Table of Contents

• Updates
• imputed-v3 Phenotypes
• imputed-v3 Sample QC
• imputed-v3 Variant QC
• imputed-v3 Association model

Updates

With the re-release of UK Biobank genotype imputation (which we term imputed-v3), we have generated an updated set of GWAS summary statistics for the genetics community.

• Increased the number of phenotypes with application UKB31063 and addtl. custom curated phenotypes (see imputed-v3 Phenotypes)
• More liberal inclusion of samples (see imputed-v3 Sample QC)
• Inclusion of more SNPs (see imputed-v3 Variant QC)
• Updates to our association model (imputed-v3 Association model) Our largest change is that for all phenotypes, we have run a female-only and male-only GWAS along with the full set.

Information and scripts from the previous round of GWAS are available in the imputed-v2-gwas subdirectory

imputed-v3 Phenotypes

• Auto-curated phenotypes using PHESANT:

  • Source repository: https://github.com/MRCIEU/PHESANT
  • Customized PHESANT repository: https://github.com/astheeggeggs/PHESANT

• ICD10 codes (all non-coded individuals treated as controls)

• Curated phenotypes in collaboration with the FinnGen consortium

• Phenotypes in both sexes

  • PHESANT: 2891 total (274 continuous / 271 ordinal / 2346 binary)
  • ICD10: 633 binary
  • FinnGen curated: 559

• Phenotypes in females

  • PHESANT: 2393 total (259 continuous / 257 ordinal / 1877 binary)
  • ICD10: 482 binary
  • FinnGen curated: 412

• Phenotypes in males

  • PHESANT: 2305 total (262 continuous / 259 ordinal / 1784 binary)
  • ICD10: 439 binary
  • FinnGen curated: 400

• Unique PHESANT phenotypes: 3011, of which 274 are continuous

• 4203 total unique phenotypes: 3011 PHESANT + 559 finngen + 633 ICD10

• Summary files:

  • phenotypes.both_sexes.tsv.gz
  • phenotypes.female.tsv.gz
  • phenotypes.male.tsv.gz
  • phenotype - phenotype ID
  • description - short description of phenotype
  • source - PHESANT auto-curation, ICD10, or FinnGen
  • n_controls - number of QC positive samples responding negatively to phenotype designation (NA if quantitative)
  • n_cases - number of QC positive samples responding affirmatively to phenotype designation (NA if quantitative)
  • n_missing - number of missing QC positive samples
  • n_non_missing - number of non-missing QC positive samples

imputed-v3 Sample QC

• imputed-v3 parameters
  • Used.in.pca.calculation filter (unrelated samples)
  • sex chromosome aneuploidy filter
  • Use provided PCs for European sample selection to determine British ancestry
    • Use 7 standard deviations away from the 1st 6 PCs
    • Further Filter to self-reported 'white-British' / 'Irish' / 'White'
  • QCed sample count: 361194 samples
• imputed-v2 parameters
  • Used.in.pca.calculation filter (unrelated samples)
  • sex chromosome aneuploidy filter
  • White.british.ancestry filter
  • QCed sample count: 337199 samples

imputed-v3 Variant QC

• imputed-v3 parameters
  • Autosomes and X chromosome (but not pseudo-autosomal region or XY)
  • SNPs from HRC, UK10K, and 1KG imputation (~90 million)
  • INFO score > 0.8
  • MAF > 0.0001
    • Exception: VEP annotated Missense and PTV MAF > 1e-6
  • HWE p-value > 1e-10
  • QCed SNP count: 13.7 million
• imputed-v2 parameters
  • Autosomes only
  • SNPs from HRC imputation (~40 million)
  • INFO score > 0.8
  • MAF > 0.0001
  • QCed SNP count: 10.9 million

imputed-v3 Association model

• imputed-v3 model
  • Linear regression model in Hail (linreg)
  • Three GWAS per phenotype
    • Both sexes
    • Female only
    • Male only
  • Covariates: 1st 20 PCs + sex + age + age^2 + sexage + sexage2
  • Sex-specific covariates: 1st 20 PCs + age + age^2
  • Extra column for variant confidence in case/control phenotypes
    • column name: expected_case_minor_AC
    • Used to filter out false-positive SNPs when case count is low
    • Blog details here
• imputed-v2 model
  • Linear regression model in Hail (linreg)
  • Covariates: 1st 10 PCs + sex