Genome-wide association study of periodontal pathogen colonization.
Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom "checkerboard" DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: "high red" and "high orange" bacterial complexes, and "high" Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10(-8)). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10(-6)) of association. All associations reported for "red" and "orange" complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease.
Department of Pediatric Dentistry, School of Dentistry, University of North Carolina-Chapel Hill, 228 Brauer Hall, CB#7450, NC 27599, USA.
K
K
Divaris
K L
KL
Monda
K E
KE
North
A F
AF
Olshan
E M
EM
Lange
K
K
Moss
S P
SP
Barros
J D
JD
Beck
S
S
Offenbacher
D016976:Aggregatibacter actinomycetemcomitans / Q000145:classification / Q000235:genetics; D058491:Bacterial Load; D001439:Bacteroides / Q000145:classification / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D044883:Campylobacter rectus / Q000145:classification / Q000235:genetics; D055113:Chronic Periodontitis / Q000382:microbiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D044783:F-Box Proteins / Q000235:genetics; D005260:Female; D016967:Fusobacterium nucleatum / Q000145:classification / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics; D008297:Male; D054892:Metagenome / Q000235:genetics*; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010519:Periodontium / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000145:classification / Q000235:genetics; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics; D018713:Prevotella intermedia / Q000145:classification / Q000235:genetics; D045242:Prevotella nigrescens / Q000145:classification / Q000235:genetics; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D048373:Treponema denticola / Q000145:classification / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051040:Vesicle-Associated Membrane Protein 3 / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics
C487554:CAMTA1 protein, human; D002135:Calcium-Binding Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; C109137:KCNK1 protein, human; D024683:Potassium Channels, Tandem Pore Domain; C493709:RUNX2 protein, human; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C494946:VAMP3 protein, human; D051040:Vesicle-Associated Membrane Protein 3; C465619:UHRF2 protein, human; D044767:Ubiquitin-Protein Ligases