| Title: |
Transcriptomic risk scores for attention deficit/hyperactivity disorder |
| Authors: |
Cabana-Domínguez, Judit; Llonga, Natalia; Arribas, Lorena; Alemany, Sílvia; Vilar-Ribó, L.; Demontis, Ditte; Fadeuilhe, Christian; Corrales, Montserrat; Richarte, Vanesa; Børglum, Anders D.; Ramos-Quiroga, Josep Antoni; Soler Artigas, María; Ribasés Haro, Marta; Universitat Autònoma de Barcelona |
| Publication Year: |
2023 |
| Collection: |
Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB |
| Subject Terms: |
Genetics; ADHD |
| Description: |
Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. We performed a transcriptome-wide association study (TWAS) using the latest genome-wide association study (GWAS) meta-analysis, in 38,691 individuals with ADHD and 186,843 controls, and 14 gene-expression reference panels across multiple brain tissues and whole blood. Based on TWAS results, we selected subsets of genes and constructed transcriptomic risk scores (TRSs) for the disorder in peripheral blood mononuclear cells of individuals with ADHD and controls. We found evidence of association between ADHD and TRSs constructed using expression profiles from multiple brain areas, with individuals with ADHD carrying a higher burden of TRSs than controls. TRSs were uncorrelated with the polygenic risk score (PRS) for ADHD and, in combination with PRS, improved significantly the proportion of variance explained over the PRS-only model. These results support the complementary predictive potential of genetic and transcriptomic profiles in blood and underscore the potential utility of gene expression for risk prediction and deeper insight in molecular mechanisms underlying ADHD. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
14765578 |
| Relation: |
Instituto de Salud Carlos III CP22/00026; Instituto de Salud Carlos III P19/01224; Instituto de Salud Carlos III PI20/00041; Instituto de Salud Carlos III PI22/00464; Instituto de Salud Carlos III FI18/00285; Instituto de Salud Carlos III CP22/00128; Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1461; Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00840; Ministerio de Ciencia, Innovación y Universidades JC2018-035346-I; European Commission 728018; European Commission 848228; European Commission 2020604; Fundació la Marató de TV3 202228-30; Fundació la Marató de TV3 202228-31; Molecular psychiatry; Vol. 28 (august 2023), p. 3493-3502; https://ddd.uab.cat/record/293467; urn:oai:ddd.uab.cat:293467; urn:pmcid:PMC10618083; urn:pmid:37537283; urn:oai:pubmedcentral.nih.gov:10618083; urn:articleid:14765578v28p3493 |
| Availability: |
https://ddd.uab.cat/record/293467 |
| Rights: |
open access ; Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.10268E9F |
| Database: |
BASE |