We’re excited to announce that updated UK Biobank SNP-heritability results are now available for the current Neale Lab GWAS release. Read on below for a quick summary of what has changed since the last release, and see the links at the bottom of this post for accessing the results. If you’re looking for a refresher on what SNP heritability is and why we’re estimating it, you can find our previous blog series on heritability on the Neale Lab UK Biobank landing page.

Background

Almost two years ago, we released estimates of SNP-heritability for 2,419 phenotypes in UK Biobank to accompany to GWAS results from the Neale Lab. Last year, the Neale Lab released a second round of GWAS results, expanding both the sample size and the number of phenotypes, as well as refining QC and the association model. An additional 31 biomarker phenotypes and meta-data fixes were added to that GWAS release this summer. It’s our pleasure to now release a corresponding update of the SNP-heritability results to cover those new GWAS results and refine the LD score regression (LDSR) analysis.

New Phenotypes, Refreshed GWAS

With the inclusion of the Round 2 GWAS results, including the additional biomarker data, the total number of available phenotypes has nearly doubled from 2,419 to 4,236 (4,178 of which are unique). In addition to biomarkers, these added phenotypes include a large number of items related to diet, cognition, mental health, and occupations, which were all part of follow-up surveys conducted by UK Biobank.

The Round 2 GWAS also increased sample size by using a more inclusive definition of European ancestry when selecting which participants to include in the GWAS. This change yielded a GWAS sample size of 361,194, compared to 337,199 in the Round 1 GWAS, increasing power for the SNP-heritability analyses.

The phenotypes previously included in the Round 1 release of GWAS and SNP-heritability results were also updated with new GWAS in the larger sample and with an updated association model. Most notably for the LDSR analysis, the new association includes additional PCA covariates and uses PCs estimated within the GWAS sample. We find that these changes are indeed beneficial to controlling stratification (see details here).

Lastly, in addition to the primary GWAS of each phenotype the Round 2 GWAS results include GWAS split by sex and GWAS of both raw and rank-normalized versions of continuous phenotypes. Although we’re mostly focused on SNP-heritability of the primary GWAS of each phenotype in this release (e.g. the combined sex analysis unless the phenoype is sex-specific), LDSR results are available for all 11,685 GWAS covered by these variations.

Standardization of continuous phenotypes

The Round 2 GWAS of both the raw and rank-normalized versions of 305 continuous phenotypes has allowed us to evaluate the impact of this transformation on SNP-heritability results. (By comparison, Round 1 results used rank-normalization for all continuous phenotypes.) As we detail on the heritability results site, we find that the impact of this transformation on the LDSR results is generally limited, but that on average we observe slightly stronger SNP-heritability results when the phenotype is rank-normalized for the GWAS rather than analyzed on the raw scale of the phenotype recorded by UK Biobank. On that basis, our updated SNP-heritability results browser continues to report the results for rank-normalized (IRNT) version of continuous phenotypes as the primary LDSR result.