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

Author

Listed:
  • Abram Bunya Kamiza

    (MRC/UVRI and LSHTM
    Malawi Epidemiology and Intervention Research Unit
    University of the Witwatersrand)

  • Sounkou M. Touré

    (MRC/UVRI and LSHTM
    University of Sciences, Techniques and Technologies of Bamako)

  • Feng Zhou

    (University of Cambridge)

  • Opeyemi Soremekun

    (MRC/UVRI and LSHTM)

  • Cheickna Cissé

    (University of Sciences, Techniques and Technologies of Bamako
    University of Sciences, Techniques and Technologies of Bamako)

  • Mamadou Wélé

    (Malawi Epidemiology and Intervention Research Unit
    University of Sciences, Techniques and Technologies of Bamako)

  • 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
    University of Sciences, Techniques and Technologies of Bamako)

  • Eleftheria Zeggini

    (Helmholtz Zentrum München - German Research Center for Environmental Health
    Technical University of Munich and Klinikum Rechts der Isar)

  • Andrew P. Morris

    (University of Manchester)

  • Jennifer L. Asimit

    (University of Cambridge)

  • Tinashe Chikowore

    (University of the Witwatersrand
    Brigham and Women’s Hospital
    Harvard Medical School
    University of the Witwatersrand)

  • Segun Fatumo

    (MRC/UVRI and LSHTM
    Center for Genomics Research and Innovation, NABDA/FMST
    Helmholtz Zentrum München - German Research Center for Environmental Health
    London School of Hygiene and Tropical Medicine)

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.

Suggested Citation

  • 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 & Jef, 2023. "Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41271-0
    DOI: 10.1038/s41467-023-41271-0
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    References listed on IDEAS

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    1. Yiwei Gao & Shuai Xu & Xiaoli Cui & Hao Xu & Yunlong Qiu & Yiqing Wei & Yanli Dong & Boling Zhu & Chao Peng & Shiqi Liu & Xuejun Cai Zhang & Jianyuan Sun & Zhuo Huang & Yan Zhao, 2023. "Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Ananyo Choudhury & Jean-Tristan Brandenburg & Tinashe Chikowore & Dhriti Sengupta & Palwende Romuald Boua & Nigel J. Crowther & Godfred Agongo & Gershim Asiki & F. Xavier Gómez-Olivé & Isaac Kisiangan, 2022. "Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
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