Genome-wide study in Germans identifies four novel multiple sclerosis risk genes and confirms already known gene loci.

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Genome-wide association studies (GWAS) successfully identified various chromosomal regions to be associated with multiple sclerosis (MS). The primary aim of this study was to replicate reported associations from GWAS using an exome array in a large German study. German MS cases (n = 4,476) and German controls (n = 5,714) were genotyped using the Illumina HumanExome v1-Chip. Genotype calling was performed with the Illumina Genome Studio(TM) Genotyping Module, followed by zCall. Single-nucleotide polymorphisms (SNPs) in seven regions outside the human leukocyte antigen (HLA) region showed genome-wide significant associations with MS (P values < 5 × 10(-8) ). These associations have been reported previously. In addition, SNPs in three previously reported regions outside the HLA region yielded P values < 10(-5) . The effect of nine SNPs in the HLA region remained (P < 10(-5) ) after adjustment for other significant SNPs in the HLA region. All of these findings have been reported before or are driven by known risk loci. In summary, findings from previous GWAS for MS could be successfully replicated. We conclude that the regions identified in previous GWAS are also associated in the German population. This reassures the need for detailed investigations of the functional mechanisms underlying the replicated associations.

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Objective: Investigation of the origin of a Serratia marcescens outbreak in a neonatal intensive care unit. Design: Retrospective case–control study. Setting: Regional level 3 perinatal center in Germany. Patients: This study included 4 S. marcescens–positive and 19 S. marcescens–negative neonates treated between February 1 and February 26, 2019, in the neonatal intensive care unit. Methods: A case–control study was performed to identify the source of the outbreak. The molecular investigation of S. marcescens isolates collected during the outbreak was performed using pulsed-field gel electrophoresis and next-generation sequencing. Results: The retrospective case–control study showed a significant correlation (P < .0001) between S. marcensens infection or colonization and consumption of donor milk that had tested negative for pathogenic bacteria from a single breast milk donor. Pulsed-field gel electrophoresis and next-generation sequencing retrospectively confirmed an S. marcescens strain isolated from the breast milk of this donor as the possible origin of the initial outbreak. The outbreak was controlled by the implementation of an infection control bundle including a multidisciplinary infection control team, temporary nutrition of infants with formula only and/or their mother’s own milk, repeated screening of all inpatients, strict coat and glove care, process observation, retraining of hand hygiene and continuous monitoring of environmental cleaning procedures. Conclusions: Low-level contaminated raw donor milk can be a source of infection and colonization of preterm infants with S. marcescens even if it tests negative for bacteria.