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Multiancestry conditional and joint analysis applied to GWAS summary statistics
Open accessAbstract
Conditional and joint (COJO) analysis of genome-wide association study (GWAS) data is a standard post-GWAS analysis for identifying statistically independent associations. Although GWAS meta-analyses are increasingly conducted across multiple ancestry groups, the optimal strategy for multiancestry COJO analysis remains unclear. Here we introduce Manc-COJO, a method for multiancestry COJO analysis. Simulations and real-data analyses show that Manc-COJO improves detection of independent association signals while reducing false positives compared with single-ancestry COJO implemented in genome-wide complex trait analysis (GCTA) and its ad-hoc multiancestry adaptations. We also introduce Manc-COJO:FIX, a follow-up algorithm to identify ancestry-specific independent associations. The C++ implementation of Manc-COJO is over 120-fold faster than GCTA-COJO and supports linkage disequilibrium references derived from either individual-level genotype data or pre-computed matrices, facilitating analyses when data sharing is limited.
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Metadata
- Authors
- Wang, X., Wang, Y., Yang, J., Visscher, P. M., Wray, N. R., & Yengo, L.
- Affiliations
- University of Oxford (GB)
- Westlake University (CN)
- The University of Queensland (AU)
- Corresponding author
- Wang, Xiaotong
- Venue
- Nature Genetics
- Published
- 2026-10-20
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W7172541009
- Cited by
- 1
- References
- 38
- Citations by year
- 2026: 1
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Genetics (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (cc-by)
- Funders
- University of Oxford
- Danmarks Grundforskningsfond
- Snow Medical
- European Research Council
- Australian Research Council (FL180100072, FT220100069)
- National Health and Medical Research Council (1173790)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- false positive reduction, genetic association testing, software package
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