We have conducted a multicentre case-control study to assess the epidemiological importance of previously suggested risk factors for psoriasis, including family history of the disease, smoking and alcohol consumption. Newly diagnosed psoriatics, with a history of skin manifestations no longer than 2 years were eligible as cases; as controls we selected subjects with newly diagnosed dermatological conditions other than psoriasis. Interviews were performed by trained medical investigators using a structured questionnaire. Two-hundred and fifteen cases, aged 16-65 years (median age 38), and 267 controls, aged 15-65 years (median age 36), were interviewed and included in the analysis. Family history was a risk factor for psoriasis; the multiple logistic regression (MLR) adjusted-odds ratio was 18.8 (95% confidence interval 6.4-54.8) for a history in parents, and 3.2 (95% confidence interval 1.5-6.6) for a history in siblings. The risk of psoriasis was higher for current smokers than for those who had never smoked. The MLR adjusted odds ratio was 2.1 (95% confidence interval 1.1-4.0) for people smoking 15 cigarettes or more per day. The risk of psoriasis was higher for alcohol drinkers: compared with teetotallers the MLR adjusted-odds ratios were 1.3 (95% confidence interval 0.8-2.3) for subjects drinking one or two drinks/day and 1.6 (95% confidence interval 0.9 to 3.0) for those drinking three or more. However, the trend in risk was not statistically significant. Our study confirms the role of family history in psoriasis and provides some evidence of a dose-response relationship for an association between smoking habits and psoriasis.

Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Whole-genome sequencing of DNA samples from 71 Swedish patients with SLE and their healthy biological parents was performed to investigate the general genetic risk of SLE using known SLE GWAS risk loci identified using the ImmunoChip, variants in genes associated to monogenic SLE, and the mode of inheritance of SLE risk alleles in these families. A random forest model for predicting genetic risk for SLE showed that the SLE risk variants were mainly inherited from one of the parents. In the 71 patients, we detected a significant enrichment of ultra-rare ( ≤ 0.1%) missense and nonsense mutations in 22 genes known to cause monogenic forms of SLE. We identified one previously reported homozygous nonsense mutation in the C1QC (Complement C1q C Chain) gene, which explains the immunodeficiency and severe SLE phenotype of that patient. We also identified seven ultra-rare, coding heterozygous variants in five genes ( C1S, DNASE1L3, DNASE1, IFIH1 , and RNASEH2A ) involved in monogenic SLE. Our findings indicate a complex contribution to the overall genetic risk of SLE by rare variants in genes associated with monogenic forms of SLE. The rare variants were inherited from the other parent than the one who passed on the more common risk variants leading to an increased genetic burden for SLE in the child. Higher frequency SLE risk variants are mostly passed from one of the parents to the offspring affected with SLE. In contrast, the other parent, in seven cases, contributed heterozygous rare variants in genes associated with monogenic forms of SLE, suggesting a larger impact of rare variants in SLE than hitherto reported. Electronic supplementary material The online version of this article (10.1007/s00439-018-01966-7) contains supplementary material, which is available to authorized users.

Objective Complement components, including C4d, can be found on activated platelets, a process associated with vascular disease in SLE. We investigated whether platelet C4d (PC4d) adds additional value to traditional and known lupus-associated risk factors when identifying SLE patients with vascular disease. Methods This cross-sectional study included 308 well-characterized SLE patients and 308 matched general population controls. PC4d deposition was analysed using flow cytometry. Values >95% of controls were considered as PC4d positive (+). aPL were determined by Luminex, and the LA test was performed by DRVVT. History of vascular disease (composite and as separate outcomes) was defined at inclusion. Results SLE patients had increased PC4d deposition as compared with population controls (50 vs 5%, P < 0.0001). PC4d+ positively associated with any vascular events, and separately with venous and cerebrovascular events, and also with all investigated aPL profiles. The association for any vascular event remained statistically significant after adjustment for traditional and SLE-associated risk factors (odds ratio: 2.3, 95% CI: 1.3, 4.3, P = 0.008). Compared with patients negative for both PC4d and LA, patients with double positivity were more likely to have vascular disease (odds ratio: 12.3, 95% CI: 5.4, 29.3; attributable proportion due to interaction 0.8, 95% CI: 0.4, 1.1) Conclusion PC4d+ is associated with vascular events in SLE, independently of traditional and SLE-associated risk factors. Concurrent presence of PC4d and LA seem to interact to further increase the odds for vascular events. Prospective studies should examine whether the aPL/PC4d combination can improve prediction of vascular events in SLE and/or APS.