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

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.

SUBMITTER: Choudhury A

PROVIDER: S-EPMC9095599 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Choudhury Ananyo A Brandenburg Jean-Tristan JT Chikowore Tinashe T Sengupta Dhriti D Boua Palwende Romuald PR Crowther Nigel J NJ Agongo Godfred G Asiki Gershim G Gómez-Olivé F Xavier FX Kisiangani Isaac I Maimela Eric E Masemola-Maphutha Matshane M Micklesfield Lisa K LK Nonterah Engelbert A EA Norris Shane A SA Sorgho Hermann H Tinto Halidou H Tollman Stephen S Graham Sarah E SE Willer Cristen J CJ Hazelhurst Scott S Ramsay Michèle M

Nature communications 20220511 1

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<sup>-8</sup>). Meta-analysis with four other African cohorts (N = 23,718) provides supporting evidence for the LDL-C association with the GATB/FHIP1A region and identifi ...[more]

PMID: 35546142

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Project description:Tenderness is a major quality attribute for fresh beef steaks in the United States, and meat quality traits in general are suitable candidates for genomic research. The objectives of the present analysis were to (1) perform genome-wide association (GWA) analysis for marbling, Warner-Bratzler shear force (WBSF), tenderness, and connective tissue using whole-genome data in an Angus population, (2) identify enriched pathways in each GWA analysis; (3) construct a protein-protein interaction network using the associated genes and (4) perform a μ-calpain proteolysis assessment for associated structural proteins. An Angus-sired population of 2,285 individuals was assessed. Animals were transported to a commercial packing plant and harvested at an average age of 457 ± 46 days. After 48 h postmortem, marbling was recorded by graders' visual appraisal. Two 2.54-cm steaks were sampled from each muscle for recording of WBSF, and tenderness, and connective tissue by a sensory panel. The relevance of additive effects on marbling, WBSF, tenderness, and connective tissue was evaluated on a genome-wide scale using a two-step mixed model-based approach in single-trait analysis. A tissue-restricted gene enrichment was performed for each GWA where all polymorphisms with an association p-value lower than 1 × 10-3 were included. The genes identified as associated were included in a protein-protein interaction network and a candidate structural protein assessment of proteolysis analyses. A total of 1,867, 3,181, 3,926, and 3,678 polymorphisms were significantly associated with marbling, WBSF, tenderness, and connective tissue, respectively. The associate region on BTA29 (36,432,655-44,313,046 bp) harbors 13 highly significant markers for meat quality traits. Enrichment for the GO term GO:0005634 (Nucleus), which includes transcription factors, was evident. The final protein-protein network included 431 interations between 349 genes. The 42 most important genes based on significance that encode structural proteins were included in a proteolysis analysis, and 81% of these proteins were potential μ-Calpain substrates. Overall, this comprehensive study unraveled genetic variants, genes and mechanisms of action responsible for the variation in meat quality traits. Our findings can provide opportunities for improving meat quality in beef cattle via marker-assisted selection.

Dataset Information

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

Publications

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

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