A multi-tissue atlas of regulatory variants in cattle

Shuli Liu; Yahui Gao; Oriol Canela-Xandri; Sheng Wang; Ying Yu; Wentao Cai; Bingjie Li; Ruidong Xiang; Amanda J. Chamberlain; Erola Pairo-Castineira; Kenton D’Mellow; Konrad Rawlik; Charley Xia; Yuelin Yao; Pau Navarro; Dominique Rocha; Xiujin Li; Ze Yan; Congjun Li; Benjamin D. Rosen; Curtis P. Van Tassell; Paul M. Vanraden; Shengli Zhang; Li Ma; John B. Cole; George E. Liu; Albert Tenesa; Lingzhao Fang

doi:10.1038/s41588-022-01153-5

A multi-tissue atlas of regulatory variants in cattle

Shuli Liu, Yahui Gao, Oriol Canela-Xandri, Sheng Wang, Ying Yu, Wentao Cai, Bingjie Li, Ruidong Xiang, Amanda J. Chamberlain, Erola Pairo-Castineira, Kenton D’Mellow, Konrad Rawlik, Charley Xia, Yuelin Yao, Pau Navarro, Dominique Rocha, Xiujin Li, Ze Yan, Congjun Li, Benjamin D. RosenCurtis P. Van Tassell, Paul M. Vanraden, Shengli Zhang, Li Ma, John B. Cole, George E. Liu^*, Albert Tenesa, Lingzhao Fang

^*Corresponding author for this work

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Abstract

Characterization of genetic regulatory variants acting on livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype–Tissue Expression atlas (CattleGTEx) as part of the pilot phase of the Farm animal GTEx (FarmGTEx) project for the research community based on 7,180 publicly available RNA-sequencing (RNA-seq) samples. We describe the transcriptomic landscape of more than 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multiomics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle.

Original language	English
Pages (from-to)	1438-1447
Number of pages	10
Journal	Nature Genetics
Volume	54
Early online date	11 Aug 2022
DOIs	https://doi.org/10.1038/s41588-022-01153-5
Publication status	Print publication - Sept 2022

Bibliographical note

Keywords

Animals
Cattle/genetics
Gene Expression Regulation
Phenotype
Quantitative Trait Loci/genetics
Sequence Analysis, RNA
Transcriptome/genetics

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NG-AN56393R3_Fang_-_EdVer_1654531276_1_CompletedAccepted author manuscript, 98.6 KBLicence: CC BY-NC

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Liu, S., Gao, Y., Canela-Xandri, O., Wang, S., Yu, Y., Cai, W., Li, B., Xiang, R., Chamberlain, A. J., Pairo-Castineira, E., D’Mellow, K., Rawlik, K., Xia, C., Yao, Y., Navarro, P., Rocha, D., Li, X., Yan, Z., Li, C., ... Fang, L. (2022). A multi-tissue atlas of regulatory variants in cattle. Nature Genetics, 54, 1438-1447. https://doi.org/10.1038/s41588-022-01153-5

@article{d31f490fa916441aa8644c505aba3903,

title = "A multi-tissue atlas of regulatory variants in cattle",

abstract = "Characterization of genetic regulatory variants acting on livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype–Tissue Expression atlas (CattleGTEx) as part of the pilot phase of the Farm animal GTEx (FarmGTEx) project for the research community based on 7,180 publicly available RNA-sequencing (RNA-seq) samples. We describe the transcriptomic landscape of more than 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multiomics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle.",

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author = "Shuli Liu and Yahui Gao and Oriol Canela-Xandri and Sheng Wang and Ying Yu and Wentao Cai and Bingjie Li and Ruidong Xiang and Chamberlain, {Amanda J.} and Erola Pairo-Castineira and Kenton D{\textquoteright}Mellow and Konrad Rawlik and Charley Xia and Yuelin Yao and Pau Navarro and Dominique Rocha and Xiujin Li and Ze Yan and Congjun Li and Rosen, {Benjamin D.} and {Van Tassell}, {Curtis P.} and Vanraden, {Paul M.} and Shengli Zhang and Li Ma and Cole, {John B.} and Liu, {George E.} and Albert Tenesa and Lingzhao Fang",

note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2022",

month = sep,

doi = "10.1038/s41588-022-01153-5",

language = "English",

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Liu, S, Gao, Y, Canela-Xandri, O, Wang, S, Yu, Y, Cai, W, Li, B, Xiang, R, Chamberlain, AJ, Pairo-Castineira, E, D’Mellow, K, Rawlik, K, Xia, C, Yao, Y, Navarro, P, Rocha, D, Li, X, Yan, Z, Li, C, Rosen, BD, Van Tassell, CP, Vanraden, PM, Zhang, S, Ma, L, Cole, JB, Liu, GE, Tenesa, A & Fang, L 2022, 'A multi-tissue atlas of regulatory variants in cattle', Nature Genetics, vol. 54, pp. 1438-1447. https://doi.org/10.1038/s41588-022-01153-5

TY - JOUR

T1 - A multi-tissue atlas of regulatory variants in cattle

AU - Liu, Shuli

AU - Gao, Yahui

AU - Canela-Xandri, Oriol

AU - Wang, Sheng

AU - Yu, Ying

AU - Cai, Wentao

AU - Li, Bingjie

AU - Xiang, Ruidong

AU - Chamberlain, Amanda J.

AU - Pairo-Castineira, Erola

AU - D’Mellow, Kenton

AU - Rawlik, Konrad

AU - Xia, Charley

AU - Yao, Yuelin

AU - Navarro, Pau

AU - Rocha, Dominique

AU - Li, Xiujin

AU - Yan, Ze

AU - Li, Congjun

AU - Rosen, Benjamin D.

AU - Van Tassell, Curtis P.

AU - Vanraden, Paul M.

AU - Zhang, Shengli

AU - Ma, Li

AU - Cole, John B.

AU - Liu, George E.

AU - Tenesa, Albert

AU - Fang, Lingzhao

PY - 2022/9

Y1 - 2022/9

N2 - Characterization of genetic regulatory variants acting on livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype–Tissue Expression atlas (CattleGTEx) as part of the pilot phase of the Farm animal GTEx (FarmGTEx) project for the research community based on 7,180 publicly available RNA-sequencing (RNA-seq) samples. We describe the transcriptomic landscape of more than 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multiomics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle.

AB - Characterization of genetic regulatory variants acting on livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype–Tissue Expression atlas (CattleGTEx) as part of the pilot phase of the Farm animal GTEx (FarmGTEx) project for the research community based on 7,180 publicly available RNA-sequencing (RNA-seq) samples. We describe the transcriptomic landscape of more than 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multiomics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle.

KW - Animals

KW - Cattle/genetics

KW - Gene Expression Regulation

KW - Phenotype

KW - Quantitative Trait Loci/genetics

KW - Sequence Analysis, RNA

KW - Transcriptome/genetics

UR - http://www.scopus.com/inward/record.url?scp=85135833417&partnerID=8YFLogxK

U2 - 10.1038/s41588-022-01153-5

DO - 10.1038/s41588-022-01153-5

M3 - Article

C2 - 35953587

AN - SCOPUS:85135833417

SN - 1061-4036

VL - 54

SP - 1438

EP - 1447

JO - Nature Genetics

JF - Nature Genetics

ER -

A multi-tissue atlas of regulatory variants in cattle

Abstract

Bibliographical note

Keywords

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