Genetic study of psoriasis highlights its close link with socio-economic status and affective symptoms

Psoriasis is an inflammatory skin disease with an estimated heritability of around 70 %. Previous genome-wide association studies (GWASs) have detected several risk loci for psoriasis. To further improve the understanding of the genetic risk factors impacting the disease, we conducted a discovery GWAS in FinnGen and a subsequent replication and meta-analysis with data from the Estonian Biobank and the UK biobank; the study sample included 925 649 individuals (22 659 cases and 902 990 controls), the largest sample for psoriasis yet. In addition, we conducted downstream analyses to find out more about psoriasis’ cross-trait genetic correlations and causal relationships. We report 8 novel risk loci, most of which harbor genes related to nuclear factor kappa-light-chain-enhancer of activated B-cells-signaling pathway and overall immunity. Genetic correlations highlight the relationship between psoriasis and smoking, higher body weight, and lower education level. Additionally, we report novel causal relationships between psoriasis and mood symptoms, as well as two-directioned causal relationship between psoriasis and lower education level. Our results provide new knowledge on psoriasis risk factors, which may be useful in the development of future treatment strategies. ### Competing Interest Statement Dr. Huilaja has received educational grants from Takeda, Janssen-Cilag, Novartis, AbbVie and LEO Pharma, honoraria from Lilly, Sanofi, Novartis, Abbvie, LeoPharma, Boehringel Ingelheim and OrionPharma for consulting and/or speaking, and is an investigator for Abbvie, Takeda and Amgen. KT has received educational grants from Novartis and honoraria from Abbvie, Leo Pharma, Novartis, Sanofi Genzyme, Janssen-Cilag, Bristol-Myers Squibb and UCB Pharma for consulting and/or speaking. ### Funding Statement ES was funded by Academy of Finland (338229) and Orion Research Foundation. JK was funded by Sigrid Juselius foundation. Estonian Biobank research was supported by Estonian Research Council grant PRG1291. The FinnGen project is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie Inc., AstraZeneca UK Ltd, Biogen MA Inc., Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sàrl), Genentech Inc., Merck Sharp & Dohme LCC, Pfizer Inc., GlaxoSmithKline Intellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Janssen Biotech Inc, Novartis AG, and Boehringer Ingelheim International GmbH. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The FinnGen study is approved by Finnish Institute for Health and Welfare (permit numbers: THL/2031/6.02.00/2017, THL/1101/5.05.00/2017, THL/341/6.02.00/2018, THL/2222/6.02.00/2018, THL/283/6.02.00/2019, THL/1721/5.05.00/2019, THL/1524/5.05.00/2020, and THL/2364/14.02/2020), Digital and population data service agency (permit numbers: VRK43431/2017-3, VRK/6909/2018-3, VRK/4415/2019-3), the Social Insurance Institution (permit numbers: KELA 58/522/2017, KELA 131/522/2018, KELA 70/522/2019, KELA 98/522/2019, KELA 138/522/2019, KELA 2/522/2020, KELA 16/522/2020, Findata THL/2364/14.02/2020 and Statistics Finland (permit numbers: TK-53-1041-17 and TK/143/07.03.00/2020 (earlier TK-53-90-20). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Summary statistics will be made available through the NHGRI-EBI GWAS Catalog with GCSTxxxxxxx upon publication. The Finnish biobank data can be accessed through the Fingenious® services () managed by FINBB.