Exploring genetic variants in obsessive compulsive disorder severity: A GWAS approach.

BACKGROUND: The severity of Obsessive-Compulsive Disorder (OCD) varies significantly among probands. No study has specifically investigated the genetic base of OCD severity. A previous study from our group found an OCD polygenic risk score to predict pre- and post-treatment severity. This study expl...

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Detalles Bibliográficos
Autores: Alemany-Navarro M, Cruz R, Real E, Segalàs C, Bertolín S, Baenas I, Domènech L, Rabionet R, Carracedo Á, Menchón JM, Alonso P
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p17418
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17418
Access Level:acceso abierto
Palabra clave:Common variants
GWAS
Genomics
Obsessive-compulsive disorder
Rare variants
Severity
Descripción
Sumario:BACKGROUND: The severity of Obsessive-Compulsive Disorder (OCD) varies significantly among probands. No study has specifically investigated the genetic base of OCD severity. A previous study from our group found an OCD polygenic risk score to predict pre- and post-treatment severity. This study explores the genomic bases of OCD severity. METHODS: We administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to 401 patients at their first visit to our clinic to measure their OCD severity. Genotyping data was collected by using the Infinium PsychArray-24 BeadChip kit (Illumina). We analyzed genetic association with OCD severity in a linear regression analysis at single-nucleotide polymorphism (SNP)- and gene-levels, this last also considering rare variants. Enrichment analyses were performed from gene-based analyses' results. RESULTS: No SNP reached significant association (p < 10(-8)) with the YBOCS. Six markers showed suggestive association (p < 10(-5)). The top SNP was an intergenic variant in chromosome 2: rs7578149 (p < 1.89 × 10(-6)), located in a region suggestively associated with MDD. Linkage disequilibrium was found for two clusters of SNPs located between SLC16A14 and SP110 in chromosome 2, all of them forming one peak of association. Enrichment analyses revealed OCD genes to be associated with porin activity (FDR = 0.01) and transmembrane structure (FDR = 0.04). LIMITATIONS: The size of the sample and the transversal nature of the severity measure are limitations of this study. CONCLUSION: This study contributes to better characterize OCD at an individual level, helping to know more about the prognosis of the disorder and develop more individualized treatments.