Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health

Evelina Stankevic; Timo Kern; Dmitrii Borisevich; Casper Sahl Poulsen; Anne Lundager Madsen; Tue Haldor Hansen; Anna Jonsson; Mikkel Schubert; Nikoline Nygaard; Trine Nielsen; Daniel Belstrøm; Tarunveer S Ahluwalia; Daniel R Witte; Niels Grarup; Manimozhiyan Arumugam; Oluf Pedersen; Torben Hansen

doi:10.1038/s41598-024-65538-8

Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health

Evelina Stankevic
, Timo Kern
, Dmitrii Borisevich
, Casper Sahl Poulsen
, Anne Lundager Madsen
, Tue Haldor Hansen
, Anna Jonsson
, Mikkel Schubert
, Nikoline Nygaard
, Trine Nielsen
, Daniel Belstrøm
, Tarunveer S Ahluwalia
, Daniel R Witte
, Niels Grarup
, Manimozhiyan Arumugam
, Oluf Pedersen
, Torben Hansen^*

^*Corresponding author for this work

Medicine (Køge)

Research output: Contribution to journal › Article › Research › peer-review

Abstract

The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P < 5 × 10-8). Notably, SNP rs17793860 surpassed our study-wide significance threshold (P < 1.19 × 10-9). Additionally, rs4530093 was linked to bacterial beta diversity (P < 5 × 10-8). Out of these seven SNPs identified, six exerted effects on metabolic traits, including glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol levels, the risk of type 2 diabetes and stroke. Our findings highlight the impact of specific host SNPs on the composition and diversity of the oral bacterial community. Importantly, our results indicate an intricate interplay between host genetics, the oral microbiota, and metabolic health. We emphasize the need for integrative approaches considering genetic, microbial, and metabolic factors.

Original language	English
Article number	14738
Number of pages	11
Journal	Scientific Reports
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41598-024-65538-8
Publication status	Published - 26 Jun 2024

Funding

The ADDITION-PRO study was funded by an unrestricted grant from the European Foundation for the Study of Diabetes/Pfizer for Research into Cardiovascular Disease Risk Reduction in Patients with Diabetes (74550801), by the Danish Council for Strategic Research and by internal research and equipment funds from Steno Diabetes Center Copenhagen and The Novo Nordisk Foundation (grant number NNF18CC0034900).

Funders	Funder number
European Foundation for the Study of Diabetes	74550801
Copenhagen University Hospital - Steno Diabetes Center Copenhagen
Novo Nordisk Foundation	NNF18CC0034900
University of Copenhagen	Hansen Group, Arumugam Group
Copenhagen University Hospital - Steno Diabetes Center Copenhagen	SDCC 3.A Complications

Keywords

Humans
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Female
Microbiota/genetics
Male
Middle Aged
Mouth/microbiology
Adult
RNA, Ribosomal, 16S/genetics
Diabetes Mellitus, Type 2/genetics
Saliva/microbiology
Aged
Host genetics and microbiota interplay
Metabolic disease
Microbiome-genome wide association study
Oral microbiota
Single nucleotide polymorphism
Oral health

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10.1038/s41598-024-65538-8

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Stankevic, E., Kern, T., Borisevich, D., Poulsen, C. S., Madsen, A. L., Hansen, T. H., Jonsson, A., Schubert, M., Nygaard, N., Nielsen, T., Belstrøm, D., Ahluwalia, T. S., Witte, D. R., Grarup, N., Arumugam, M., Pedersen, O., & Hansen, T. (2024). Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health. Scientific Reports, 14(1), Article 14738. https://doi.org/10.1038/s41598-024-65538-8

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title = "Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health",

abstract = "The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P < 5 × 10-8). Notably, SNP rs17793860 surpassed our study-wide significance threshold (P < 1.19 × 10-9). Additionally, rs4530093 was linked to bacterial beta diversity (P < 5 × 10-8). Out of these seven SNPs identified, six exerted effects on metabolic traits, including glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol levels, the risk of type 2 diabetes and stroke. Our findings highlight the impact of specific host SNPs on the composition and diversity of the oral bacterial community. Importantly, our results indicate an intricate interplay between host genetics, the oral microbiota, and metabolic health. We emphasize the need for integrative approaches considering genetic, microbial, and metabolic factors.",

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author = "Evelina Stankevic and Timo Kern and Dmitrii Borisevich and Poulsen, \{Casper Sahl\} and Madsen, \{Anne Lundager\} and Hansen, \{Tue Haldor\} and Anna Jonsson and Mikkel Schubert and Nikoline Nygaard and Trine Nielsen and Daniel Belstr{\o}m and Ahluwalia, \{Tarunveer S\} and Witte, \{Daniel R\} and Niels Grarup and Manimozhiyan Arumugam and Oluf Pedersen and Torben Hansen",

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doi = "10.1038/s41598-024-65538-8",

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Stankevic, E, Kern, T, Borisevich, D, Poulsen, CS, Madsen, AL, Hansen, TH, Jonsson, A, Schubert, M, Nygaard, N, Nielsen, T, Belstrøm, D, Ahluwalia, TS, Witte, DR, Grarup, N, Arumugam, M, Pedersen, O & Hansen, T 2024, 'Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health', Scientific Reports, vol. 14, no. 1, 14738. https://doi.org/10.1038/s41598-024-65538-8

TY - JOUR

T1 - Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health

AU - Stankevic, Evelina

AU - Kern, Timo

AU - Borisevich, Dmitrii

AU - Poulsen, Casper Sahl

AU - Madsen, Anne Lundager

AU - Hansen, Tue Haldor

AU - Jonsson, Anna

AU - Schubert, Mikkel

AU - Nygaard, Nikoline

AU - Nielsen, Trine

AU - Belstrøm, Daniel

AU - Ahluwalia, Tarunveer S

AU - Witte, Daniel R

AU - Grarup, Niels

AU - Arumugam, Manimozhiyan

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2024/6/26

Y1 - 2024/6/26

N2 - The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P < 5 × 10-8). Notably, SNP rs17793860 surpassed our study-wide significance threshold (P < 1.19 × 10-9). Additionally, rs4530093 was linked to bacterial beta diversity (P < 5 × 10-8). Out of these seven SNPs identified, six exerted effects on metabolic traits, including glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol levels, the risk of type 2 diabetes and stroke. Our findings highlight the impact of specific host SNPs on the composition and diversity of the oral bacterial community. Importantly, our results indicate an intricate interplay between host genetics, the oral microbiota, and metabolic health. We emphasize the need for integrative approaches considering genetic, microbial, and metabolic factors.

AB - The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P < 5 × 10-8). Notably, SNP rs17793860 surpassed our study-wide significance threshold (P < 1.19 × 10-9). Additionally, rs4530093 was linked to bacterial beta diversity (P < 5 × 10-8). Out of these seven SNPs identified, six exerted effects on metabolic traits, including glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol levels, the risk of type 2 diabetes and stroke. Our findings highlight the impact of specific host SNPs on the composition and diversity of the oral bacterial community. Importantly, our results indicate an intricate interplay between host genetics, the oral microbiota, and metabolic health. We emphasize the need for integrative approaches considering genetic, microbial, and metabolic factors.

KW - Humans

KW - Genome-Wide Association Study

KW - Polymorphism, Single Nucleotide

KW - Female

KW - Microbiota/genetics

KW - Male

KW - Middle Aged

KW - Mouth/microbiology

KW - Adult

KW - RNA, Ribosomal, 16S/genetics

KW - Diabetes Mellitus, Type 2/genetics

KW - Saliva/microbiology

KW - Aged

KW - Host genetics and microbiota interplay

KW - Metabolic disease

KW - Microbiome-genome wide association study

KW - Oral microbiota

KW - Single nucleotide polymorphism

KW - Oral health

U2 - 10.1038/s41598-024-65538-8

DO - 10.1038/s41598-024-65538-8

M3 - Article

C2 - 38926497

SN - 2045-2322

VL - 14

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 14738

ER -

Genome-wide association study identifies host genetic variants influencing oral microbiota diversity and metabolic health

Abstract

Funding

Keywords

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