Flowchart of the study.

Ind: individual.

Fine-mapping result summary.

Grey bar plots indicated the number of loci with posterior inclusion probability (PIP)>0.95 in HFS+SUSIE (causal loci). Black bar plots indicated number of SNP with PIP>0.95 in PolyFun or SbayesRC analysis (the larger number was shown). Each grid of heatmap showed the Odds ratio of each sequence class loci being causal loci for each trait. “All_OR” indicated Odds ratio for pooling all traits together. Enh: enhancer. TF: transcription factor binding site.

Biological enrichment analysis based on HFS fine-mapping.

X-axis indicated t statistics of the analyzed term in a multivariate linear regression (Method). Cell: single-cell ATAC peak for 222 cell types from Zhang et al(K. Zhang et al., 2021). Tissue: active chromatin regions of 222 tissues from epimap(Boix et al., 2021). For each trait, we showed the most significant term plus one or two terms with high biological interpretation that also passed significance threshold. Full enrichment result was shown in Table S7 and S8.

HFS linked trait to causal genes.

A: Target genes of causal loci identified by HFS+SUSIE for platelet count. Only genes that showed functional convergence were shown. B: Regional plot for RBBP5. HFS: loci PIP calculated by HFS+SUSIE. SNP: SNP PIP calculated by PolyFun. cCRE: credible cis-regulation elements. C: Regional plot of MHC region for asthma. Thickened curve linked highlighted causal loci to its target genes predicted by cS2G(Gazal et al., 2022).

HFS-based polygenic prediction.

A: Prediction R2 of HFS-based polygenic risk score (PRS) using different threshold of PIP. allSNP: SNP-based PRS calculated by LDAK-BOLT(Q. Zhang et al., 2021). n: number of features included in the corresponding PRS. B: Prediction R2 of per-block HFS score in British European test set by different methods. EN: elastic net. C: Prediction R2 of different tools in non-British European (NBE), South Asian (SAS), East Asian (EAS) and African (AFR) groups in UK Biobank.