Integrating genome‐ and transcriptome‐wide association studies to uncover the host–microbiome interactions in bovine rumen methanogenesis

Abstract The ruminal microbiota generates biogenic methane in ruminants. However, the role of host genetics in modifying ruminal microbiota‐mediated methane emissions remains mysterious, which has severely hindered the emission control of this notorious greenhouse gas. Here, we uncover the host gene...

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Main Authors: Wei Wang, Zhenyu Wei, Zhuohui Li, Jianrong Ren, Yanliang Song, Jingyi Xu, Anguo Liu, Xinmei Li, Manman Li, Huimei Fan, Liangliang Jin, Zhannur Niyazbekova, Wen Wang, Yuanpeng Gao, Yu Jiang, Junhu Yao, Fuyong Li, Shengru Wu, Yu Wang
Format: Article
Language:English
Published: Wiley 2024-10-01
Series:iMeta
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Online Access:https://doi.org/10.1002/imt2.234
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author Wei Wang
Zhenyu Wei
Zhuohui Li
Jianrong Ren
Yanliang Song
Jingyi Xu
Anguo Liu
Xinmei Li
Manman Li
Huimei Fan
Liangliang Jin
Zhannur Niyazbekova
Wen Wang
Yuanpeng Gao
Yu Jiang
Junhu Yao
Fuyong Li
Shengru Wu
Yu Wang
author_facet Wei Wang
Zhenyu Wei
Zhuohui Li
Jianrong Ren
Yanliang Song
Jingyi Xu
Anguo Liu
Xinmei Li
Manman Li
Huimei Fan
Liangliang Jin
Zhannur Niyazbekova
Wen Wang
Yuanpeng Gao
Yu Jiang
Junhu Yao
Fuyong Li
Shengru Wu
Yu Wang
author_sort Wei Wang
collection DOAJ
description Abstract The ruminal microbiota generates biogenic methane in ruminants. However, the role of host genetics in modifying ruminal microbiota‐mediated methane emissions remains mysterious, which has severely hindered the emission control of this notorious greenhouse gas. Here, we uncover the host genetic basis of rumen microorganisms by genome‐ and transcriptome‐wide association studies with matched genome, rumen transcriptome, and microbiome data from a cohort of 574 Holstein cattle. Heritability estimation revealed that approximately 70% of microbial taxa had significant heritability, but only 43 genetic variants with significant association with 22 microbial taxa were identified through a genome‐wide association study (GWAS). In contrast, the transcriptome‐wide association study (TWAS) of rumen microbiota detected 28,260 significant gene–microbe associations, involving 210 taxa and 4652 unique genes. On average, host genetic factors explained approximately 28% of the microbial abundance variance, while rumen gene expression explained 43%. In addition, we highlighted that TWAS exhibits a strong advantage in detecting gene expression and phenotypic trait associations in direct effector organs. For methanogenic archaea, only one significant signal was detected by GWAS, whereas the TWAS obtained 1703 significant associated host genes. By combining multiple correlation analyses based on these host TWAS genes, rumen microbiota, and volatile fatty acids, we observed that substrate hydrogen metabolism is an essential factor linking host–microbe interactions in methanogenesis. Overall, these findings provide valuable guidelines for mitigating methane emissions through genetic regulation and microbial management strategies in ruminants.
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spelling doaj-art-208bae13a0de4895bf019bcf63da64c42025-08-20T01:48:04ZengWileyiMeta2770-596X2024-10-0135n/an/a10.1002/imt2.234Integrating genome‐ and transcriptome‐wide association studies to uncover the host–microbiome interactions in bovine rumen methanogenesisWei Wang0Zhenyu Wei1Zhuohui Li2Jianrong Ren3Yanliang Song4Jingyi Xu5Anguo Liu6Xinmei Li7Manman Li8Huimei Fan9Liangliang Jin10Zhannur Niyazbekova11Wen Wang12Yuanpeng Gao13Yu Jiang14Junhu Yao15Fuyong Li16Shengru Wu17Yu Wang18Department of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Nutrition and Environmental Health College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Clinical Veterinary College of Veterinary Medicine Northwest A&F University Yangling ChinaDepartment of Animal Nutrition and Environmental Health College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaSchool of Ecology and Environment Faculty of Life Sciences and Medicine Northwestern Polytechnical University Xi'an ChinaDepartment of Clinical Veterinary College of Veterinary Medicine Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Nutrition and Environmental Health College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Science and Technology College of Animal Sciences Zhejiang University Hangzhou ChinaDepartment of Animal Nutrition and Environmental Health College of Animal Science and Technology Northwest A&F University Yangling ChinaDepartment of Animal Genetics Breeding and Reproduction, College of Animal Science and Technology Northwest A&F University Yangling ChinaAbstract The ruminal microbiota generates biogenic methane in ruminants. However, the role of host genetics in modifying ruminal microbiota‐mediated methane emissions remains mysterious, which has severely hindered the emission control of this notorious greenhouse gas. Here, we uncover the host genetic basis of rumen microorganisms by genome‐ and transcriptome‐wide association studies with matched genome, rumen transcriptome, and microbiome data from a cohort of 574 Holstein cattle. Heritability estimation revealed that approximately 70% of microbial taxa had significant heritability, but only 43 genetic variants with significant association with 22 microbial taxa were identified through a genome‐wide association study (GWAS). In contrast, the transcriptome‐wide association study (TWAS) of rumen microbiota detected 28,260 significant gene–microbe associations, involving 210 taxa and 4652 unique genes. On average, host genetic factors explained approximately 28% of the microbial abundance variance, while rumen gene expression explained 43%. In addition, we highlighted that TWAS exhibits a strong advantage in detecting gene expression and phenotypic trait associations in direct effector organs. For methanogenic archaea, only one significant signal was detected by GWAS, whereas the TWAS obtained 1703 significant associated host genes. By combining multiple correlation analyses based on these host TWAS genes, rumen microbiota, and volatile fatty acids, we observed that substrate hydrogen metabolism is an essential factor linking host–microbe interactions in methanogenesis. Overall, these findings provide valuable guidelines for mitigating methane emissions through genetic regulation and microbial management strategies in ruminants.https://doi.org/10.1002/imt2.234GWASHolstein cattlehost geneticsmethanogenesisrumen microbiotaTWAS
spellingShingle Wei Wang
Zhenyu Wei
Zhuohui Li
Jianrong Ren
Yanliang Song
Jingyi Xu
Anguo Liu
Xinmei Li
Manman Li
Huimei Fan
Liangliang Jin
Zhannur Niyazbekova
Wen Wang
Yuanpeng Gao
Yu Jiang
Junhu Yao
Fuyong Li
Shengru Wu
Yu Wang
Integrating genome‐ and transcriptome‐wide association studies to uncover the host–microbiome interactions in bovine rumen methanogenesis
iMeta
GWAS
Holstein cattle
host genetics
methanogenesis
rumen microbiota
TWAS
title Integrating genome‐ and transcriptome‐wide association studies to uncover the host–microbiome interactions in bovine rumen methanogenesis
title_full Integrating genome‐ and transcriptome‐wide association studies to uncover the host–microbiome interactions in bovine rumen methanogenesis
title_fullStr Integrating genome‐ and transcriptome‐wide association studies to uncover the host–microbiome interactions in bovine rumen methanogenesis
title_full_unstemmed Integrating genome‐ and transcriptome‐wide association studies to uncover the host–microbiome interactions in bovine rumen methanogenesis
title_short Integrating genome‐ and transcriptome‐wide association studies to uncover the host–microbiome interactions in bovine rumen methanogenesis
title_sort integrating genome and transcriptome wide association studies to uncover the host microbiome interactions in bovine rumen methanogenesis
topic GWAS
Holstein cattle
host genetics
methanogenesis
rumen microbiota
TWAS
url https://doi.org/10.1002/imt2.234
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