How 'situational' is judgment in situational judgment tests?

Whereas situational judgment tests (SJTs) have traditionally been conceptualized as low-fidelity simulations with an emphasis on contextualized situation descriptions and context-dependent knowledge, a recent perspective views SJTs as measures of more general domain (context-independent) knowledge. In the current research, we contrasted these 2 perspectives in 3 studies by removing the situation descriptions (i.e., item stems) from SJTs. Across studies, the traditional contextualized SJT perspective was not supported for between 43% and 71% of the items because it did not make a significant difference whether the situation description was included or not for these items. These results were replicated across construct domains, samples, and response instructions. However, there was initial evidence that judgment in SJTs was more situational when (a) items measured job knowledge and skills and (b) response options denoted context-specific rules of action. Verbal protocol analyses confirmed that high scorers on SJTs without situation descriptions relied upon general rules about the effectiveness of the responses. Implications for SJT theory, research, and design are discussed

Candidate long-range regulatory sites acting on the IL17-pathway genes TRAF3IP2 and IL17RA are associated with psoriasis

Background: Drug-mediated disruption of IL17A, IL17F, and IL17RA proteins is effective in psoriasis. However, disruption of the IL17 pathway by functional mutations has so far only been shown to affect risk in IL23R and TRAF3IP2. It is unclear if this is due to rarity of disruptive mutations.Objective: (i) to delineate the prevalence of mutations in key IL17-pathway genes; (ii) to identify candidate regulatory sites acting on IL23R, IL17A, IL17RA, TRAF3IP2 from a distance.Methods: Extraction of mutation frequencies from ExAc data, evolutionary sequence alignment; mapping of long-range-interacting (LRI) enhancers; genetic association testing in a novel psoriasis cohort.Results: the prevalence of disruptive mutations in genes such as IL17RA is sufficient to have been detectable by existing datasets. Therefore, lack of their association with psoriasis indicates that genetic risk primarily resides in variants acting from a distance. We identify two LRI enhancer sites, regulating IL17RA and TRAF3IP2, respectively. The TRAF3IP2 regulator localises to the TRAF3IP2-antisense promoter, suggesting feedback-regulation. Both LRI sites are associated with psoriasis in a novel Scottish psoriasis cohort and the TRAF3IP2-LRI at rs71562294 replicates in the WTCCC cohort.Conclusion: Genetic risk for psoriasis may be encoded at LRI sites regulating IL17 pathway genes from a distance.</p

Association analysis identifies ZNF750 regulatory variants in psoriasis

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>ZNF750 </it>promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. <it>ZNF750 </it>encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene.</p> <p>Methods</p> <p>We examined whether <it>ZNF750 </it>variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of <it>ZNF750 </it>in 716 Caucasian psoriasis cases and 397 Caucasian controls.</p> <p>Results</p> <p>We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two <it>ZNF750 </it>haplotypes associated with psoriasis (p < 0.05). We also identified an excess of rare promoter and 5'untranslated region (UTR) variants in psoriasis cases compared to controls (p = 0.041), whereas there was no significant difference in the number of rare coding and rare 3' UTR variants. Using a promoter functional assay in stimulated human primary keratinocytes, we showed that four <it>ZNF750 </it>promoter and 5' UTR variants displayed a 35-55% reduction of <it>ZNF750 </it>promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a <it>ZNF750 </it>promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families.</p> <p>Conclusions</p> <p>Two haplotypes of <it>ZNF750 </it>and rare 5' regulatory variants of <it>ZNF750 </it>were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.</p

A Replication Study of the Association between Rheumatoid Arthritis and Deletion of the Late Cornified Envelope Genes LCE3B and LCE3C

OBJECTIVE: Two recent studies, in a Spanish and a Chinese population, point to an association between rheumatoid arthritis (RA) risk and the deletion of the Late Cornified Envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del), a known risk factor for psoriasis. We aimed to replicate these studies in a large Dutch cohort. METHODS: 1039 RA cases and 759 controls were genotyped for LCE3C_LCE3B-del. Association analysis was performed for the complete cohort and after stratification for the serologic markers anti-cyclic citrullinated peptide and rheumatoid factor. A meta-analysis was performed combining our data with the Spanish and Chinese datasets, resulting in an analysis including 2466 RA cases and 2438 controls. RESULTS: In the Dutch cohort we did not observe a significant association of LCE3C_LCE3B-del (p = 0.093) with RA risk. A stratified analysis for the serologic positive and negative group did not show an association between the genetic variant and disease risk, either. The meta-analysis, however, confirmed a significant association (p<0.0001, OR = 1.31, 95% confidence interval 1.16-1.47). CONCLUSION: Our meta-analysis confirms the association of the LCE3 deletion with RA, suggesting that LCE3C_LCE3B-del is a common risk factor for (auto)immune diseases

Susceptibility to type 1 diabetes conferred by the PTPN22 C1858T polymorphism in the Spanish population

<p>Abstract</p> <p>Background</p> <p>The protein tyrosine phosphatase N22 gene (<it>PTPN22</it>) encodes a lymphoid-specific phosphatase (LYP) which is an important downregulator of T cell activation. A <it>PTPN22 </it>polymorphism, C1858T, was found associated with type 1 diabetes (T1D) in different Caucasian populations. In this study, we aimed at confirming the role of this variant in T1D predisposition in the Spanish population.</p> <p>Methods</p> <p>A case-control was performed with 316 Spanish white T1D patients consecutively recruited and 554 healthy controls, all of them from the Madrid area. The <it>PTPN22 </it>C1858T SNP was genotyped in both patients and controls using a TaqMan Assay in a 7900 HT Fast Real-Time PCR System.</p> <p>Results</p> <p>We replicated for the first time in a Spanish population the association of the 1858T allele with an increased risk for developing T1D [carriers of allele T vs. CC: OR (95%) = 1.73 (1.17–2.54); p = 0.004]. Furthermore, this allele showed a significant association in female patients with diabetes onset before age 16 years [carriers of allele T vs. CC: OR (95%) = 2.95 (1.45–6.01), female patients vs female controls p = 0.0009]. No other association in specific subgroups stratified for gender, HLA susceptibility or age at onset were observed.</p> <p>Conclusion</p> <p>Our results provide evidence that the <it>PTPN22 </it>1858T allele is a T1D susceptibility factor also in the Spanish population and it might play a different role in susceptibility to T1D according to gender in early-onset T1D patients.</p

DNA Methylation and Gene Expression Changes in Monozygotic Twins Discordant for Psoriasis: Identification of Epigenetically Dysregulated Genes

Monozygotic (MZ) twins do not show complete concordance for many complex diseases; for example, discordance rates for autoimmune diseases are 20%–80%. MZ discordance indicates a role for epigenetic or environmental factors in disease. We used MZ twins discordant for psoriasis to search for genome-wide differences in DNA methylation and gene expression in CD4+ and CD8+ cells using Illumina's HumanMethylation27 and HT-12 expression assays, respectively. Analysis of these data revealed no differentially methylated or expressed genes between co-twins when analyzed separately, although we observed a substantial amount of small differences. However, combined analysis of DNA methylation and gene expression identified genes where differences in DNA methylation between unaffected and affected twins were correlated with differences in gene expression. Several of the top-ranked genes according to significance of the correlation in CD4+ cells are known to be associated with psoriasis. Further, gene ontology (GO) analysis revealed enrichment of biological processes associated with the immune response and clustering of genes in a biological pathway comprising cytokines and chemokines. These data suggest that DNA methylation is involved in an epigenetic dysregulation of biological pathways involved in the pathogenesis of psoriasis. This is the first study based on data from MZ twins discordant for psoriasis to detect epigenetic alterations that potentially contribute to development of the disease