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Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits

Author

Listed:
  • Ananyo Choudhury

    (University of the Witwatersrand)

  • Jean-Tristan Brandenburg

    (University of the Witwatersrand)

  • Tinashe Chikowore

    (University of the Witwatersrand
    University of the Witwatersrand)

  • Dhriti Sengupta

    (University of the Witwatersrand)

  • Palwende Romuald Boua

    (University of the Witwatersrand
    Institut de Recherche en Sciences de la Santè)

  • Nigel J. Crowther

    (University of the Witwatersrand)

  • Godfred Agongo

    (Ghana Health Service
    C.K. Tedam University of Technology and Applied Sciences)

  • Gershim Asiki

    (African Population and Health Research Center)

  • F. Xavier Gómez-Olivé

    (University of the Witwatersrand)

  • Isaac Kisiangani

    (African Population and Health Research Center)

  • Eric Maimela

    (University of Limpopo)

  • Matshane Masemola-Maphutha

    (University of Limpopo)

  • Lisa K. Micklesfield

    (University of the Witwatersrand)

  • Engelbert A. Nonterah

    (Ghana Health Service)

  • Shane A. Norris

    (University of the Witwatersrand)

  • Hermann Sorgho

    (Institut de Recherche en Sciences de la Santè)

  • Halidou Tinto

    (Institut de Recherche en Sciences de la Santè)

  • Stephen Tollman

    (University of the Witwatersrand)

  • Sarah E. Graham

    (University of Michigan)

  • Cristen J. Willer

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Scott Hazelhurst

    (University of the Witwatersrand
    University of the Witwatersrand)

  • Michèle Ramsay

    (University of the Witwatersrand
    University of the Witwatersrand)

Abstract

Genetic associations for lipid traits have identified hundreds of variants with clear differences across European, Asian and African studies. Based on a sub-Saharan-African GWAS for lipid traits in the population cross-sectional AWI-Gen cohort (N = 10,603) we report a novel LDL-C association in the GATB region (P-value=1.56 × 10−8). Meta-analysis with four other African cohorts (N = 23,718) provides supporting evidence for the LDL-C association with the GATB/FHIP1A region and identifies a novel triglyceride association signal close to the FHIT gene (P-value =2.66 × 10−8). Our data enable fine-mapping of several well-known lipid-trait loci including LDLR, PMFBP1 and LPA. The transferability of signals detected in two large global studies (GLGC and PAGE) consistently improves with an increase in the size of the African replication cohort. Polygenic risk score analysis shows increased predictive accuracy for LDL-C levels with the narrowing of genetic distance between the discovery dataset and our cohort. Novel discovery is enhanced with the inclusion of African data.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30098-w
    DOI: 10.1038/s41467-022-30098-w
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    as
    1. Karoline Kuchenbaecker & Nikita Telkar & Theresa Reiker & Robin G. Walters & Kuang Lin & Anders Eriksson & Deepti Gurdasani & Arthur Gilly & Lorraine Southam & Emmanouil Tsafantakis & Maria Karalefthe, 2019. "The transferability of lipid loci across African, Asian and European cohorts," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    3. Fiona A. Hagenbeek & René Pool & Jenny Dongen & Harmen H. M. Draisma & Jouke Hottenga & Gonneke Willemsen & Abdel Abdellaoui & Iryna O. Fedko & Anouk Braber & Pieter Jelle Visser & Eco J. C. N. Geus &, 2020. "Heritability estimates for 361 blood metabolites across 40 genome-wide association studies," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    4. Nick Patterson & Alkes L Price & David Reich, 2006. "Population Structure and Eigenanalysis," PLOS Genetics, Public Library of Science, vol. 2(12), pages 1-20, December.
    5. Genevieve L. Wojcik & Mariaelisa Graff & Katherine K. Nishimura & Ran Tao & Jeffrey Haessler & Christopher R. Gignoux & Heather M. Highland & Yesha M. Patel & Elena P. Sorokin & Christy L. Avery & Gil, 2019. "Genetic analyses of diverse populations improves discovery for complex traits," Nature, Nature, vol. 570(7762), pages 514-518, June.
    6. Fiona A. Hagenbeek & René Pool & Jenny Dongen & H. M. Draisma & Jouke Hottenga & Gonneke Willemsen & Abdel Abdellaoui & Iryna O. Fedko & Anouk Braber & Pieter Jelle Visser & Eco J. C. N. Geus & Ko Wil, 2020. "Author Correction: Heritability estimates for 361 blood metabolites across 40 genome-wide association studies," Nature Communications, Nature, vol. 11(1), pages 1-1, December.
    7. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    8. Alice B. Popejoy & Stephanie M. Fullerton, 2016. "Genomics is failing on diversity," Nature, Nature, vol. 538(7624), pages 161-164, October.
    9. Sarah E. Graham & Shoa L. Clarke & Kuan-Han H. Wu & Stavroula Kanoni & Greg J. M. Zajac & Shweta Ramdas & Ida Surakka & Ioanna Ntalla & Sailaja Vedantam & Thomas W. Winkler & Adam E. Locke & Eirini Ma, 2021. "The power of genetic diversity in genome-wide association studies of lipids," Nature, Nature, vol. 600(7890), pages 675-679, December.
    10. L. Duncan & H. Shen & B. Gelaye & J. Meijsen & K. Ressler & M. Feldman & R. Peterson & B. Domingue, 2019. "Analysis of polygenic risk score usage and performance in diverse human populations," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
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    1. 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.
    2. Surina Singh & Ananyo Choudhury & Scott Hazelhurst & Nigel J. Crowther & Palwendé R. Boua & Hermann Sorgho & Godfred Agongo & Engelbert A. Nonterah & Lisa K. Micklesfield & Shane A. Norris & Isaac Kis, 2023. "Genome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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