SuSiEx

Summary

SuSiEx is a command-line bioinformatics tool designed for cross-population statistical fine-mapping of causal genetic variants. It extends the single-population Sum of Single Effects (SuSiE) model to multi-ancestry cohorts. By integrating GWAS summary statistics and linkage disequilibrium (LD) reference panels from multiple populations, SuSiEx leverages population-specific allele frequencies and LD diversity to identify causal variants with improved power and resolution.

Features and Method

SuSiEx implements a joint statistical framework that: - Models population-specific allele frequencies and LD patterns directly. - Handles multiple causal variants in a genomic region by estimating credible sets. - Calculates posterior inclusion probabilities (PIPs) for each variant. - Can analyze arbitrary numbers of ancestries without requiring individual-level genetic data.

It is implemented as a command-line tool and is competitive in speed and scalability.

Independent Benchmark

A head-to-head benchmark of multi-ancestry fine-mapping methods on real TOPMed MESA pQTL data found SuSiEx produced the smallest, highest-PIP credible sets of the methods tested and the best UK Biobank-replication precision (0.170–0.213), at the cost of the lowest recall (0.036–0.090) — the opposite trade-off from SuShiE and MultiSuSiE. See Multi-Ancestry Proteome-Wide Association Studies for the full comparison.

Citations

• Yuan, K., Longchamps, R. J., Pardiñas, A. F., Yu, M., Chen, T.-T., Lin, S.-C., Chen, Y., Lam, M., Liu, R., Xia, Y., Guo, Z., Shi, W., Shen, C., Psychiatric Genomics Consortium, Daly, M. J., Neale, B. M., Feng, Y.-C. A., Lin, Y.-F., Chen, C.-Y., O'Donovan, M. C., Ge, T., & Huang, H. (2024). Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases. Nature Genetics, 56(9), 1841–1850. Source paper: s41588-024-01870-z.pdf