Polygenic risk prediction: why and when out-of-sample prediction R2 can exceed SNP-based heritability.

In polygenic score (PGS) analysis, the coefficient of determination (R2) is a key statistic to evaluate efficacy. R2 is the proportion of phenotypic variance explained by the PGS, calculated in a cohort that is independent of the genome-wide association study (GWAS) that provided estimates of allelic effect sizes. The SNP-based heritability (hSNP2, the proportion of total phenotypic variances attributable to all common SNPs) is the theoretical upper limit of the out-of-sample prediction R2. However, in real data analyses R2 has been reported to exceed hSNP2, which occurs in parallel with the observation that hSNP2 estimates tend to decline as the number of cohorts being meta-analyzed increases. Here, we quantify why and when these observations are expected. Using theory and simulation, we show that if heterogeneities in cohort-specific hSNP2 exist, or if genetic correlations between cohorts are less than one, hSNP2 estimates can decrease as the number of cohorts being meta-analyzed increases. We derive conditions when the out-of-sample prediction R2 will be greater than hSNP2 and show the validity of our derivations with real data from a binary trait (major depression) and a continuous trait (educational attainment). Our research calls for a better approach to integrating information from multiple cohorts to address issues of between-cohort heterogeneity.

Cross-ancestry analyses identify new genetic loci associated with 25-hydroxyvitamin D.

Vitamin D status-a complex trait influenced by environmental and genetic factors-is tightly associated with skin colour and ancestry. Yet very few studies have investigated the genetic underpinnings of vitamin D levels across diverse ancestries, and the ones that have, relied on small sample sizes, resulting in inconclusive results. Here, we conduct genome-wide association studies (GWAS) of 25 hydroxyvitamin D (25OHD)-the main circulating form of vitamin D-in 442,435 individuals from four broad genetically-determined ancestry groups represented in the UK Biobank: European (N = 421,867), South Asian (N = 9,983), African (N = 8,306) and East Asian (N = 2,279). We identify a new genetic determinant of 25OHD (rs146759773) in individuals of African ancestry, which was not detected in previous analysis of much larger European cohorts due to low minor allele frequency. We show genome-wide significant evidence of dominance effects in 25OHD that protect against vitamin D deficiency. Given that key events in the synthesis of 25OHD occur in the skin and are affected by pigmentation levels, we conduct GWAS of 25OHD stratified by skin colour and identify new associations. Lastly, we test the interaction between skin colour and variants associated with variance in 25OHD levels and identify two loci (rs10832254 and rs1352846) whose association with 25OHD differs in individuals of distinct complexions. Collectively, our results provide new insights into the complex relationship between 25OHD and skin colour and highlight the importance of diversity in genomic studies. Despite the much larger rates of vitamin D deficiency that we and others report for ancestry groups with dark skin (e.g., South Asian), our study highlights the importance of considering ancestral background and/or skin colour when assessing the implications of low vitamin D.

Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration.

While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.

Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling.

BACKGROUND: Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) to identify risk-associated variants are needed. OBJECTIVE: We sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. METHODS: We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n = 46,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations. RESULTS: We tested the association between asthma and 17,190 genes that were found to have cis- and/or trans-eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1, TINF2, and SAFB). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3, USMG5, P2RY13, and P2RY14, which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14-purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively-were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs. CONCLUSION: We identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs.

Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016.

With international travel, Zika virus (ZIKV) is introduced to Europe regularly. A country's ability to robustly detect ZIKV introduction and local transmission is important to minimise the risk for a ZIKV outbreak. Therefore, sufficient expertise and diagnostic capacity and capability are required in European laboratories. To assess the capacity, quality, operational specifics (guidelines and algorithms), technical and interpretation issues and other possible difficulties that were related to ZIKV diagnostics in European countries, a questionnaire was conducted among national reference laboratories in 30 countries in the European Union/European Economic Area (EU/EEA) in May 2016. While the coverage and capacity of ZIKV diagnostics in the EU/EEA national reference laboratories were found to be adequate, the assessment of the quality and needs indicated several crucial points of improvement that will need support at national and EU/EEA level to improve ZIKV preparedness, response and EU/EEA ZIKV surveillance activities.

Large Sequence Diversity within the Biosynthesis Locus and Common Biochemical Features of Campylobacter coli Lipooligosaccharides.

UNLABELLED: Despite the importance of lipooligosaccharides (LOSs) in the pathogenicity of campylobacteriosis, little is known about the genetic and phenotypic diversity of LOS in Campylobacter coli In this study, we investigated the distribution of LOS locus classes among a large collection of unrelated C. coli isolates sampled from several different host species. Furthermore, we paired C. coli genomic information and LOS chemical composition for the first time to investigate possible associations between LOS locus class sequence diversity and biochemical heterogeneity. After identifying three new LOS locus classes, only 85% of the 144 isolates tested were assigned to a class, suggesting higher genetic diversity than previously thought. This genetic diversity is at the basis of a completely unexplored LOS structural heterogeneity. Mass spectrometry analysis of the LOSs of nine isolates, representing four different LOS classes, identified two features distinguishing C. coli LOS from that of Campylobacter jejuni 2-Amino-2-deoxy-d-glucose (GlcN)-GlcN disaccharides were present in the lipid A backbone, in contrast to the ß-1'-6-linked 3-diamino-2,3-dideoxy-d-glucopyranose (GlcN3N)-GlcN backbone observed in C. jejuni Moreover, despite the fact that many of the genes putatively involved in 3-acylamino-3,6-dideoxy-d-glucose (Quip3NAcyl) were apparently absent from the genomes of various isolates, this rare sugar was found in the outer core of all C. coli isolates. Therefore, regardless of the high genetic diversity of the LOS biosynthesis locus in C. coli, we identified species-specific phenotypic features of C. coli LOS that might explain differences between C. jejuni and C. coli in terms of population dynamics and host adaptation. IMPORTANCE: Despite the importance of C. coli to human health and its controversial role as a causative agent of Guillain-Barré syndrome, little is known about the genetic and phenotypic diversity of C. coli LOSs. Therefore, we paired C. coli genomic information and LOS chemical composition for the first time to address this paucity of information. We identified two species-specific phenotypic features of C. coli LOS, which might contribute to elucidating the reasons behind the differences between C. jejuni and C. coli in terms of population dynamics and host adaptation.

Allergen-induced IL-6 trans-signaling activates γδ T cells to promote type 2 and type 17 airway inflammation.

BACKGROUND: A variant in the IL-6 receptor (IL-6R) gene increases asthma risk and is predicted to decrease IL-6 classic signaling and increase IL-6 trans-signaling. This suggests that inhibition of IL-6 trans-signaling, but not classic signaling, might suppress allergic airway inflammation. OBJECTIVES: We sought to determine whether IL-6 signaling contributes to (1) acute experimental asthma induced by clinically relevant allergens and (2) variation in asthma clinical phenotypes in asthmatic patients. METHODS: Mice were sensitized to house dust mite (HDM) or cockroach at day 0, treated with IL-6R inhibitors at day 13, and challenged with the same allergen at days 14 to 17. End points were measured 3 hours after the final challenge. IL-6 and soluble IL-6 receptor (sIL-6R) expression in induced sputum of asthmatic patients was correlated with asthma clinical phenotypes. RESULTS: Both HDM and cockroach induced a type 2/type 17 cytokine profile and mixed granulocytic inflammation in the airways. Both allergens increased IL-6 expression in the airways, but only cockroach induced sIL-6R expression. Therefore HDM challenge promoted IL-6 classic signaling but not trans-signaling; in this model treatment with anti-IL-6R did not suppress airway inflammation. In contrast, cockroach-induced inflammation involved activation of IL-6 trans-signaling and production of IL-17A by γδ T cells. Anti-IL-6R, selective blockade of sIL-6R, or γδ T-cell deficiency significantly attenuated cockroach-induced inflammation. Asthmatic patients with high airway IL-6 and sIL-6R levels were enriched for the neutrophilic and mixed granulocytic subtypes. CONCLUSION: Experimental asthma associated with both high IL-6 and high sIL-6R levels in the airways is attenuated by treatment with IL-6R inhibitors.

Sialylation of Helicobacter bizzozeronii lipopolysaccharides modulates Toll-like receptor (TLR) 2 mediated response.

Sialic acid in lipopolysaccharides (LPS) of mucosal pathogens is known to be an important virulence factor. Few strains of Helicobacter pylori express sialyl-Lewis-X and we have reported that human and canine Helicobacter bizzozeronii strains express sialyl-lactoseamine in their LPS. However, the role of sialyation of Helicobacter LPS in the interaction with the host cells is still unknown. In this study H. bizzozeronii LPS is shown to activate the TLR2 in a dose and strain dependent manner in the in vitro HEK-293 cells model expressing TLR2, but not the cells expressing TLR4. These results indicate that TLR2 is the specific receptor for H. bizzozzeronii LPS, as previously described for H. pylori. To further explore the role of sialylation of H. bizzozeronii LPS on TLR2 response, H. bizzozeronii Δhbs2 mutant strains deficient in sialyltransferase activity were constructed by homologous recombination. LPS from H. bizzozeronii Δhbs2 strains enhanced the NF-ĸB induction via TLR2 compared to the respective wild types, leading to the conclusion that the sialylation of H. bizzozeronii LPS in wild-type strains may modulate host immune response.

Comparative genomics of unintrogressed Campylobacter coli clades 2 and 3.

BACKGROUND: Campylobacter jejuni and C. coli share a multitude of risk factors associated with human gastrointestinal disease, yet their phylogeny differs significantly. C. jejuni is scattered into several lineages, with no apparent linkage, whereas C. coli clusters into three distinct phylogenetic groups (clades) of which clade 1 has shown extensive genome-wide introgression with C. jejuni, yet the other two clades (2 and 3) have less than 2% of C. jejuni ancestry. We characterized a C. coli strain (76339) with four novel multilocus sequence type alleles (ST-5088) and having the capability to express gamma-glutamyltranspeptidase (GGT); an accessory feature in C. jejuni. Our aim was to further characterize unintrogressed C. coli clades 2 and 3, using comparative genomics and with additional genome sequences available, to investigate the impact of horizontal gene transfer in shaping the accessory and core gene pools in unintrogressed C. coli. RESULTS: Here, we present the first fully closed C. coli clade 3 genome (76339). The phylogenomic analysis of strain 76339, revealed that it belonged to clade 3 of unintrogressed C. coli. A more extensive respiratory metabolism among unintrogressed C. coli strains was found compared to introgressed C. coli (clade 1). We also identified other genes, such as serine proteases and an active sialyltransferase in the lipooligosaccharide locus, not present in C. coli clade 1 and we further propose a unique scenario for the evolution of Campylobacter ggt. CONCLUSIONS: We propose new insights into the evolution of the accessory genome of C. coli clade 3 and C. jejuni. Also, in silico analysis of the gene content revealed that C. coli clades 2 and 3 have genes associated with infection, suggesting they are a potent human pathogen, and may currently be underreported in human infections due to niche separation.

Genome analysis of Campylobacter jejuni strains isolated from a waterborne outbreak.

BACKGROUND: Waterborne Campylobacter jejuni outbreaks are common in the Nordic countries, and PFGE (pulsed field gel electrophoresis) remains the genotyping method of choice in outbreak investigations. However, PFGE cannot assess the clonal relationship between isolates, leading to difficulties in molecular epidemiological investigations. Here, we explored the applicability of whole genome sequencing to outbreak investigation by re-analysing three C. jejuni strains (one isolated from water and two from patients) from an earlier resolved Finnish waterborne outbreak from the year 2000. RESULTS: One of the patient strains had the same PFGE profile, as well as an identical overall gene synteny and three polymorphisms in comparison with the water strain. However, the other patient isolate, which showed only minor differences in the PFGE pattern relative to the water strain, harboured several polymorphisms as well as rearrangements in the integrated element CJIE2. We reconstructed the genealogy of these strains with ClonalFrame including in the analysis four C. jejuni isolated from chicken in 2012 having the same PFGE profile and sequence type as the outbreak strains. The three outbreak strains exhibited a paraphyletic relationship, implying that the drinking water from 2000 was probably contaminated with at least two different, but related, C. jejuni strains. CONCLUSIONS: Our results emphasize the capability of whole genome sequencing to unambiguously resolve the clonal relationship between isolates of C. jejuni in an outbreak situation and evaluate the diversity of the C. jejuni population.

Genomic variation between Campylobacter jejuni isolates associated with milk-borne-disease outbreaks.

Bacterial genome sequencing has led to the development of new approaches for the analysis of food-borne epidemics and the exploration of the relatedness of outbreak-associated isolates and their separation from nonassociated isolates. Using Illumina technology, we sequenced a total of six isolates (two from patients, two from raw bulk milk, and two from dairy cattle) associated with a milk-borne Campylobacter jejuni outbreak in a farming family and compared their genomes. These isolates had identical pulsed-field gel electrophoresis (PFGE) types, and their multilocus sequence typing (MLST) type was ST-50. We used the Ma_1 isolate (milk) as the reference, and its genome was assembled and tentatively ordered using the C. jejuni NCTC 11168 genome as the scaffold. Using whole-genome MLST (wgMLST), we identified a total of three single-nucleotide polymorphisms (SNPs) and differences in poly(G or C) or poly(A or T) tracts in 12 loci among the isolates. Several new alleles not present in the database were detected. In contrast, the sequences of the unassociated C. jejuni strains P14 and 1-12S (both ST-50) differed by 420 to 454 alleles from the epidemic-associated isolates. We found that the fecal contamination of bulk tank milk occurred by highly related sequence variants of C. jejuni, which are reflected as SNPs and differences in the length of the poly(A or T) tracts. Poly(G or C) tracts are reversibly variable and are thus unstable markers for comparison. Further, unrelated strains of ST-50 were clearly separated from the outbreak-associated isolates, indicating that wgMLST is an excellent tool for analysis. In addition, other useful data related to the genes and genetic systems of the isolates were obtained.

Safety and efficacy of a feed additive consisting of inactivated selenised yeast (Saccharomyces cerevisiae CCTCC M 2022402) for all animal species (Phytobiotics Futterzusatzstoffe GmbH).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of the selenised yeast (inactivated) Saccharomyces cerevisiae CCTCC M 2022402 (Plexomin® Se 3000, available in two forms: 'granules' and 'micro') as a nutritional feed additive for all animal species. Based on a tolerance-efficacy trial, the FEEDAP Panel concluded that the additive is safe for chickens for fattening at proposed conditions of use and this conclusion can be extrapolated to all animal species. In the absence of deposition data in all animal species and products, the FEEDAP Panel cannot conclude on the safety for the consumer. Plexomin® Se 3000 (granules) is dust-free; therefore, the exposure through inhalation is unlikely. Plexomin® Se 3000 (micro) presents a risk by inhalation. Both forms of the additive (granules and micro) are considered as respiratory sensitisers. Due to the lack of data, no conclusions can be drawn on the dermal and eye irritation potential of Plexomin® Se 3000 (granules). Plexomin® Se 3000 (micro) is not irritant to the skin and the eyes. No conclusions can be drawn on the potential of both forms of the additive to be dermal sensitisers. The use of the additive in animal nutrition is considered safe for the environment. The additive is an efficacious source of selenium in feedingstuffs for all animal species.

Assessment of the feed additive consisting of Levilactobacillus brevis DSM 21982 for all animal species for the renewal of its authorisation (Marigot Ltd T/A Celtic Sea Minerals).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Levilactobacillus brevis DSM 21982 as a technological feed additive, silage additive, for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The Panel concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the additive should be considered as a skin and respiratory sensitiser. No conclusions can be drawn on the eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lacticaseibacillus paracasei ATCC PTA-6135 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of Lacticaseibacillus paracasei ATCC PTA-6135 as a technological additive (functional group: silage additive) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the active agent L. paracasei ATCC PTA-6135 remains safe for all animal species, consumers and the environment. Regarding user safety, the panel concluded that owing to the nature of the additive, L. paracasei ATCC PTA-6135 should be considered a potential skin and respiratory sensitiser, and any exposure through the skin and respiratory tract is considered a risk. In the absence of data, no conclusion could be drawn on the eye irritation potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Limosilactobacillus fermentumNCIMB 30169 for all animal species for the renewal of its authorisation (Microferm Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application of renewal of Limosilactobacillus fermentum NCIMB 30169 as a technological feed additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers, and the environment. Regarding user safety, the additive should be considered a skin and respiratory sensitiser. No conclusions can be drawn on the eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lentilactobacillus buchneriATCC PTA-6138 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lentilactobacillus buchneri ATCC PTA-6138 as a technological additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the additive should be considered as a skin and respiratory sensitiser. No conclusions could be drawn on the eye irritancy potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lentilactobacillus buchneriATCC PTA-2494 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lentilactobacillus buchneri ATCC PTA-2494 as a technological additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the Panel considers that any exposure through skin and respiratory tract is considered a risk. The Panel cannot conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lactiplantibacillus plantarum ATCC PTA-6139 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) ATCC PTA-6139 as a technological additive (functional group: silage additive) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the Panel concluded that owing to the nature of the additive, Lactiplantibacillus plantarum ATCC PTA-6139 should be considered a potential skin and respiratory sensitiser, and that any exposure through the skin and respiratory tract is considered a risk. The Panel could not conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lactiplantibacillus plantarum DSM 18112 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) DSM 18112 as a technological additive (functional group: silage additive) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the Panel concluded that owing to the nature of the additive, Lactiplantibacillus plantarum DSM 18112 should be considered a potential skin and respiratory sensitiser, and that any exposure through the skin and respiratory tract is considered a risk. The Panel could not conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Assessment of the feed additive consisting of Lactiplantibacillus plantarum DSM 18114 for all animal species for the renewal of its authorisation (Pioneer Hi-Bred International, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) DSM 18114 as a technological additive (functional group: silage additive) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumer and the environment. Regarding user safety, the Panel concluded that owing to the nature of the additive, Lactiplantibacillus plantarum DSM 18114 should be considered a potential skin and respiratory sensitiser, and that any exposure through the skin and respiratory tract is considered a risk. The Panel could not conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.