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Meta-Analysis
. 2023 Sep 5;14(1):5403.
doi: 10.1038/s41467-023-41271-0.

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

Abram Bunya Kamiza #  1   2   3 , Sounkou M Touré #  1   4 , Feng Zhou #  5 , Opeyemi Soremekun  1 , Cheickna Cissé  4   6 , Mamadou Wélé  2   6 , Aboubacrine M Touré  6 , Oyekanmi Nashiru  7 , Manuel Corpas  8 , Moffat Nyirenda  9 , Amelia Crampin  2 , Jeffrey Shaffer  10 , Seydou Doumbia  4   11 , Eleftheria Zeggini  12   13 , Andrew P Morris  14 , Jennifer L Asimit  5 , Tinashe Chikowore  3   15   16   17 , Segun Fatumo  18   19   20   21
Affiliations
Meta-Analysis

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

Abram Bunya Kamiza et al. Nat Commun. .

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.

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Conflict of interest statement

At the time of writing, M.C. is associated to Cambridge Precision Medicine Limited, UK. However, the remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Genome-wide association study (GWAS) for lipid traits in individuals of African ancestry.
a, b are Manhattan and QQ plot, respectively for GWAS meta-analysis (N = ~125,000). c, d are Manhattan and QQ plot, respectively for multi-trait analysis of GWAS (MTAG, N = ~125,000). X-axis are the genomic position, the Y-axis represents the log10 of association p-values and the point above the dotted line represented variants significant at p-value < 5 × 10−8. P-values are two-tailed calculated using GWAMA for meta-analysis and MTAG for multi-trait analysis of GWAS, not adjusted for multiple comparisons. Of the 87 (seven novel) loci for the meta-analysis of GWAS and 85 (13 novel) loci for MTAG analyses corresponding to 107 distinct loci (65 shared) were identified. In b, and d is a comparison of the expected distribution of association −log10 p-values under the null distribution. Leftward deviation of the curves from the dotted line of expected values indicated more associated loci than expected.
Fig. 2
Fig. 2. Novel loci associated with lipid traits in individuals of African ancestry from the meta-analysis genome-wide association analysis (N = ~ 125,000).
a Locuszoom plot showing associations around the intergenic regions between NT51B and RDH14 region. b Locuszoom plot showing associations around the intergenic region between MYCN and MYCNOS. c Locuszoom plot showing associations around the CHRM3 region. d Locuszoom plot showing associations around the MGAT2 region.
Fig. 3
Fig. 3. Fine-mapping of lipid traits in individuals of African ancestry.
a Lipid trait correlation measured as Pearson’s correlation in the Uganda genome resource (N = ~125, 000). b flashfm multi-trait fine-mapping generated smaller 99% credible sets (CS99) than JAM single-trait fine-mapping (N = ~125,000).
See this image and copyright information in PMC

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