Exploring genetic variants in obsessive compulsive disorder severity: A GWAS approach.
Por:
Alemany-Navarro M, Cruz R, Real E, Segalàs C, Bertolín S, Baenas I, Domènech L, Rabionet-Janssen R, Carracedo Á, Menchón JM and Alonso P
Publicada:
15 abr 2020
Ahead of Print:
29 ene 2020
Resumen:
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.
Filiaciones:
Alemany-Navarro M:
Institut d' Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
Cruz R:
Grupo de Medicina Xenómica, CIBERER, Centre for Research in Molecular Medicine and Chronic Diseases, CIMUS-, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Real E:
Institut d' Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
Segalàs C:
Institut d' Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
Bertolín S:
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
Baenas I:
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
Domènech L:
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain
Universitat Pompeu Fabra (UPF), Barcelona, Spain
Rabionet-Janssen R:
Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain
Institut de Biomedicina de la Universitat de Barcelona (IBUB), CIBERER, and Dept. Genetics, Microbiology & statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain
Carracedo Á:
Grupo de Medicina Xenómica, CIBERER, Centre for Research in Molecular Medicine and Chronic Diseases, CIMUS-, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Fundación Pública Galega de Medicina Xenómica, SERGAS, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain
Menchón JM:
Institut d' Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain
CIBERSAM (Centro de Investigación en Red de Salud Mental), Instituto de Salud Carlos III, Spain
Alonso P:
OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain
Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain
CIBERSAM (Centro de Investigación en Red de Salud Mental), Instituto de Salud Carlos III, Spain
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