Discovery and fine-mapping of lipid traits loci in 125,000 individuals of African ancestry-Reference-Cited by-同舟云学术

Discovery and fine-mapping of lipid traits loci in 125,000 individuals of African ancestry

Published:2023-04-14 Issue: Volume: Page:
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Author:

Kamiza Abram¹,Touré Sounkou²,Zhou Fend³,Soremekun Opeyemi¹,Cissé Cheickna²,Wele Mamadou⁴,Touré Aboubacrine²,Nashiru Oyekanmi⁵,Corpas Manuel⁶,Nyirenda Moffat¹,Crampin Amelia⁷,Shaffer Jeffrey⁸,Doumbia Seydou⁹,Zeggini Eleftheria¹⁰^ORCID,Morris Andrew¹¹^ORCID,Asimit Jennifer¹²^ORCID,Chikowore Tinashe¹³^ORCID,Fatumo Segun¹⁴^ORCID

Affiliation:

1. MRC/UVRI and LSHTM

2. ACE-B

3. MRC

4. African Center of Excellence in Bioinformatics (ACE-B), University of Science, Technique, and Technologies of Bamako (USTTB

5. H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria

6. University of Westminister

7. Karonga Prevention Study, Chilumba, Malawi

8. Tulane University School of Public Health and Tropical Medicine

9. Malaria Research and Training Center

10. Institute of Translational Genomics, Helmholtz Zentrum München

11. University of Manchester

12. University of Cambridge

13. University of Witwatersrand

14. MRC/UVRI & LSHTM Uganda Research Unit

Abstract

Abstract Most of the genome-wide association studies (GWAS) for lipid traits focus on single lipid traits. There are limited GWASs evaluating the variants associated with two or more lipid traits in African ancestry. To further identify and localize genetic loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of genome-wide association studies (MTAG), and multi-trait fine mapping of up to 125,000 individuals of African ancestry. Our GWAS meta-analysis and MTAG identified four and 14 novel loci associated with lipid traits in individuals of African ancestry, respectively. flashfm multi-trait fine-mapping, which leverages information between the traits, 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 JAM. In conclusion, we have identified additional novel loci associated with lipid traits in individuals of African ancestry and our flashfm fine-mapping significantly reduced the 99% credible set size to identify the causal genetic variants associated with multiple lipid traits in individuals of African ancestry.

Publisher

Research Square Platform LLC

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