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Background   Chlamydia trachomatis  ( Ct ) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide.  Ct  strain-specific differences in clinical trachoma suggest that genetic polymorphisms in  Ct  may contribute to the observed variability in severity of clinical disease.    Methods  Using  Ct  whole genome sequences obtained directly from conjunctival swabs, we studied  Ct  genomic diversity and associations between  Ct  genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa.    Results  All  Ct  sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in  trpA  resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in  tarP  associated with ocular tissue localization. We have identified 21  Ct  non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within  pmpD  (odds ratio, OR = 4.07,  p*  = 0.001) and  tarP  (OR = 0.34,  p*  = 0.009). Eight synonymous SNPs associated with disease severity were found in  yjfH  ( rlmB ) (OR = 0.13,  p*  = 0.037),  CTA0273  (OR = 0.12,  p*  = 0.027),  trmD  (OR = 0.12,  p*  = 0.032),  CTA0744  (OR = 0.12,  p*  = 0.041),  glgA  (OR = 0.10,  p*  = 0.026),  alaS  (OR = 0.10,  p*  = 0.032),  pmpE  (OR = 0.08,  p*  = 0.001) and the intergenic region  CTA0744–CTA0745  (OR = 0.13,  p*  = 0.043).    Conclusions  This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular  Ct  and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular  Ct  pathogenesis and disease transmission.    Electronic supplementary material  The online version of this article (10.1186/s13073-018-0521-x) contains supplementary material, which is available to authorized users.

Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity