Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry

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 and Segun Fatumo ()
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Abram Bunya Kamiza: MRC/UVRI and LSHTM
Sounkou M. Touré: MRC/UVRI and LSHTM
Feng Zhou: University of Cambridge
Opeyemi Soremekun: MRC/UVRI and LSHTM
Cheickna Cissé: University of Sciences, Techniques and Technologies of Bamako
Mamadou Wélé: Malawi Epidemiology and Intervention Research Unit
Aboubacrine M. Touré: University of Sciences, Techniques and Technologies of Bamako
Oyekanmi Nashiru: Center for Genomics Research and Innovation, NABDA/FMST
Manuel Corpas: University of Westminster
Moffat Nyirenda: Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit
Amelia Crampin: Malawi Epidemiology and Intervention Research Unit
Jeffrey Shaffer: Tulane University
Seydou Doumbia: University of Sciences, Techniques and Technologies of Bamako
Eleftheria Zeggini: Helmholtz Zentrum München - German Research Center for Environmental Health
Andrew P. Morris: University of Manchester
Jennifer L. Asimit: University of Cambridge
Tinashe Chikowore: University of the Witwatersrand
Segun Fatumo: MRC/UVRI and LSHTM

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41271-0

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