Genome-wide pathway analysis identifies genetic pathways associated with psoriasis

Aterido Ballonga, Adrià, 1990-; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; Cueva, Pablo de la; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume, 1952-; Absher, Devin; Capon, Francesca; Myers, Richard M.; Barker, Jonathan N.; Marsal, Sara

Genome-wide pathway analysis identifies genetic pathways associated with psoriasis

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dc.contributor.author Aterido Ballonga, Adrià, 1990-ca
dc.contributor.author Julià, Antonioca
dc.contributor.author Ferrándiz, Carlosca
dc.contributor.author Puig, Lluísca
dc.contributor.author Fonseca, Eduardoca
dc.contributor.author Fernández-López, Emiliaca
dc.contributor.author Dauden, Estebanca
dc.contributor.author Sánchez-Carazo, José Luísca
dc.contributor.author López-Estebaranz, José Luísca
dc.contributor.author Moreno-Ramírez, Davidca
dc.contributor.author Vanaclocha, Franciscoca
dc.contributor.author Herrera, Enriqueca
dc.contributor.author Cueva, Pablo de laca
dc.contributor.author Dand, Nickca
dc.contributor.author Palau, Núriaca
dc.contributor.author Alonso, Arnaldca
dc.contributor.author López-Lasanta, Maríaca
dc.contributor.author Tortosa, Raülca
dc.contributor.author García-Montero, Andrésca
dc.contributor.author Codó, Laiaca
dc.contributor.author Gelpí, Josep Lluísca
dc.contributor.author Bertranpetit, Jaume, 1952-ca
dc.contributor.author Absher, Devinca
dc.contributor.author Capon, Francescaca
dc.contributor.author Myers, Richard M.ca
dc.contributor.author Barker, Jonathan N.ca
dc.contributor.author Marsal, Saraca
dc.date.accessioned 2018-03-14T10:17:34Z
dc.date.available 2018-03-14T10:17:34Z
dc.date.issued 2016
dc.description.abstract Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P < 0.05). These findings provide insights into the biological mechanisms associated with psoriasis susceptibility.
dc.description.sponsorship This study was funded by of the Spanish Ministry of Economy and Competitiveness, grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36
dc.format.mimetype application/pdf
dc.identifier.citation Aterido A, Julià A, Ferrándiz C, Puig L, Fonseca E, Fernández-López E et al. Genome-wide pathway analysis identifies genetic pathways associated with psoriasis. J Invest Dermatol. 2016 Mar;136(3):593-602. DOI: 10.1016/j.jid.2015.11.026
dc.identifier.doi http://dx.doi.org/10.1016/j.jid.2015.11.026
dc.identifier.issn 0022-202X
dc.identifier.uri http://hdl.handle.net/10230/34099
dc.language.iso eng
dc.publisher Elsevierca
dc.relation.ispartof Journal of Investigative Dermatology. 2016 Mar;136(3):593-602
dc.rights © Elsevier. This is the published version of an article http://dx.doi.org/10.1016/j.jid.2015.11.026 that appeared in the Journal of investigative dermatology. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Psoriasi
dc.subject.other Genòmica
dc.subject.other Genètica
dc.title Genome-wide pathway analysis identifies genetic pathways associated with psoriasisca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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