Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high heritability. At least 30% of patients diagnosed in childhood continue to suffer from ADHD during adulthood and genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. To date, genome-wide association studies (GWAS) of ADHD have been completed in seven independent datasets, six of which were pediatric samples and one on persistent ADHD using a DNA-pooling strategy, but none of them reported genome-wide significant associations. In an attempt to unravel novel genes for the persistence of ADHD into adulthood, we conducted the first two-stage GWAS in adults with ADHD. The discovery sample included 607 ADHD cases and 584 controls. Top signals were subsequently tested for replication in three independent follow-up samples of 2104 ADHD patients and 1901 controls. None of the findings exceeded the genome-wide threshold for significance (PGC<5e-08), but we found evidence for the involvement of the FBXO33 (F-box only protein 33) gene in combined ADHD in the discovery sample (P=9.02e-07) and in the joint analysis of both stages (P=9.7e-03). Additional evidence for a FBXO33 role in ADHD was found through gene-wise and pathway enrichment analyses in our genomic study. Risk alleles were associated with lower FBXO33 expression in lymphoblastoid cell lines and with reduced frontal gray matter volume in a sample of 1300 adult subjects. Our findings point for the first time at the ubiquitination machinery as a new disease mechanism for adult ADHD and establish a rationale for searching for additional risk variants in ubiquitination-related genes.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330505PMC
http://dx.doi.org/10.1038/npp.2014.267DOI Listing

Publication Analysis

Top Keywords

genome-wide association
8
attention-deficit hyperactivity
8
hyperactivity disorder
8
adhd
8
adhd adulthood
8
disorder
5
case-control genome-wide
4
association study
4
study persistent
4
persistent attention-deficit
4

Similar Publications

Background: Glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used in manageing type 2 diabetes mellitus and weight control. Their potential in treating ageing-related diseases has been gaining attention in recent years. However, the long-term effects of GLP1RAs on these diseases have yet to be fully revealed.

View Article and Find Full Text PDF

Background: Antibiotics have recently been suggested to increase the risk of colorectal cancer. Here, we aimed to investigate the association of frequent antibiotic use and genetic susceptibility with the increased risk of the development of colorectal cancer. Therefore, a genome-wide association study was conducted in colorectal cancer patients with frequent antibiotic use and controls to identify potential chromosomal regions that could indicate an increased risk of colorectal cancer associated with antibiotic use.

View Article and Find Full Text PDF

Circulating glycine levels have been associated with reduced risk of coronary artery disease (CAD) in humans but these associations have not been observed in all studies. We evaluated whether the relationship between glycine levels and atherosclerosis was causal using genetic analyses in humans and feeding studies in mice. Serum glycine levels were evaluated for association with risk of CAD in the UK Biobank.

View Article and Find Full Text PDF

Genome-Wide Identification and Functional Characterization of Gene Family Reveal Its Involvement in Response to Stress in Cotton.

Int J Mol Sci

January 2025

Institute of Cotton, Hebei Academy of Agriculture and Forestry Sciences/Key Laboratory of Cotton Biology and Genetic Breeding in Huanghuaihai Semiarid Area, Ministry of Agriculture and Rural Affairs, Shijiazhuang 050000, China.

SKP1 constitutes the Skp1-Cullin-F-box ubiquitin E3 ligase (SCF), which plays a role in plant growth and development and biotic and abiotic stress in ubiquitination. However, the response of the gene family to abiotic and biotic stresses in cotton has not been well characterized. In this study, a total of 72 genes with the conserved domain of SKP1 were identified in four Gossypium species.

View Article and Find Full Text PDF

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by widespread inflammation and autoantibody production. Its development and progression involve genetic, epigenetic, and environmental factors. Although genome-wide association studies (GWAS) have repeatedly identified a susceptibility signal at 16p13, its fine-scale source and its functional and mechanistic role in SLE remain unclear.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!