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Comment
. 2018 Apr 17;115(16):E3601-E3603.
doi: 10.1073/pnas.1802071115. Epub 2018 Mar 27.

Genetic variation in VAC14 is associated with bacteremia secondary to diverse pathogens in African children

James J Gilchrist  1   2 , Alexander J Mentzer  3 , Anna Rautanen  3 , Matti Pirinen  4 , Salim Mwarumba  5 , Patricia Njuguna  5 , Neema Mturi  5 ; Wellcome Trust Case-Control Consortium 2; Kenyan Bacteraemia Study Group; Thomas N Williams  5   6 , J Anthony G Scott  5   7 , Adrian V S Hill  3   8
Collaborators, Affiliations
Comment

Genetic variation in VAC14 is associated with bacteremia secondary to diverse pathogens in African children

James J Gilchrist et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
rs8060947 and major causes of bacteremia in Kenyan children. (A) Cluster plot of rs8060947 (Affymetrix SNP 6.0 chip) in Kenyan children (n = 4,924); minor allele frequency (MAF) = 0.44, Hardy–Weinberg equilibrium (HWE) P = 0.11. (B) rs8060947 association with major causes of bacteremia in Kenyan children; NTS, n = 180, Staphylococcus aureus, n = 175, S. pneumoniae, n = 426, E. coli, n = 151, β-hemolytic Streptococci, n = 146, Haemophilus influenza type b, n = 128, Acinetobacter species, n = 130. Log-transformed ORs and 95% CIs of rs8060947 association (additive model) are calculated by multinomial logistic regression, including four principal components of genome-wide genotyping data to account for population structure. (C) Posterior probabilities of models of association at rs8060947: NULL, no association with any pathogen; REL, related effects ∼ N(0,0.22) across all pathogens (correlation is ρ=0.96); SAME, the same effect ∼ N(0,0.22) across all pathogens (correlation is ρ = 1); TOP, a nonzero effect in bacteremia secondary to nontyphoidal Salmonella, E. coli, S. pneumoniae, and Acinetobacter species alone; this model (highlighted in red) is the most probable (Bayes factor c.f. NULL = 14). Genotype and phenotype data are derived from Rautanen et al. (6). Methods are as described in Rautanen et al. (6).
Fig. 2.
Fig. 2.
Association plot of bacteremia susceptibility at the VAC14 locus. SNPs are colored according to strength of linkage disequilibrium (r2) to rs8060947. Association statistics are calculated using an additive model including bacteremia cases secondary to NTS, E. coli, S. pneumoniae, and Acinetobacter species (n = 887) and shared, healthy controls (n = 2,677). rs8044133 is imputed (imputation information score = 0.996), MAF = 0.47, with no evidence of departure from HWE (P = 0.73). Common (MAF > 0.05), well-imputed SNPs (imputation information score > 0.4), with no evidence for departure from HWE (P > 1 × 10−10) were included in the analysis. Association statistics are calculated by logistic regression, including four principal components of genome-wide genotyping data to account for population structure. Genotype and phenotype data are derived from Rautanen et al. (6). Methods are as described in Rautanen et al. (6).
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