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

N1 - © 2024. The Author(s).

PY - 2024

Y1 - 2024

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

U2 - 10.1038/s41598-024-65538-8

DO - 10.1038/s41598-024-65538-8

M3 - Journal article

C2 - 38926497

VL - 14

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 14738

ER -