Cross-ancestry / cross-biobank phenome-wide association (PheWAS) and replication. Given ONE variant (rsID) or ONE gene, look up every phenotype it associates with across European/UK (UKB-TOPMed), Finnish (FinnGen), Japanese (BioBank Japan), and Taiwanese (TPMI) biobanks, plus exome-wide gene-burden PheWAS (Genebass), then judge whether an association replicates across ancestries or is population-specific. Use whenever the user asks "what else is this variant/gene associated with", "does this association replicate in other ancestries / biobanks", "is this effect East-Asian-specific", "pleiotropy of rsXXX", "phenome scan", or wants to compare effect sizes/allele frequencies of a variant across populations. NOT for the forward direction (trait → which SNPs: use the gwas-* skills), NOT for fine-mapping a locus (use tooluniverse-gwas-finemapping), and NOT for single-SNP mechanism tracing in one population (use tooluniverse-gwas-snp-interpretation).
Cross-ancestry / cross-biobank phenome-wide association (PheWAS) and replication. Given ONE variant (rsID) or ONE gene, look up every phenotype it associates with across European/UK (UKB-TOPMed), Finnish (FinnGen), Japanese (BioBank Japan), and Taiwanese (TPMI) biobanks, plus exome-wide gene-burden PheWAS (Genebass), then judge whether an association replicates across ancestries or is population-specific. Use whenever the user asks "what else is this variant/gene associated with", "does this association replicate in other ancestries / biobanks", "is this effect East-Asian-specific", "pleiotropy of rsXXX", "phenome scan", or wants to compare effect sizes/allele frequencies of a variant across populations. NOT for the forward direction (trait → which SNPs: use the gwas-* skills), NOT for fine-mapping a locus (use tooluniverse-gwas-finemapping), and NOT for single-SNP mechanism tracing in one population (use tooluniverse-gwas-snp-interpretation).
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.
Workflow
Step 1 — Decide variant-level vs gene-level
Have an rsID / specific variant → variant-level panel (the four *_phewas_by_variant + FinnGen). This is the common case. Pass the rsID directly to the four *_phewas_by_variant tools; for FinnGen_get_variant_finemapping you must supply an explicit GRCh38 chr:pos:ref:alt string (resolve the rsID first — see "The biobank panel" note above).
Have a gene and care about rare coding burden (e.g. "what does loss-of-function of PCSK9 do?") → Genebass_gene_burden_phewas with burden_set: "pLoF". Add the variant panel too if a specific common variant is also of interest.
Step 2 — Query the panel in parallel
Call the relevant tools for the same rsID. Always pass max_pval: 5e-8 (genome-wide significance) for the variant tools when you want only robust hits, or omit it to see suggestive associations too. Example anchor call:
UKBTOPMed_phewas_by_variant(rsid="rs7903146", max_pval=5e-8, limit=25)
BioBankJapan_phewas_by_variant(rsid="rs7903146", max_pval=5e-8, limit=25)
TPMI_phewas_by_variant(rsid="rs7903146", max_pval=5e-8, limit=25)
FinnGen_get_variant_finemapping(variant="10:112998590:C:T") # FinnGen needs a variant string (GRCh38) or use an rsID-resolved coord
Phenotype coding differs per biobank (UKB/TPMI use phecodes, BBJ uses curated endpoints, FinnGen uses its own endpoint codes, Genebass uses UKB field codes). Match on the human-readable name / disease concept, not the code. Group associations into shared concepts (e.g. "Type 2 diabetes" across all of them) before comparing.
Step 4 — Judge replication (see interpretation table)
For each shared phenotype concept, compare significance, effect-size direction (sign of beta), and allele frequency across biobanks.
Step 5 — Report
Use the report template below. Lead with what replicates, then ancestry-specific signals, then caveats.
Interpretation
Pattern across biobanks
Meaning
Significant + same beta sign in ≥2 ancestries
Replicated, robust association — highest confidence
Significant in European but not East-Asian
May be European-specific, OR underpowered / lower allele frequency in East-Asian cohort — check af and num_cases before concluding biology
Significant only in BBJ/TPMI
Candidate East-Asian-specific effect (ancestry-specific LD or biology) — flag for follow-up
Opposite beta signs between biobanks
Caution: possible strand/allele-coding mismatch, or genuine flip — verify the ref/alt allele each biobank reported before interpreting
Variant-level null but Genebass burden significant
Phenotype driven by rare coding variation in the gene, not the common variant
FinnGen credible-set hit but weak elsewhere
Variant is a fine-mapped candidate in Finns; credible-set membership ≠ p-value, so treat as corroborating, not quantitative
Allele-frequency caveat is central. A "missing" association in one population is only interesting after you confirm the variant is actually common enough there to be powered. Each *_phewas_by_variant result carries af, num_cases, num_controls — use them. A variant at AF 0.30 in Europeans but 0.02 in Japanese will look "European-specific" purely from power, not biology.
Running the panel on rs7903146 returns Type 2 diabetes as the top hit with the T (risk) allele increasing risk (β>0) in every ancestry — UKB-TOPMed (p1e-134), BioBank Japan (native Japanese T2D endpoint p2e-47; its external Suzuki-2024 meta entries underflow to pval: 0.0), and TPMI (p6e-11) — concordant positive effect across European, Japanese, and Taiwanese ancestries → textbook replicated association. (Exact p-values drift as biobanks update; treat these as illustrative.) The weaker TPMI p-value tracks the lower T-allele frequency in East Asians (AF0.29 in Europeans vs ~0.02–0.05 in East Asians) and smaller case count, not a weaker biological effect — exactly the power caveat above. A nice secondary signal: in BBJ the T2D-risk allele associates with lower BMI/body weight, the known TCF7L2 feature that it acts through insulin secretion rather than adiposity. This is the canonical robustly-replicated common-variant association and a good sanity check that the panel is working.
Reading pval: 0.0: a returned p-value of exactly 0.0 is floating-point underflow on an astronomically significant association (the true value is below ~1e-308), not "no association." Treat it as the strongest possible hit, not a null.
BioBank Japan catalogue note: the BBJ PheWeb surfaces both native BBJ endpoints and external multi-ancestry GWAS meta-analyses (e.g. Suzuki 2024, with separate EUR/EAS/AFA/SAS/HIS rows). This is a bonus — you get per-ancestry betas from one call — but do not double-count the meta-analysis rows as independent "Japanese" evidence; the native BBJ endpoint is the Japanese-specific one.
Limitations
Variant-level only reports what each biobank pre-computed. PheWeb instances return summary associations, not raw genotypes; you cannot run a custom phenotype not in their catalogue.
TPMI / BBJ phenotype catalogues are ICD/endpoint-based and less granular than UKB phecodes; absence of a phenotype may mean "not catalogued", not "no association".
Genebass is European (UKB exomes) only — it adds a rare-variant burden layer but not an ancestry dimension.
No automatic meta-analysis. This skill compares biobanks qualitatively (replication, direction, power). For a formal cross-ancestry meta-analysis or fine-mapping, hand off to dedicated tooling (tooluniverse-mendelian-randomization, tooluniverse-gwas-finemapping).
FinnGen evidence is credible-set membership, a different currency than the PheWeb p-values; do not put its "hits" on the same numeric axis.
