PMID- 33663837 OWN - NLM STAT- MEDLINE DCOM- 20210426 LR - 20210426 IS - 1525-3198 (Electronic) IS - 0022-0302 (Linking) VI - 104 IP - 5 DP - 2021 May TI - Structural equation modeling for unraveling the multivariate genomic architecture of milk proteins in dairy cattle. PG - 5705-5718 LID - S0022-0302(21)00183-1 [pii] LID - 10.3168/jds.2020-18321 [doi] AB - The aims of this study were to investigate potential functional relationships among milk protein fractions in dairy cattle and to carry out a structural equation model (SEM) GWAS to provide a decomposition of total SNP effects into direct effects and effects mediated by traits that are upstream in a phenotypic network. To achieve these aims, we first fitted a mixed Bayesian multitrait genomic model to infer the genomic correlations among 6 milk nitrogen fractions [4 caseins (CN), namely kappa-, beta-, alpha(S1)-, and alpha(S2)-CN, and 2 whey proteins, namely beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA)], in a population of 989 Italian Brown Swiss cows. Animals were genotyped with the Illumina BovineSNP50 Bead Chip v.2 (Illumina Inc.). A Bayesian network approach using the max-min hill-climbing (MMHC) algorithm was implemented to model the dependencies or independence among traits. Strong and negative genomic correlations were found between beta-CN and alpha(S1)-CN (-0.706) and between beta-CN and kappa-CN (-0.735). The application of the MMHC algorithm revealed that kappa-CN and beta-CN seemed to directly or indirectly influence all other milk protein fractions. By integrating multitrait model GWAS and SEM-GWAS, we identified a total of 127 significant SNP for kappa-CN, 89 SNP for beta-CN, 30 SNP for alpha(S1)-CN, and 14 SNP for alpha(S2)-CN (mostly shared among CN and located on Bos taurus autosome 6) and 15 SNP for beta-LG (mostly located on Bos taurus autosome 11), whereas no SNP passed the significance threshold for alpha-LA. For the significant SNP, we assessed and quantified the contribution of direct and indirect paths to total marker effect. Pathway analyses confirmed that common regulatory mechanisms (e.g., energy metabolism and hormonal and neural signals) are involved in the control of milk protein synthesis and metabolism. The information acquired might be leveraged for setting up optimal management and selection strategies aimed at improving milk quality and technological characteristics in dairy cattle. CI - Copyright (c) 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved. FAU - Pegolo, Sara AU - Pegolo S AD - Department of Agronomy, Food Natural Resources, Animals and Environment, University of Padua, 35020 Legnaro (PD), Italy. Electronic address: sara.pegolo@unipd.it. FAU - Yu, Haipeng AU - Yu H AD - Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg 24061. FAU - Morota, Gota AU - Morota G AD - Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg 24061. FAU - Bisutti, Vittoria AU - Bisutti V AD - Department of Agronomy, Food Natural Resources, Animals and Environment, University of Padua, 35020 Legnaro (PD), Italy. FAU - Rosa, Guilherme J M AU - Rosa GJM AD - Department of Animal and Dairy Sciences, University of Wisconsin, Madison 53706; Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison 53792. FAU - Bittante, Giovanni AU - Bittante G AD - Department of Agronomy, Food Natural Resources, Animals and Environment, University of Padua, 35020 Legnaro (PD), Italy. FAU - Cecchinato, Alessio AU - Cecchinato A AD - Department of Agronomy, Food Natural Resources, Animals and Environment, University of Padua, 35020 Legnaro (PD), Italy. LA - eng PT - Journal Article DEP - 20210302 PL - United States TA - J Dairy Sci JT - Journal of dairy science JID - 2985126R RN - 0 (Caseins) RN - 0 (Milk Proteins) SB - IM MH - Animals MH - Bayes Theorem MH - *Caseins/genetics MH - Cattle/genetics MH - Female MH - Genomics MH - Latent Class Analysis MH - *Milk Proteins OTO - NOTNLM OT - Bayesian network OT - cattle OT - genome-wide association analysis OT - milk proteins OT - pathway EDAT- 2021/03/06 06:00 MHDA- 2021/04/27 06:00 CRDT- 2021/03/05 05:45 PHST- 2020/02/06 00:00 [received] PHST- 2020/12/31 00:00 [accepted] PHST- 2021/03/06 06:00 [pubmed] PHST- 2021/04/27 06:00 [medline] PHST- 2021/03/05 05:45 [entrez] AID - S0022-0302(21)00183-1 [pii] AID - 10.3168/jds.2020-18321 [doi] PST - ppublish SO - J Dairy Sci. 2021 May;104(5):5705-5718. doi: 10.3168/jds.2020-18321. Epub 2021 Mar 2.