Genetic variants linked to the phenotypic outcome of invasive disease and carriage of .

can be a human commensal in the upper respiratory tract but is also capable of causing invasive diseases such as meningococcal meningitis and septicaemia. No specific genetic markers have been detected to distinguish carriage from disease isolates. The aim here was to find genetic traits that could be linked to phenotypic outcomes associated with carriage versus invasive disease through a bacterial genome-wide association study (GWAS). In this study, invasive isolates collected in Sweden (=103) and carriage isolates collected at Örebro University, Sweden (=213) 2018-2019 were analysed. The GWAS analysis, treeWAS was applied to single-nucleotide polymorphisms (SNPs), genes and k-mers. One gene and one non-synonymous SNP were associated with invasive disease and seven genes and one non-synonymous SNP were associated with carriage isolates. The gene associated with invasive disease encodes a phage transposase (NEIS1048), and the associated invasive SNP S373C encodes the enzyme N-acetylglucosamine 1-phosphate (GlcNAC 1-P) uridyltransferase. Of the genes associated with carriage isolates, a gene variant of encoding PorB class 3, the genes / and have known functions. The SNP associated with carriage was D33N, encoding a FK506-binding protein (FKBP). K-mers from , and were found to be associated with carriage, while k-mers from and were associated with invasiveness. In the genes , , and , k-mers were found that were associated with both carriage and invasive isolates, indicating that specific variations within these genes could play a role in invasiveness. The data presented here highlight genetic traits that are significantly associated with invasive or carriage across the species population. These traits could prove essential to our understanding of the pathogenicity of and could help to identify future vaccine targets.