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The trans-ancestral genomic architecture of glycemic traits.

ABSTRACT: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10^-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

SUBMITTER: Chen J

PROVIDER: S-EPMC7610958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRainbow trout is a significant fish farming species under temperate climates. Female reproduction traits play an important role in the economy of breeding companies with the sale of fertilized eggs. The objectives of this study are threefold: to estimate the genetic parameters of female reproduction traits, to determine the genetic architecture of these traits by the identification of quantitative trait loci (QTL), and to assess the expected efficiency of a pedigree-based selection (BLUP) or genomic selection for these traits.ResultsA pedigreed population of 1343 trout were genotyped for 57,000 SNP markers and phenotyped for seven traits at 2 years of age: spawning date, female body weight before and after spawning, the spawn weight and the egg number of the spawn, the egg average weight and average diameter. Genetic parameters were estimated in multi-trait linear animal models. Heritability estimates were moderate, varying from 0.27 to 0.44. The female body weight was not genetically correlated to any of the reproduction traits. Spawn weight showed strong and favourable genetic correlation with the number of eggs in the spawn and individual egg size traits, but the egg number was uncorrelated to the egg size traits. The genome-wide association studies showed that all traits were very polygenic since less than 10% of the genetic variance was explained by the cumulative effects of the QTLs: for any trait, only 2 to 4 QTLs were detected that explained in-between 1 and 3% of the genetic variance. Genomic selection based on a reference population of only one thousand individuals related to candidates would improve the efficiency of BLUP selection from 16 to 37% depending on traits.ConclusionsOur genetic parameter estimates made unlikely the hypothesis that selection for growth could induce any indirect improvement for female reproduction traits. It is thus important to consider direct selection for spawn weight for improving egg production traits in rainbow trout breeding programs. Due to the low proportion of genetic variance explained by the few QTLs detected for each reproduction traits, marker assisted selection cannot be effective. However genomic selection would allow significant gains of accuracy compared to pedigree-based selection.

Project description:BackgroundIn this study, we aimed to investigate the molecular basis of lactation as well as to identify the genetic factors that influence milk yield and composition in goats. To achieve these two goals, we have analyzed how the mRNA profile of the mammary gland changes in seven Murciano-Granadina goats at each of three different time points, i.e. 78 d (T1, early lactation), 216 d (T2, late lactation) and 285 d (T3, dry period) after parturition. Moreover, we have performed a genome-wide association study (GWAS) for seven dairy traits recorded in the 1st lactation of 822 Murciano-Granadina goats.ResultsThe expression profiles of the mammary gland in the early (T1) and late (T2) lactation were quite similar (42 differentially expressed genes), while strong transcriptomic differences (more than one thousand differentially expressed genes) were observed between the lactating (T1/T2) and non-lactating (T3) mammary glands. A large number of differentially expressed genes were involved in pathways related with the biosynthesis of amino acids, cholesterol, triglycerides and steroids as well as with glycerophospholipid metabolism, adipocytokine signaling, lipid binding, regulation of ion transmembrane transport, calcium ion binding, metalloendopeptidase activity and complement and coagulation cascades. With regard to the second goal of the study, the performance of the GWAS allowed us to detect 24 quantitative trait loci (QTLs), including three genome-wide significant associations: QTL1 (chromosome 2, 130.72-131.01 Mb) for lactose percentage, QTL6 (chromosome 6, 78.90-93.48 Mb) for protein percentage and QTL17 (chromosome 17, 11.20 Mb) for both protein and dry matter percentages. Interestingly, QTL6 shows positional coincidence with the casein genes, which encode 80% of milk proteins.ConclusionsThe abrogation of lactation involves dramatic changes in the expression of genes participating in a broad array of physiological processes such as protein, lipid and carbohydrate metabolism, calcium homeostasis, cell death and tissue remodeling, as well as immunity. We also conclude that genetic variation at the casein genes has a major impact on the milk protein content of Murciano-Granadina goats.

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The trans-ancestral genomic architecture of glycemic traits.

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