Summary To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of three genome-wide association studies (GWAS) and two independent datasets genotyped on the Immunochip, involving 10,588 cases and 22,806 controls in total. We identified 15 new disease susceptibility regions, increasing the number of psoriasis-associated loci to 36 for Caucasians. Conditional analyses identified five independent signals within previously known loci. The newly identified shared disease regions encompassed a number of genes whose products regulate T-cell function (e.g. RUNX3, TAGAP and STAT3). The new psoriasis-specific regions were notable for candidate genes whose products are involved in innate host defense, encoding proteins with roles in interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C), and NF-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

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BackgroundIn studies in Gothenburg, Sweden, in the 1990s of an aluminium hydroxide-adsorbed pertussis toxoid vaccine, 745 of ∼76 000 vaccinated children developed long-lasting itchy subcutaneous nodules at the vaccination site. Of 495 children with itchy nodules patch tested for aluminium allergy, 376 (76%) were positive.ObjectivesTo study the prognosis of the vaccine-induced aluminium allergy.Patients and methodsTwo hundred and forty-one children with demonstrated aluminium allergy in the previous study were patch tested again 5–9 years after the initial test, with the same procedure as used previously.ResultsContact allergy to aluminium was no longer demonstrable in 186 of the retested 241 children (77%). A negative test result was more common in children who no longer had itching at the vaccination site; it was also related to the age of the child, the time after the first aluminium-adsorbed vaccine dose, and the strength of the reaction in the first test.ConclusionsPatch test reactivity to aluminium seems to disappear or weaken with time.

We present epidemiological data for 5197 families with psoriasis. Errors in reporting have been analysed. Analysis of the data provides indications of random mating with respect to whether the partner has the skin disease or not. Data on psoriasis among parents, siblings and children are provided, and particular attention has been paid to the age at onset of psoriasis. Psoriasis was present in the parents of about 36% of the probands. In families in which one or both parents have psoriasis, the occurrence of the disease among the siblings does not provide any information which differentiates between a dominant and recessive mode of inheritance, but is compatible with both. In families in which neither parent had psoriasis, provided there was a proband with psoriasis, the probability of the siblings suffering from psoriasis was close to 0.25, indicating a recessive mode of inheritance. The distribution of psoriasis among the parents of all probands, and among the children of probands, was also compatible with this mode of inheritance. The prevalence of psoriasis in the elderly was estimated to be about 5%, and the gene frequency in the whole population 25%. These findings show that, with regard to first-degree relatives, the inheritance of psoriasis can fit an autosomal recessive model. The concept of a recessive mode of inheritance may be used as a basis for genetic counselling.

The age at onset of psoriasis has been analysed for 11.3fS6 psoriasis patients. The age at onset for siblings of probands has been analysed for 805 probands having one affected sibling and for 1 79 probands having two affected siblings. The age at onset curve for all probands shows a dominating maximum at about puberty but also indications for two more maxima at about 30 and 50 years of age. respectively. A more relevant picture ofthe risk of getting psoriasis at different ages is obtained if the onset for old people having psoriasis is investigated. The three maxima come out more clearly in this case, and the puberty maximum is not so dominating. For the families with one proband and two affected siblings there is a statistically signiiicant correlation (P<0-001) between the age at onset of the proband and ofthe siblings, and also between the siblings. The correlation coefficient is between 0-30 and 0-45. For the probands with one affected sibling, the ages at onset of the siblings mainly fall in the same range as those ofthe probands. These dnin indicate three groups of patients with respect to age at onset. However, the overlap between the different groups is considerable. The data presented are compatible with three, possibly genetically different, variants of psoriasis vulgaris. By studying the occurrence of psoriasis among parents of the probands. the gene frequency can be estimated assuming a recessive mode of inheritance. It then turns out that the gene frequency ofthe group with the earliest age at onset has a gene frequency of about 0-25. the next earliest. 0-18. and the latest, 0-14.