SNP Heritability for Phenotype 2000

Estimated SNP heritability: 0.0987 (se=0.00701, p=2.59e-45)

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 (0.477). 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: 0.0627 (se=0.00446).

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: 1.0425 (se=0.0135, p=0.000807)
• Mean \(\chi^2\): 1.4573
• Ratio: 0.0929 (se=0.0295)
• \(\lambda_{GC}\): 1.3617

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

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.