tooluniverse-phewas
Cross-Biobank PheWAS & Replication
A PheWAS is the inverse of a GWAS: a GWAS fixes a phenotype and scans variants; a PheWAS fixes a variant (or gene) and scans the entire phenome. The scientific payoff of running it across several biobanks is replication and ancestry resolution — an association seen in one population that reappears in another (with the same effect direction) is far more credible, while one that appears only in East-Asian cohorts may reflect ancestry-specific LD, allele frequency, or biology.
This skill orchestrates one variant/gene across four ancestries plus a gene-burden layer. Look up, don't guess — never assert a variant's phenotype associations or effect sizes from memory; the whole point is the live cross-biobank numbers.
The biobank panel
| Tool | Biobank | Ancestry | Build | Evidence type |
|---|---|---|---|---|
UKBTOPMed_phewas_by_variant |
UKB-TOPMed | European (UK) | GRCh38 | per-phenotype assoc (phecodes, ~1,400) |
FinnGen_get_variant_finemapping |
FinnGen | Finnish | GRCh38 | credible-set membership (fine-mapping) |
BioBankJapan_phewas_by_variant |
BioBank Japan | Japanese | GRCh37 | per-phenotype assoc |
TPMI_phewas_by_variant |
TPMI | Taiwanese (Han) | GRCh38 | per-phenotype assoc (ICD-based) |
Genebass_gene_burden_phewas |
Genebass (UKB exomes) | European | GRCh38 | gene-level rare-variant burden |
The four *_phewas_by_variant tools (UKB-TOPMed, BBJ, TPMI) and Genebass_gene_burden_phewas accept an rsID (Genebass also accepts a gene symbol) and resolve coordinates themselves via Ensembl, picking the correct allele for multi-allelic SNPs; the build difference between BBJ-GRCh37 and the others is handled internally — just pass the rsID. You normally do not need to hand-convert coordinates for these.
FinnGen_get_variant_finemapping is the exception: it does NOT accept an rsID. It requires an explicit GRCh38 variant string in chr:pos:ref:alt format (e.g. "10:112998590:C:T"). Resolve the rsID to GRCh38 coordinates first — the simplest way is to read the variant/rsids field returned by the UKB-TOPMed (GRCh38) call, then pass that coordinate string to FinnGen.