Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle

Metabolites, substrates or products of metabolic processes, are involved in many biological functions, such as energy metabolism, signaling, stimulatory and inhibitory effects on enzymes and immunological defense. Metabolomic phenotypes are influenced by combination of genetic and environmental effe...

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Main Authors: Jiyuan Li, Everestus C. Akanno, Tiago S. Valente, Mohammed Abo-Ismail, Brian K. Karisa, Zhiquan Wang, Graham S. Plastow
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-09-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2020.538600/full
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author Jiyuan Li
Everestus C. Akanno
Tiago S. Valente
Tiago S. Valente
Mohammed Abo-Ismail
Mohammed Abo-Ismail
Brian K. Karisa
Zhiquan Wang
Graham S. Plastow
author_facet Jiyuan Li
Everestus C. Akanno
Tiago S. Valente
Tiago S. Valente
Mohammed Abo-Ismail
Mohammed Abo-Ismail
Brian K. Karisa
Zhiquan Wang
Graham S. Plastow
author_sort Jiyuan Li
collection DOAJ
description Metabolites, substrates or products of metabolic processes, are involved in many biological functions, such as energy metabolism, signaling, stimulatory and inhibitory effects on enzymes and immunological defense. Metabolomic phenotypes are influenced by combination of genetic and environmental effects allowing for metabolome-genome-wide association studies (mGWAS) as a powerful tool to investigate the relationship between these phenotypes and genetic variants. The objectives of this study were to estimate genomic heritability and perform mGWAS and in silico functional enrichment analyses for a set of plasma metabolites in Canadian crossbred beef cattle. Thirty-three plasma metabolites and 45,266 single nucleotide polymorphisms (SNPs) were available for 475 animals. Genomic heritability for all metabolites was estimated using genomic best linear unbiased prediction (GBLUP) including genomic breed composition as covariates in the model. A single-step GBLUP implemented in BLUPF90 programs was used to determine SNP P values and the proportion of genetic variance explained by SNP windows containing 10 consecutive SNPs. The top 10 SNP windows that explained the largest genetic variation for each metabolite were identified and mapped to detect corresponding candidate genes. Functional enrichment analyses were performed on metabolites and their candidate genes using the Ingenuity Pathway Analysis software. Eleven metabolites showed low to moderate heritability that ranged from 0.09 ± 0.15 to 0.36 ± 0.15, while heritability estimates for 22 metabolites were zero or negligible. This result indicates that while variations in 11 metabolites were due to genetic variants, the majority are largely influenced by environment. Three significant SNP associations were detected for betaine (rs109862186), L-alanine (rs81117935), and L-lactic acid (rs42009425) based on Bonferroni correction for multiple testing (family wise error rate <0.05). The SNP rs81117935 was found to be located within the Catenin Alpha 2 gene (CTNNA2) showing a possible association with the regulation of L-alanine concentration. Other candidate genes were identified based on additive genetic variance explained by SNP windows of 10 consecutive SNPs. The observed heritability estimates and the candidate genes and networks identified in this study will serve as baseline information for research into the utilization of plasma metabolites for genetic improvement of crossbred beef cattle.
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spelling doaj.art-98d810e5ccb24597bd88228e11a30b6f2022-12-22T00:58:57ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-09-011110.3389/fgene.2020.538600538600Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef CattleJiyuan Li0Everestus C. Akanno1Tiago S. Valente2Tiago S. Valente3Mohammed Abo-Ismail4Mohammed Abo-Ismail5Brian K. Karisa6Zhiquan Wang7Graham S. Plastow8Livestock Gentec, Department of Agriculture, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, CanadaLivestock Gentec, Department of Agriculture, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, CanadaLivestock Gentec, Department of Agriculture, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, CanadaDepartment of Animal Science, Ethology and Animal Ecology Research Group, São Paulo State University, Jaboticabal, BrazilLivestock Gentec, Department of Agriculture, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, CanadaDepartment of Animal Science, College of Agriculture, Food and Environmental Sciences, California Polytechnic State University, San Luis Obispo, CA, United StatesMinistry of Agriculture and Forestry, Edmonton, AB, CanadaLivestock Gentec, Department of Agriculture, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, CanadaLivestock Gentec, Department of Agriculture, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, AB, CanadaMetabolites, substrates or products of metabolic processes, are involved in many biological functions, such as energy metabolism, signaling, stimulatory and inhibitory effects on enzymes and immunological defense. Metabolomic phenotypes are influenced by combination of genetic and environmental effects allowing for metabolome-genome-wide association studies (mGWAS) as a powerful tool to investigate the relationship between these phenotypes and genetic variants. The objectives of this study were to estimate genomic heritability and perform mGWAS and in silico functional enrichment analyses for a set of plasma metabolites in Canadian crossbred beef cattle. Thirty-three plasma metabolites and 45,266 single nucleotide polymorphisms (SNPs) were available for 475 animals. Genomic heritability for all metabolites was estimated using genomic best linear unbiased prediction (GBLUP) including genomic breed composition as covariates in the model. A single-step GBLUP implemented in BLUPF90 programs was used to determine SNP P values and the proportion of genetic variance explained by SNP windows containing 10 consecutive SNPs. The top 10 SNP windows that explained the largest genetic variation for each metabolite were identified and mapped to detect corresponding candidate genes. Functional enrichment analyses were performed on metabolites and their candidate genes using the Ingenuity Pathway Analysis software. Eleven metabolites showed low to moderate heritability that ranged from 0.09 ± 0.15 to 0.36 ± 0.15, while heritability estimates for 22 metabolites were zero or negligible. This result indicates that while variations in 11 metabolites were due to genetic variants, the majority are largely influenced by environment. Three significant SNP associations were detected for betaine (rs109862186), L-alanine (rs81117935), and L-lactic acid (rs42009425) based on Bonferroni correction for multiple testing (family wise error rate <0.05). The SNP rs81117935 was found to be located within the Catenin Alpha 2 gene (CTNNA2) showing a possible association with the regulation of L-alanine concentration. Other candidate genes were identified based on additive genetic variance explained by SNP windows of 10 consecutive SNPs. The observed heritability estimates and the candidate genes and networks identified in this study will serve as baseline information for research into the utilization of plasma metabolites for genetic improvement of crossbred beef cattle.https://www.frontiersin.org/article/10.3389/fgene.2020.538600/fullcandidate genescrossbred beef cattlefunctional enrichment analysesmetabolomicssingle-step GBLUP
spellingShingle Jiyuan Li
Everestus C. Akanno
Tiago S. Valente
Tiago S. Valente
Mohammed Abo-Ismail
Mohammed Abo-Ismail
Brian K. Karisa
Zhiquan Wang
Graham S. Plastow
Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle
Frontiers in Genetics
candidate genes
crossbred beef cattle
functional enrichment analyses
metabolomics
single-step GBLUP
title Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle
title_full Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle
title_fullStr Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle
title_full_unstemmed Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle
title_short Genomic Heritability and Genome-Wide Association Studies of Plasma Metabolites in Crossbred Beef Cattle
title_sort genomic heritability and genome wide association studies of plasma metabolites in crossbred beef cattle
topic candidate genes
crossbred beef cattle
functional enrichment analyses
metabolomics
single-step GBLUP
url https://www.frontiersin.org/article/10.3389/fgene.2020.538600/full
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