phenotype (\(p <\) 1.3e-3). The green line indicates nominal significance (\(p <\) .05). Bonferroni correction excludes the base annotation, 10 MAF bin annotations, and the 26 buffer annotations (extending 500-bp around the baseline functional annotations) since they are primarily intended as statistical controls rather than for direct inference. Note this does not account for multiple testing across phenotypes.


Methods

All results are from partitioned heritability analysis of this phenotype using LD score regression (Bulik-Sullivan et al. 2015, github repo) with 75 annotations as described by Gazal et al. 2017 (also on biorxiv). See Methods for more information on the underlying GWAS and LDSR analysis. You can also read more about the confidence criteria and the significance thresholds.

Downloads

See the full manifest of LDSR sumstats files for sumstats for other GWAS of this phenotype, where applicable.

See the Downloads page for more information.

Credits

See the full team behind these results here.