Article Figures & Data
Figures
- FIG 1
(A to E) Manhattan plots for single nucleotide polymorphisms associated with vaginal microbiome traits. The x axis corresponds to the genomic position, and the y axis shows the −log10 of the P value. The horizontal red line corresponds to the genome-wide significance threshold line corresponds to the genome-wide significance threshold.
- FIG 2
(A to E) Regional association plots of the top genomic loci associated with vaginal microbiome traits. P values (−log10) of the GWAS (solid circles) on the y axis are plotted against the genomic positions of each SNP on the x axis for each microbiome trait. Genes in the region are shown below. The linkage disequilibrium (LD) values (r2) between the lead SNP and the other SNPs are indicated in different colors.
- FIG 3
Heatmap summarizing beta coefficients for the most significant SNPs within 100 kbp of previously reported SNPs. The heatmap on the left represents the direction and magnitude of the coefficients (beta) for the SNPs within 100 kb associated with five vaginal microbiome traits: (A) relative abundance of L. iners, (B) presence of L. crispatus, (C) relative abundance of G. vaginalis, (D) Shannon diversity index, (E) community state type (CST), with CST-IV as the reference. Negative coefficients are shaded in blue, and positive coefficients are shaded in red, with deeper intensity representing the magnitude of the coefficient. The heatmap on the right represents the P value of the corresponding coefficients for SNPs and vaginal microbiome traits (A to E). All associations shown have P values of <0.05. The Bonferroni cutoff for significance is <0.00102, and these P values are shaded yellow to purple. P values of >0.00102 to 0.05 are shaded gray.
Tables
- TABLE 1
Baseline participant characteristics and vaginal microbiome composition overall and stratified by community state typea
- TABLE 2
Top single nucleotide polymorphisms associated with five vaginal microbiome traits
↵a L. crispatus is modeled as presence/absence; L. iners and G. vaginalis are modeled as continuous and quantiles of inverse log-transformed relative abundance, respectively. SNP, single nucleotide polymorphism.
↵b Chr, chromosome.
↵c Gene name is in boldface if the SNP is located within the gene.
↵d A1/A2, allele 1/allele 2.
↵e MAF, minor allele frequency.
↵f SNPs with a P value of <1 × 10−5 for each trait are included in the table.
↵g Reported as odds ratio.
- TABLE 4
Results of disease/phenotype analysis: top phenotypes associated with vaginal microbiome traits
↵a P values are Benjamini-Hochberg adjusted.
FIG S1
(A to E) Q-Q plots for five vaginal microbiome traits measured in 171 Kenyan women. Inspection of Q-Q plots for each microbiome trait evaluated indicate proper control of population stratification. Download FIG S1, TIF file, 0.2 MB.
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TABLE S1
Sensitivity analysis of the top GWAS SNPs adjusting for HIV and HSV-2 status. SNP, single nucleotide polymorphism; Chr, chromosome; A1/A2, allele 1/allele 2. aReported as odds ratio. Download Table S1, DOCX file, 0.01 MB.
Copyright © 2020 Mehta et al.
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TABLE S2
Comparison of top SNPs across vaginal microbiome traits. P values corresponding to the top SNPs identified during single trait analysis are shown in italics. SNPs with P < 3.13 × 10−3 (0.05/16) are shown in boldface. Shannon, Shannon diversity index; CST, community state type. Download Table S2, DOCX file, 0.02 MB.
Copyright © 2020 Mehta et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
FIG S2
(A to E) Regional conditional association plots of the top genomic loci associated with vaginal microbiome traits. P values (−log10) of the GWAS (solid circles) on the y axis are plotted against the genomic positions of each SNP on the x axis for each microbiome trait. Genes in the region are shown below. The linkage disequilibrium (LD) values (r2) between the lead SNP and the other SNPs are indicated in different colors. Download FIG S2, TIF file, 0.9 MB.
Copyright © 2020 Mehta et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
TABLE S3
Analysis of previously reported loci. Note that this is an Excel file. Download Table S3, XLSX file, 0.03 MB.
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TABLE S4
Top genes from gene level analysis for each vaginal microbiome trait. Bonferroni corrected P value, 2.36 × 10−6 (0.05/21,213). Download Table S4, DOCX file, 0.01 MB.
Copyright © 2020 Mehta et al.
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TABLE S5
Count of top single nucleotide polymorphisms (SNPs) by P value threshold for each vaginal microbiome trait. *5.00 × 10−8 is the conventional genome-wide significance level used in genome-wide association studies. 1.49 × 10−7 is the Bonferroni significance level in this study. Download Table S5, DOCX file, 0.01 MB.
Copyright © 2020 Mehta et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
TABLE S6
Power table representing the minimum sample sizes needed to reach Bonferroni significance for each vaginal microbiome trait, expressed at three statistical power settings: 80%, 90%, and 95% power. *Bonferroni significance P value in our study, P = 1.49 × 10−7. **“N Extra” represents the number of samples needed in addition to the current samples in the study. SNP, single nucleotide polymorphism; Chr, chromosome. Download Table S6, DOCX file, 0.02 MB.
Copyright © 2020 Mehta et al.
This content is distributed under the terms of the Creative Commons Attribution 4.0 International license.
DATA SET S1
Final analytic data set GWAS VMB (n = 171). Note that this is an Excel file. Download Data Set S1, XLS file, 0.05 MB.
Copyright © 2020 Mehta et al.
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