| 1. |
- Demontis, D, et al.
(författare)
-
Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 576-
-
Tidskriftsartikel (refereegranskat)abstract
- Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Rajagopal, VM, et al.
(författare)
-
Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity
- 2023
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 429-
-
Tidskriftsartikel (refereegranskat)abstract
- Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots.
|
|
| 6. |
|
|
| 7. |
- Zhang, W, et al.
(författare)
-
Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3834-
-
Tidskriftsartikel (refereegranskat)abstract
- Transcriptome-wide association studies integrate gene expression data with common risk variation to identify gene-trait associations. By incorporating epigenome data to estimate the functional importance of genetic variation on gene expression, we generate a small but significant improvement in the accuracy of transcriptome prediction and increase the power to detect significant expression-trait associations. Joint analysis of 14 large-scale transcriptome datasets and 58 traits identify 13,724 significant expression-trait associations that converge on biological processes and relevant phenotypes in human and mouse phenotype databases. We perform drug repurposing analysis and identify compounds that mimic, or reverse, trait-specific changes. We identify genes that exhibit agonistic pleiotropy for genetically correlated traits that converge on shared biological pathways and elucidate distinct processes in disease etiopathogenesis. Overall, this comprehensive analysis provides insight into the specificity and convergence of gene expression on susceptibility to complex traits.
|
|
