Meta-analysis of Genome wide Association Studies on Childhood ADHD Symptoms and Diagnosis Reveals 17 Novel Loci and 22 Potential Effector Genes
Van der Laan, C. M.; Ip, H. F.; Schipper, M.; Hottenga, J.-J.; Krapohl, E. M.; Brikell, I.; Soler Artigas, M.; Cabana-Dominguez, J.; Llonga, N.; Nolte, I. M.; St Pourcain, B.; Bolhuis, K.; Palviainen, T.; Zafarmand, H.; Gordon, S.; Zayats, T.; Aliev, F.; Burt, A. S.; Wang, C. A.; Saunders, G.; Karhunen, V.; Adkins, D. E.; Border, R.; Peterson, R. E.; Prinz, J. A.; Thiering, E.; Vilor-Tejedor, N.; Ahluwalia, T. S.; Allegrini, A.; Rimfeld, K.; Chen, Q.; Lu, Y.; Martin, J.; Bosch, R.; Ramos Quiroga, J. A.; Neumann, A.; Ensink, J.; Grasby, K.; Morosoli, J. J.; Tong, X.; Marrington, S.; Scott, J. G
Show abstract
Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder for which genetic factors explain up to 75% of the variance. In this study, we performed a genome-wide association meta-analysis (GWAMA) of ADHD symptom measures, with an effective sample size of 120,092 (71,733 unique individuals from 28 population-based cohorts, with 288,887 quantitative ADHD symptom measures). Next, we meta-analyzed the results with a genome-wide association study (GWAS) of ADHD diagnosis. The GWAMA of ADHD symptoms returned no genome-wide significant variants. However, we estimated strong genetic correlations between our study of quantitative ADHD symptoms and the earlier study of ADHD diagnosis (rg= 1.00, SE= 0.06). Moderate negative genetic correlations (rg< -0.40) were observed with several cognitive traits. Genetic correlations between ADHD and aggressive behavior and antisocial behavior were around 1. This provides further evidence of the wide pleiotropic effects of genetic variants and the role that genetic variants play in the co-occurrence with (mental) health traits. The GWAMAs of ADHD symptoms and diagnosis identified 2,039 genome-wide significant variants, representing 39 independent loci, of which 17 were new. Using a novel fine-mapping and functional annotation method, we identified 22 potential effector genes which implicate several new potential biological processes and pathways that may play a role in ADHD. Our findings support the notion that clinical ADHD is at the extreme end of a continuous liability that is indexed by ADHD symptoms. We show that including ADHD symptom counts in large-scale GWAS can be useful to identify novel genes implicated in ADHD and related symptoms.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention deficit hyperactivity disorder 95%
- Polygenic profiles define aspects of clinical heterogeneity in ADHD 95%
- Identification of shared and differentiating genetic risk for autism spectrum disorder, attention deficit hyperactivity disorder and case subgroups 94%
Similar papers in this journal
- Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder 96%
- TWAS pathway method greatly enhances the number of leads for uncovering the molecular underpinnings of psychiatric disorders 94%
- Sites of active gene regulation in the prenatal frontal cortex and their role in neuropsychiatric disorders 94%
Similar papers in this journal
- Using DNA to predict behaviour problems from preschool to adulthood 94%
- Combined polygenic risk scores of different psychiatric traits predict general and specific psychopathology in childhood 93%
- Analysis of structural brain asymmetries in Attention-Deficit/Hyperactivity Disorder in 39 datasets 92%
Similar papers in this journal
- Integrating HiTOP and RDoC Frameworks Part II: Shared and Distinct Biological Mechanisms of Externalizing and Internalizing Psychopathology 95%
- Evidence of shared genetic influences underlying schizophrenia and alcohol use disorder, but not alcohol consumption 94%
- A Multivariate Genome-Wide Association Study Reveals Neural Correlates and Common Biological Mechanisms of Psychopathology Spectra 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.