RT Journal Article
T1 Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.
A1 Aterido, Adrià
A1 Julià, Antonio
A1 Ferrándiz, Carlos
A1 Puig, Lluís
A1 Fonseca, Eduardo
A1 Fernández-López, Emilia
A1 Dauden, Esteban
A1 Sánchez-Carazo, José Luís
A1 López-Estebaranz, José Luís
A1 Moreno-Ramírez, David
A1 Vanaclocha, Francisco
A1 Herrera, Enrique
A1 de la Cueva, Pablo
A1 Dand, Nick
A1 Palau, Núria
A1 Alonso, Arnald
A1 López-Lasanta, María
A1 Tortosa, Raül
A1 García-Montero, Andrés
A1 Codó, Laia
A1 Gelpí, Josep Lluís
A1 Bertranpetit, Jaume
A1 Absher, Devin
A1 Capon, Francesca
A1 Myers, Richard M
A1 Barker, Jonathan N
A1 Marsal, Sara
AB 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
YR 2015
FD 2015-12-29
LK http://hdl.handle.net/10668/9712
UL http://hdl.handle.net/10668/9712
LA en
DS RISalud
RD Apr 8, 2025