Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project.

1. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Authors
Lopera-Maya EA¹
Kurilshikov A¹
van der Graaf A¹
Hu S^{1,

2}
Andreu-Sánchez S¹
Chen L¹
Vila AV^{1,

2}
Gacesa R^{1,

2}
Collij V^{1,

2}
Klaassen MAY^{1,

2}
Bolte LA^{1,

2}
Gois MFB¹
Neerincx PBT¹
Swertz MA¹
Wijmenga C¹
Fu J¹
Zhernakova A¹
Sanna S¹
(18 authors)
2. Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Authors
Hu S^{1,

2}
Vila AV^{1,

2}
Gacesa R^{1,

2}
Sinha T²
Collij V^{1,

2}
Klaassen MAY^{1,

2}
Bolte LA^{1,

2}
Weersma RK²
(8 authors)
3. Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Authors
Harmsen HJM³
(1 author)

ORCIDs linked to this article

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Nature Genetics, 03 Feb 2022, 54(2):143-151
https://doi.org/10.1038/s41588-021-00992-y PMID: 35115690

This article has been corrected. See Nat Genet. 2022 Sep;54(9):1448. This article is based on a previously available preprint.

Abstract

Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10^-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10^-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.

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ABO glycosyltransferase B antigen(UniProt - A0A023W2C2)
Histo-blood group ABO system transferase(UniProt - A0A089QDC1)
ABO glycosyltransferase(UniProt - A0A023W307)
ABO glycosyltransferase(UniProt - A0A060VD92)
ABO glycosyltransferase(UniProt - A0A060VHY2)

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Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project.

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