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-48696013d6d1d343d8272e8925c204e6 UKB-AFR/trans/AFR/VSTM2L:Q96N03:OID20067:v1:Cardiometabolic/loc1.RData -8c48a4c9b42cc76f219b84ce803430c8 UKB-AFR/trans/AFR/VWF:P04275:OID20256:v1:Cardiometabolic/loc1.RData 258248563d750ca5a3c67ef149655f0f UKB-EUR/CisTrans/A1BG.RData 53ab1b15d09e1669fb3beba2720ef8ad UKB-EUR/CisTrans/AAMDC.RData 4152f7963cc15f95112ba871e8cf9311 UKB-EUR/CisTrans/AARSD1.RData diff --git a/README.md b/README.md index 06523b76d9ed6ee49ba9198726e0bce21069301b..9f34e35ead923f8aa5a86dc948d940f7ba0dcbbc 100644 --- a/README.md +++ b/README.md @@ -12,26 +12,22 @@ tags: # PRISM-models -Protein imputation models trained on UK Biobank Pharma Proteomics Project (UKB-PPP, Olink) data, for -protein-wide association studies with GWAS summary statistics. Each model holds SNP weights, the -per-SNP association table, and the reference LD matrix. +Protein imputation models trained on UK Biobank Pharma Proteomics Project (UKB-PPP, Olink) data from +European-ancestry participants, for protein-wide association studies with GWAS summary statistics. +Each model holds SNP weights, the per-SNP association table, and the reference LD matrix. **Version 2026-10-09** (all trans loci retrained, see below). -| path | ancestry | what one file is | count | -|---|---|---|---| -| `UKB-EUR/CisTrans/.RData` | European | one protein: its cis locus + all its trans loci, merged | 2,877 proteins (2,063 cis + trans, 739 cis only, 75 trans only; 12,197 trans loci) | -| `UKB-AFR/trans/AFR//loc.RData` | African | one trans locus, AFR-only model (6+0) | 117 loci in 104 proteins | -| `UKB-AFR/trans/AFR+EUR//loc.RData` | African | the same locus, AFR + EUR transfer model (6+6) | 117 | +| path | what one file is | count | +|---|---|---| +| `UKB-EUR/CisTrans/.RData` | one protein: its cis locus + all its trans loci, merged | 2,877 proteins (2,063 cis + trans, 739 cis only, 75 trans only; 12,197 trans loci) | -`` is the Olink assay symbol; `CASE` is the UKB-PPP id `Gene:UniProt:OID:v1:Panel`. Seven AFR -loci are `trained = FALSE` placeholders: they share no SNP with any EUR trans locus, or their protein has -no EUR trans model. +`` is the Olink assay symbol. ## What changed in this version -1. **Effect allele fixed; all 12,197 UKB-EUR trans loci retrained.** In our GWAS (PLINK 1.9 `--assoc` on - all 52,253 participants), BETA refers to the minor allele of the full sample. The `A1`/`A2` labels, +1. **Effect allele fixed; all 12,197 trans loci retrained.** In our GWAS (PLINK 1.9 `--assoc` on all + 52,253 participants), BETA refers to the minor allele of the full sample. The `A1`/`A2` labels, however, came from a frequency run restricted to each measurement batch, where PLINK re-picks the minor allele. For variants with MAF ≈ 0.48–0.5 the two disagree, so `A1` named the wrong allele in 280,588 table rows (at least one such variant in 11,433 loci). Labels now come from the genotype @@ -40,8 +36,6 @@ no EUR trans model. were never affected. 2. **PPP1R12A trans locus 2 is now included.** A transient file-system error had silently skipped it. 3. **GRCh38 positions added.** `ss` has a `POS.38` (GRCh38) column next to `BP` (GRCh37). -4. **AFR trans models retrained** against the corrected EUR models, which act as the exterior members - of the 6+6 transfer model. Already in the previous release and kept here: trans loci are at most 3 Mb wide, cut to ± 1.5 Mb around the lead SNP (largest |Z|). Positions come from the repaired GRCh38 rsID map (1,726 rows of the UKB-PPP @@ -49,24 +43,19 @@ release had lifted to another chromosome). ## How the models were built -- **EUR trans loci.** We ran the pQTL GWAS ourselves on individual-level UKB-PPP data: 2,923 proteins, +- **Trans loci.** We ran the pQTL GWAS ourselves on individual-level UKB-PPP data: 2,923 proteins, residualised phenotypes. Trans SNPs have P < 5e-8 / 2,923 and lie outside the gene ± 1 Mb; the MHC is removed. The SNPs are clumped against 1000 Genomes EUR and merged into loci on GRCh38. Each locus is trained as a SUMMIT ensemble (ElNet, LASSO, MCP, MNet, SCAD at six clumping levels r² ∈ {0.01, 0.05, 0.1, 0.2, 0.5, 0.9}, with PUMAS subsampling), combined into one omnibus weight. LD comes from 49,341 UK Biobank EUR individuals. -- **EUR cis.** These are the BLISS UKB cis models for 2,802 proteins. Cis and trans loci are merged +- **Cis loci.** These are the BLISS UKB cis models for 2,802 proteins. Cis and trans loci are merged block-diagonally; a SNP that appears in several loci is kept in the first one only (cis first). -- **AFR trans loci.** The loci come from the UKB-PPP AFR summary statistics, clumped against - 1000 Genomes AFR. Each locus gets six local elastic nets (one per clumping level), trained on about - 1,100 AFR individuals with genotypes and phenotypes. These are stacked by NNLS, either alone (6+0) or - together with the six members of the EUR trans model matched by rsID (6+6). Over the 110 trained loci, - mean held-out R² is 0.077 for the 6+6 models and 0.079 for 6+0, so we ship both. ## File contents -**`UKB-EUR/CisTrans`.** These files use a slim format: only the upper triangle of the LD matrix is -stored. Load them with `load-model-slim.r`. +The files use a slim format: only the upper triangle of the LD matrix is stored. Load them with +`load-model-slim.r`. | object | content | |---|---| @@ -80,25 +69,11 @@ the locus's PUMAS R² (the same for every SNP in a locus), so a protein's total In 14 files, tagged `uppertri-v1-sym`, the full LD matrix differed from its transpose by a few ULP. Their upper triangle is stored as is and mirrored on load. -**`UKB-AFR/trans`.** These files store the full `matrix.LD`; load them with plain `load()`. - -| object | content | -|---|---| -| `weight` | member weights, S × 6 (AFR) or S × 12 (AFR+EUR) | -| `CHECKED` | `alpha` (NNLS stacking weight), `robust`, `used`; omnibus weight = `weight %*% CHECKED$alpha` | -| `ss` | `SNP ID CHR POS.38 BP A1 A2 MAF BETA SE P N CIS LOCI POP Z` | -| `matrix.LD` | LD matrix, AFR reference | -| `R2.PUMAS`, `cv.performance` | held-out R² | -| other | `trained protein CASE POP LOCI CHR cis batch N.train eur.loci CLUMPING eur.overlay eur.loci.overlay` | - ## Loading (R) ```r source("load-model-slim.r") m <- load_model_slim("UKB-EUR/CisTrans/A1BG.RData") # m$weight, m$ss, m$matrix.LD (rebuilt) - -e <- new.env() -load("UKB-AFR/trans/AFR+EUR/VWF:P04275:OID20256:v1:Cardiometabolic/loc1.RData", envir = e) ``` `MANIFEST.md5` lists the md5 of every model file; check it with `md5sum -c MANIFEST.md5`. diff --git 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