Transcriptome-wide association study of attention deficit hyperactivity disorder identifies associated genes and phenotypes
| Autor: | Alexandre D. Laporte, Fulya Akçimen, Ridha Joober, Guy A. Rouleau, Dan Spiegelman, Calwing Liao, Patrick A. Dion |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Dopamine Agents Gene Expression General Physics and Astronomy Genome-wide association study Transcriptome Norepinephrine 0302 clinical medicine p300-CBP Transcription Factors lcsh:Science Genetics 0303 health sciences Multidisciplinary Genomics Amygdala Phenotype medicine.anatomical_structure Schizophrenia Behavioural genetics Genotype Fatty Acid Elongases Science Nerve Tissue Proteins Biology Polymorphism Single Nucleotide behavioral disciplines and activities Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences mental disorders medicine ADHD Humans Attention deficit hyperactivity disorder Genetic Predisposition to Disease Genetic association study Probability 030304 developmental biology Genetic association Membrane Proteins General Chemistry medicine.disease 030227 psychiatry Dorsolateral prefrontal cortex 030104 developmental biology Attention Deficit Disorder with Hyperactivity Genetic Loci lcsh:Q 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-7 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental psychiatric disorder. Genome-wide association studies (GWAS) have identified several loci associated with ADHD. However, understanding the biological relevance of these genetic loci has proven to be difficult. Here, we conduct an ADHD transcriptome-wide association study (TWAS) consisting of 19,099 cases and 34,194 controls and identify 9 transcriptome-wide significant hits, of which 6 genes were not implicated in the original GWAS. We demonstrate that two of the previous GWAS hits can be largely explained by expression regulation. Probabilistic causal fine-mapping of TWAS signals prioritizes KAT2B with a posterior probability of 0.467 in the dorsolateral prefrontal cortex and TMEM161B with a posterior probability of 0.838 in the amygdala. Furthermore, pathway enrichment identifies dopaminergic and norepinephrine pathways, which are highly relevant for ADHD. Overall, our findings highlight the power of TWAS to identify and prioritize putatively causal genes. A recent GWAS reported 12 genetic loci for attention deficit/hyperactivity disorder (ADHD). Here, Liao et al. perform transcriptomic imputation using these data and 12 brain-relevant tissues from GTEx and CMC to identify 9 genes associated with ADHD by TWAS, 3 of which had not yet been reported for ADHD. |
| Databáze: | OpenAIRE |
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