Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry
Abstract Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic ef...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41271-0 |
| _version_ | 1797557914360086528 |
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| author | Abram Bunya Kamiza Sounkou M. Touré Feng Zhou Opeyemi Soremekun Cheickna Cissé Mamadou Wélé Aboubacrine M. Touré Oyekanmi Nashiru Manuel Corpas Moffat Nyirenda Amelia Crampin Jeffrey Shaffer Seydou Doumbia Eleftheria Zeggini Andrew P. Morris Jennifer L. Asimit Tinashe Chikowore Segun Fatumo |
| author_facet | Abram Bunya Kamiza Sounkou M. Touré Feng Zhou Opeyemi Soremekun Cheickna Cissé Mamadou Wélé Aboubacrine M. Touré Oyekanmi Nashiru Manuel Corpas Moffat Nyirenda Amelia Crampin Jeffrey Shaffer Seydou Doumbia Eleftheria Zeggini Andrew P. Morris Jennifer L. Asimit Tinashe Chikowore Segun Fatumo |
| author_sort | Abram Bunya Kamiza |
| collection | DOAJ |
| description | Abstract Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of GWAS (MTAG), and multi-trait fine-mapping (flashfm) in 125,000 individuals of African ancestry. Our meta-analysis and MTAG identified four and 14 novel loci associated with lipid traits, respectively. flashfm yielded an 18% mean reduction in the 99% credible set size compared to single-trait fine-mapping with JAM. Moreover, we identified more genetic variants with a posterior probability of causality >0.9 with flashfm than with JAM. In conclusion, we identified additional novel loci associated with lipid traits, and flashfm reduced the 99% credible set size to identify causal genetic variants associated with multiple lipid traits in African ancestry. |
| first_indexed | 2024-03-10T17:22:59Z |
| format | Article |
| id | doaj.art-fda3a3062d654543b37f9904f3bc6787 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:22:59Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-fda3a3062d654543b37f9904f3bc67872023-11-20T10:16:57ZengNature PortfolioNature Communications2041-17232023-09-0114111010.1038/s41467-023-41271-0Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestryAbram Bunya Kamiza0Sounkou M. Touré1Feng Zhou2Opeyemi Soremekun3Cheickna Cissé4Mamadou Wélé5Aboubacrine M. Touré6Oyekanmi Nashiru7Manuel Corpas8Moffat Nyirenda9Amelia Crampin10Jeffrey Shaffer11Seydou Doumbia12Eleftheria Zeggini13Andrew P. Morris14Jennifer L. Asimit15Tinashe Chikowore16Segun Fatumo17The African Computational Genomic (TACG) Research Group, MRC/UVRI and LSHTMThe African Computational Genomic (TACG) Research Group, MRC/UVRI and LSHTMMRC Biostatistics Unit, University of CambridgeThe African Computational Genomic (TACG) Research Group, MRC/UVRI and LSHTMAfrican Center of Excellence in Bioinformatics, University of Sciences, Techniques and Technologies of BamakoMalawi Epidemiology and Intervention Research UnitFaculty of Sciences and Techniques, University of Sciences, Techniques and Technologies of BamakoH3Africa Bioinformatics Network (H3ABioNet) Node, Center for Genomics Research and Innovation, NABDA/FMSTSchool of Life sciences, University of WestminsterMedical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research UnitMalawi Epidemiology and Intervention Research UnitDepartment of Biostatistics and Data Science, School of Public Health and Tropical Medicine, Tulane UniversityAfrican Center of Excellence in Bioinformatics, University of Sciences, Techniques and Technologies of BamakoInstitute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental HealthCentre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, University of ManchesterMRC Biostatistics Unit, University of CambridgeSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the WitwatersrandThe African Computational Genomic (TACG) Research Group, MRC/UVRI and LSHTMAbstract Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of GWAS (MTAG), and multi-trait fine-mapping (flashfm) in 125,000 individuals of African ancestry. Our meta-analysis and MTAG identified four and 14 novel loci associated with lipid traits, respectively. flashfm yielded an 18% mean reduction in the 99% credible set size compared to single-trait fine-mapping with JAM. Moreover, we identified more genetic variants with a posterior probability of causality >0.9 with flashfm than with JAM. In conclusion, we identified additional novel loci associated with lipid traits, and flashfm reduced the 99% credible set size to identify causal genetic variants associated with multiple lipid traits in African ancestry.https://doi.org/10.1038/s41467-023-41271-0 |
| spellingShingle | Abram Bunya Kamiza Sounkou M. Touré Feng Zhou Opeyemi Soremekun Cheickna Cissé Mamadou Wélé Aboubacrine M. Touré Oyekanmi Nashiru Manuel Corpas Moffat Nyirenda Amelia Crampin Jeffrey Shaffer Seydou Doumbia Eleftheria Zeggini Andrew P. Morris Jennifer L. Asimit Tinashe Chikowore Segun Fatumo Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry Nature Communications |
| title | Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry |
| title_full | Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry |
| title_fullStr | Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry |
| title_full_unstemmed | Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry |
| title_short | Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry |
| title_sort | multi trait discovery and fine mapping of lipid loci in 125 000 individuals of african ancestry |
| url | https://doi.org/10.1038/s41467-023-41271-0 |
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