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- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 2. |
- Savage, J. E., et al.
(författare)
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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:7, s. 912-919
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Tidskriftsartikel (refereegranskat)abstract
- Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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| 6. |
- Thompson, PM, et al.
(författare)
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ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
- 2020
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 100-
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Tidskriftsartikel (refereegranskat)abstract
- This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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| 7. |
- Grasby, Katrina L., et al.
(författare)
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Estimating Classroom-Level Influences on Literacy and Numeracy: A Twin Study
- 2020
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Ingår i: Journal of Educational Psychology. - : AMER PSYCHOLOGICAL ASSOC. - 0022-0663 .- 1939-2176. ; 112:6, s. 1154-1166
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Tidskriftsartikel (refereegranskat)abstract
- Classroom-level influences on literacy skills in kindergarten through Grade 2, and on literacy and numeracy skills in Grades 3. 5, 7, and 9. were examined by comparing the similarity of twins who shared or did not share classrooms with each other. We analyzed two samples using structural equation modeling adapted for twin data. The first, Study 1, was of Australia-wide tests of literacy and numeracy, with 1,098; 1,080; 790, and 812 complete twin pairs contributing data for Grades 3, 5, 7, and 9, respectively. The second, Study 2, was of literacy tests from 753 twin pairs from kindergarten through Grade 2, which included a sample of United States and Australian students and was a reanalysis and extension of Byrne et al. (2010). Classroom effects were mostly nonsignificant; they accounted for only 2-3% of variance in achievement when averaged over tests and grades. Although the averaged effects may represent a lower-bound figure for classroom effects, and the design cannot detect classroom influences limited to individual students, the results are at odds with claims in public discourse of substantial classroom-level influences, which are mostly portrayed as teacher effects.
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| 9. |
- von Haartman, M., et al.
(författare)
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Impact of strain and channel orientation on the low-frequency noise performance of Si n- and pMOSFETs
- 2007
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Ingår i: Solid-State Electronics. - : Elsevier BV. - 0038-1101 .- 1879-2405. ; 51:5, s. 771-777
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Tidskriftsartikel (refereegranskat)abstract
- Mobility and low-frequency (LF) noise were studied in tensile strained Si n- and pMOSFETs fabricated on relaxed SiGe virtual substrates. Both the impact of the channel orientation ((110) or (100) on (100) Si) and the tensile strain were carefully investigated. Two types of virtual substrates were used; a thin relaxed SiGe layer (20% Ge) and a thick one (27% Ge). The strained Si nMOSFETs fabricated on the thin substrate showed similar LF noise level as in the reference devices, whereas the thick substrate caused severely increased LF noise in the nMOSFETs. The latter was linked to the higher Ge concentration and explained by possible misfit dislocations and increased defect densities, likely resulting from strain relaxation caused by ion implantation damage. On the other hand, considerably lower LF noise was achieved in the pMOSFETs on the thick SiGe. The channel orientation was not found to have a significant influence on the LF noise performance in any of the studied devices.
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