Dataset Information

Replication of gene polymorphisms associated with periodontitis-related traits in an elderly cohort: the Washington Heights/Inwood Community Aging Project Ancillary Study of Oral Health.

ABSTRACT:

Aim

We sought to replicate findings from published genome-wide association studies (GWAS), linking specific candidate gene loci with periodontitis-related clinical/microbial traits.

Materials and methods

In the published GWAS, a total of 2196 single nucleotide polymorphisms associated with periodontitis-related traits at a p ≤ 5 × 10^-6 and mapped to 136 gene loci. The replication cohort included 1124 individuals, 65-98 years old (67% female, 45% Hispanic, 30% Black, 23% White) with available genome-wide genotypes and full-mouth periodontal status. Microbial profiles using checkerboard DNA-DNA hybridization and 16SrRNA sequencing were available from 912 and 739 participants, respectively.

Results

Using gene-specific p-values after linkage disequilibrium pruning, the following gene/phenotype associations replicated successfully: CLEC19A with edentulism and %teeth with pocket depth (PD) ≥4 mm; IL37, HPVC1, TRPS1, ABHD12B, LDLRAD4 (C180rF1), TGM3, and GRK5 with %teeth with PD ≥4 mm; DAB2IP with presence of PD ≥6 mm; KIAA1715(LNPK), ROBO2, RAB28, LINC01017, NELL1, LDLRAD4(C18orF1), and CRYBB2P1 with %teeth with clinical attachment level (CAL) ≥3 mm; RUNX2 and LAMA2 with %teeth with CAL ≥5 mm; and KIAA1715(LNPK) with high colonization by Aggregatibacter actinomycetemcomitans. In addition, CLEC19A, IQSEC1, and EMR1 associated with microbial abundance based on checkerboard data, LBP and NCR2 with abundance based on sequencing data, and NCR2 with microbial diversity based on sequencing data.

Conclusions

Several gene loci identified in published GWAS as associated with periodontitis-related phenotypes replicated successfully in an elderly cohort.

SUBMITTER: Yang T

PROVIDER: S-EPMC9012699 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Replication of gene polymorphisms associated with periodontitis-related traits in an elderly cohort: the Washington Heights/Inwood Community Aging Project Ancillary Study of Oral Health.

Yang Teresa T Cheng Bin B Noble James M JM Reitz Christiane C Papapanou Panos N PN

Journal of clinical periodontology 20220316 5

<h4>Aim</h4>We sought to replicate findings from published genome-wide association studies (GWAS), linking specific candidate gene loci with periodontitis-related clinical/microbial traits.<h4>Materials and methods</h4>In the published GWAS, a total of 2196 single nucleotide polymorphisms associated with periodontitis-related traits at a p ≤ 5 × 10<sup>-6</sup> and mapped to 136 gene loci. The replication cohort included 1124 individuals, 65-98 years old (67% female, 45% Hispanic, 30% Black, 23% ...[more]

PMID: 35179257

Similar Datasets

Project description:This track is produced as part of the ENCODE Project. This track shows genome-wide assessment of DNA replication timing in cell lines using the sequencing-based "Repli-seq" methodology (see below). Replication timing is known to be an important feature for epigenetic control of gene expression that usually operates at a higher-order level than at the level of specific genes. For each experiment (cell line, replicate), replication timing was ascertained by the isolation and sequencing of newly replicated DNA from six cell cycle fractions: G1/G1b, S1, S2, S3, S4, G2 (six fraction profile). Replication patterns are visualized as a continuous function based on sequencing tag density (Percentage-normalized Signal) and as a wavelet-smoothed transform of the six fraction profile (Wavelet-smoothed Signal). Replication peaks corresponding to replication initiation zones (Peaks) and valleys corresponding to replication termination zones (Valleys) were determined from local maxima and minima, respectively, in the wavelet-smoothed signal data. A measure of relative copy number at each genomic location (Summed Densities) was determined by summing the normalized tag density values of each cell cycle fraction at that location (equals one replicated genome equivalent). For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Cells were grown according to the approved ENCODE cell culture protocols. Repli-seq was performed as described by Hansen et al. (2010). Briefly, newly replicated DNA was labeled in vivo with a pulse of 5-bromo-2-deoxyuridine (BrdU), cells were fractionated into six different parts of the cell cycle by flow cytometry according to DNA content, cell cycle fractionated DNA was sonicated and an anti-BrdU monoclonal antibody was used to isolate the newly replicating DNA. Fragment ends were sequenced using the Illumina Genome Analyzer II or HiSeq platforms (36 bp reads). Some experiments (BJ, K562, BG02ES, GM06990) were originally performed and mapped to an earlier version of the human reference genome NCBI36/hg18 (Hansen et al., 2010) and were remapped to the more recent reference genome GRCh37/hg19. Uniquely mapping high-quality reads were mapped to the genome minus the Y chromosome. Replication signals within each six cell cycle fraction were derived from the density of sequence tags mapping within a 50 kb sliding window (stepped 1 kb across the genome); these densities were normalized to 4 million tags per genome. To avoid variation due to copy number or sequence bias, cell cycle-specific replication signals at each location were determined as a percentage of the sum of the six normalized tag density signals (Percentage-normalized Signal). To transform the six fraction replication signals into one track (Wavelet-smoothed Signal), the percentage-normalized signals at each location were used to calculate a weighted average value based on the average DNA content of each fraction according to flow cytometry [higher values correspond to earlier replication; formula=(0.917*G1b)+(0.750*S1)+(0.583*S2)+(0.417*S3)+(0.250*S4)+(0*G2)]. These weighted average data were smoothed by wavelet transformation [J7 level, corresponding to a scale of 128 kb; see Thurman et al. (2007)]. Replication initiation zones were flagged by determining local maxima in the wavelet-smoothed data (Peaks) and, similarly, replication termination zones were flagged by local minima (Valleys). The sum of the 4 million normalized replication tag densities correspond to replication of one genome and can, therefore, be used as a measure of relative genomic copy number (Summed Densities). This is useful for evaluation of unusual replication patterns, such as "biphasic" ones where replication has both early and late components [as described by Hansen et al. (2010)].

Dataset Information

Replication of gene polymorphisms associated with periodontitis-related traits in an elderly cohort: the Washington Heights/Inwood Community Aging Project Ancillary Study of Oral Health.

Aim

Materials and methods

Results

Conclusions

Publications

Replication of gene polymorphisms associated with periodontitis-related traits in an elderly cohort: the Washington Heights/Inwood Community Aging Project Ancillary Study of Oral Health.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets