Recent genome-wide association studies (GWASs) have identified >20 new loci associated with the susceptibility to psoriasis vulgaris (PsV) risk. We investigated the association of PsV and its main clinical subphenotypes with 32 loci having previous genome-wide evidence of association with PsV (P < 5e-8) or strong GWAS evidence (P < 5e-5 in discovery and P < 0.05 in replication sample) in a large cohort of PsV patients (n = 2005) and controls (n = 1497). We provide the first independent replication for COG6 (P = 0.00079) and SERPINB8 (P = 0.048) loci with PsV. In those patients having developed psoriatic arthritis (n = 955), we found, for the first time, a strong association with IFIH1 (P = 0.013). Analyses of clinically relevant PsV subtypes yielded a significant association of severity of cutaneous disease with variation at LCE3D locus (P = 0.0005) in PsV and nail involvement with IL1RN in purely cutaneous psoriasis (PsC, P = 0.007). In an exploratory analysis of epistasis, we replicated the previously described HLA-C-ERAP1 interaction with PsC. Our findings show that common genetic variants associated with a complex phenotype like PsV influence different subphenotypes of high clinical relevance.

ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.MethodsWe performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case–control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.ResultsWe identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs.ConclusionThese findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

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RESUMENFundamento: El fenómeno conocido como consumo concentrado de alcohol y otras drogas se produce de manera frecuente entre los jóvenes en las áreas recreativas nocturnas. El presente estudio analiza las conductas de riesgo y la siniestralidad asociada al alcohol y otras drogas en una muestra de jóvenes que participan de la vida recreativa nocturna.Método: Participaron 440 jóvenes de 3 comunidades autóno-mas. El tamaño de la muestra fue estimado mediante Respondent Driven Sampling. Los análisis estadísticos exploraron frecuencias y medidas de asociación de conductas de riesgo en conducción en relación con la siniestralidad, número de estados de embriaguez, frecuencia de accidentes en el último mes, influencia de sexo y edad, así como la potencia predictiva de dichas variables respecto a la siniestralidad.Resultados: Un 50,2% de los jóvenes ha subido con un conductor ebrio y/o drogado, un 23,2% ha conducido embriagado y un 23,5% bajos los efectos de otras drogas. A mayor implicación en la noche, mayor frecuencia de embriaguez [chi 2 (9)=112,24; p<,000]; a mayor número de borracheras, mayor frecuencia en las conductas: subirse con otros conductores ebrios o drogados [chi 2 = 36.442, (3) p<0.001], conducir ebrio [chi 2 =23,748, (3) p<0,001] y conducir drogado [chi 2 = 23,816 (3) p<0,001]. El análisis de regresión destacó conducir ebrio (odds-ratio=5,4) como conducta de riesgo más asociada a los accidentes de tráfico.Conclusiones: Las conductas de riesgo durante la conducción de vehículos muestran una elevada incidencia. Embriaguez, uso de drogas e implicación en la noche aumentan la frecuencia de dichas conductas. Conducir ebrio fue el mejor predictor de los accidentes.Palabras clave: Trafico, accidente. Prevención, accidente. Jóve-nes. Alcohol. Drogas ilegales. ABSTRACT Relationship between Alcohol, Drug Use and Traffic Accidents Related to Nightlife among a Spanish Youth Sample in Three Autonomous Communities in 2007Background: The phenomenon known as binge drinking and other drug abuse frequently occurs among young people in nightliferelated areas. This study analyzes the risk behaviours and the accident rate related to alcohol and other drugs among a sample of young people involved in nightlife.Method: A total of 440 young people from 3 Spanish Autonomous Communities took part. The sample size was estimated by means of Respondent Driven Sampling. The statistical analyses mined frequencies and measurements of the relationship of driving risk-related behaviour in relation to the accident rate, number of cases of drunkenness, frequency of accidents during the past month, influence of gender and age, as well as the predictiveness of these variables as regards the accident rate.Results: A total of 50.2% of these young people had gotten into a vehicle with a driver who was drunk and/or under the influence of drugs, 23.2% has driven when drunk and 23.5% under the influence of drugs. The greater the degree of involvement in nightlife, the higher the frequency of drunkenness [chi 2 (9)=112.24; p<.000]; the greater t...