Polygenic risk for psychiatric disorders correlates with executive function in typical development.

Published on Apr 1, 2019in Genes, Brain and Behavior3.397
· DOI :10.1111/GBB.12480
Andrew J. Schork35
Estimated H-index: 35
(UCSD: University of California, San Diego),
Timothy T. Brown34
Estimated H-index: 34
(UCSD: University of California, San Diego)
+ 5 AuthorsNatacha Akshoomoff46
Estimated H-index: 46
(UCSD: University of California, San Diego)
Author(s): Schork, A J; Brown, T T; Hagler, D J; Thompson, W K; Chen, C-H; Dale, A M; Jernigan, T L; Akshoomoff, N | Abstract: Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive functions and how these factors may be related to those that predispose to psychiatric disorders. We examined the relationship between polygenic risk scores built from large genome-wide association studies of psychiatric disorders and executive functioning in typically developing children. In our discovery sample (N = 417), consistent with previous reports on general cognitive abilities, polygenic risk for autism spectrum disorder was associated with better performance on the Dimensional Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in the youngest children. Polygenic risk for major depressive disorder was associated with poorer performance on the Flanker test in the same sample. This second association replicated for performance on the Penn Conditional Exclusion Test in an independent cohort (N = 3681). Our results suggest that the molecular genetic factors contributing to variability in executive function during typical development are at least partially overlapping with those associated with psychiatric disorders, although larger studies and further replication are needed.
📖 Papers frequently viewed together
12 Citations
9 Authors (Rachel L. Kember, ..., Maja Bucan)
#1Ebba Du Rietz ('KCL': King's College London)H-Index: 9
#2Jonathan R.I. Coleman ('KCL': King's College London)H-Index: 28
Last. Jonna Kuntsi ('KCL': King's College London)H-Index: 63
view all 6 authors...
Abstract Background A recent large-scale mega genome-wide association study identified, for the first time, genetic variants at 12 loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). In this study we use a powerful polygenic approach, with polygenic scores derived from the genome-wide association study, to investigate the etiological overlap between ADHD and frequently co-occurring traits and disorders. Methods Polygenic risk scores for ADHD derived from the mega ...
45 CitationsSource
#1Sumit Mistry (UoB: University of Bristol)H-Index: 4
#2Judith R. Harrison (Cardiff University)H-Index: 5
Last. Stanley ZammitH-Index: 73
view all 5 authors...
Abstract Studying the phenotypic manifestations of increased genetic liability for schizophrenia can increase our understanding of this disorder. Specifically, information from alleles identified in genome-wide association studies can be collapsed into a polygenic risk score (PRS) to explore how genetic risk is manifest within different samples. In this systematic review, we provide a comprehensive assessment of studies examining associations between schizophrenia PRS (SZ-PRS) and several phenot...
63 CitationsSource
#1Suzanne Sniekers (VU: VU University Amsterdam)H-Index: 4
#2Sven Stringer (VU: VU University Amsterdam)H-Index: 20
Last. Danielle Posthuma (VU: VU University Amsterdam)H-Index: 101
view all 30 authors...
Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta- A nalysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. G...
297 CitationsSource
#1Chelsie E. Benca (CU: University of Colorado Boulder)H-Index: 2
#2Jaime Derringer (UIUC: University of Illinois at Urbana–Champaign)H-Index: 27
Last. Naomi P. Friedman (CU: University of Colorado Boulder)H-Index: 28
view all 7 authors...
Executive functions (EFs) have been proposed as an endophenotype for psychopathology because EF deficits are associated with most psychiatric disorders. To examine this hypothesis, we derived polygenic risk scores for autism, attention-deficit/hyperactive disorder (ADHD), bipolar disorder, major depression (MDD), and schizophrenia, using genome-wide data from the Psychiatric Genomics Consortium as discovery samples. We then examined the relationships between these polygenic risk scores and three...
12 CitationsSource
#1Lucy Riglin (Cardiff University)H-Index: 17
#2Stephan Collishaw (Cardiff University)H-Index: 36
Last. Anita Thapar (Cardiff University)H-Index: 91
view all 7 authors...
Summary Background Schizophrenia typically onsets after puberty but is often preceded by observable childhood neurodevelopmental impairments. Whether these childhood antecedents index genetic liability is unknown. We used polygenic risk scores derived from a patient discovery sample as indicators of the genetic liability of schizophrenia. Our aim was to identify the early childhood manifestations of this liability in a UK population-based cohort. Methods The study sample was the Avon Longitudina...
88 CitationsSource
#1Laura GermineH-Index: 23
#2Elise B. Robinson (Broad Institute)H-Index: 38
Last. Raquel E. Gur (UPenn: University of Pennsylvania)H-Index: 142
view all 12 authors...
Association between polygenic risk for schizophrenia, neurocognition and social cognition across development
43 CitationsSource
#1Evie Stergiakouli (UoB: University of Bristol)H-Index: 18
#2Joanna Martin (Cardiff University)H-Index: 28
Last. George Davey Smith (UoB: University of Bristol)H-Index: 250
view all 8 authors...
Background: Children with a diagnosis of attention-deficit hyperactivity disorder (ADHD) have lower cognitive ability and are at risk of adverse educational outcomes; ADHD genetic risks have been found to predict childhood cognitive ability and other neurodevelopmental traits in the general population; thus genetic risks might plausibly also contribute to cognitive ability later in development and to educational underachievement. Methods: We generated ADHD polygenic risk scores in the Avon Longi...
44 CitationsSource
#1Eva Krapohl ('KCL': King's College London)H-Index: 20
#2Jack Euesden ('KCL': King's College London)H-Index: 13
Last. Robert Plomin ('KCL': King's College London)H-Index: 171
view all 10 authors...
Genome-wide polygenic scores (GPS), which aggregate the effects of thousands of DNA variants from genome-wide association studies (GWAS), have the potential to make genetic predictions for individuals. We conducted a systematic investigation of associations between GPS and many behavioral traits, the behavioral phenome. For 3152 unrelated 16-year-old individuals representative of the United Kingdom, we created 13 GPS from the largest GWAS for psychiatric disorders (for example, schizophrenia, de...
116 CitationsSource
#1W. David Hill (Edin.: University of Edinburgh)H-Index: 25
#2Gail Davies (Edin.: University of Edinburgh)H-Index: 68
Last. Ian J. Deary (Edin.: University of Edinburgh)H-Index: 184
view all 5 authors...
Background General cognitive function predicts psychiatric illness across the life course. This study examines the role of pleiotropy in explaining the link between cognitive function and psychiatric disorder.
64 CitationsSource
#1David T. Liebers (Johns Hopkins University)H-Index: 4
#2Mehdi Pirooznia (Johns Hopkins University)H-Index: 30
Last. Fernando S. Goes (Johns Hopkins University)H-Index: 37
view all 6 authors...
Cognitive impairment is a common feature of the major psychotic disorders, with deficits often present in at risk individuals and unaffected first-degree relatives. Previous studies have suggested that polygenic risk scores (PRS) for schizophrenia (SCZ) are associated with cognitive deficits, but there has been little examination of this association in longitudinal datasets, or comparison with other disorders. We used mixed models to study the association between PRS for 4 adult onset psychiatri...
26 CitationsSource
Cited By12
#1Sadie J. Zacharek (MIT: Massachusetts Institute of Technology)
#2Sahana Kribakaran (Yale University)H-Index: 2
Last. Dylan G. Gee (Yale University)H-Index: 32
view all 0 authors...
Abstract null null Anxiety disorders are the most prevalent psychiatric condition among youth, with symptoms commonly emerging prior to or during adolescence. Delineating neurodevelopmental trajectories associated with anxiety disorders is important for understanding the pathophysiology of pediatric anxiety and for early risk identification. While a growing literature has yielded valuable insights into the nature of brain structure and function in pediatric anxiety, progress has been limited by ...
#1Emma EveraertH-Index: 2
#2Tessel BoermaH-Index: 8
Last. Frank WijnenH-Index: 24
view all 5 authors...
Abstract In this systematic review, we investigate executive functioning (EF) in a selected population: children and adolescents with 22q11.2 Deletion Syndrome (22q11DS). Studying a selected subset of the population can inform our understanding of typical development by reducing the etiological variability associated with phenotypic expression of EF. In 22q11DS, EF deficits are, at least in part, the consequence of the deletion on chromosome 22. However, the expression of EF phenotype in 22q11DS...
#1Brian C. Kavanaugh (Brown University)H-Index: 9
#2Alexa Fryc (URI: University of Rhode Island)H-Index: 1
Last. Anthony Spirito (Brown University)H-Index: 78
view all 7 authors...
Abstract This exploratory study examined multiple units of working memory (WM) analysis in a transdiagnostic, treatment-seeking, pediatric sample. This included a) an electroencephalography marker of WM (coupling of theta and gamma oscillations [i.e., theta-gamma coupling] in frontal brain regions), b) WM test performance, and c) parent-reported WM symptoms. A composite score combining each of these units of analysis correlated with self-reported depressive and anxiety symptoms, with only theta-...
#1Vanteemar S. Sreeraj (National Institute of Mental Health and Neurosciences)H-Index: 7
#2Bharath Holla (National Institute of Mental Health and Neurosciences)H-Index: 9
Last. Biju Viswanath (National Institute of Mental Health and Neurosciences)H-Index: 18
view all 16 authors...
Syndromes of schizophrenia, bipolar disorder, obsessive-compulsive disorder, substance use disorders and Alzheimer's dementia are highly heritable. About 10-20% of subjects have another affected first degree relative (FDR), and thus represent a 'greater' genetic susceptibility. We screened 3583 families to identify 481 families with multiple affected members, assessed 1406 individuals in person, and collected information systematically about other relatives. Within the selected families, a third...
1 CitationsSource
#1Sofía Aguilar-Lacasaña (UVic-UCC: University of Vic)
Last. Silvia AlemanyH-Index: 13
view all 8 authors...
BACKGROUND Attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are child-onset neurodevelopmental disorders frequently accompanied by cognitive difficulties. In the current study, we aim to examine the genetic overlap between ADHD and ASD and cognitive measures of working memory (WM) and attention performance among schoolchildren using a polygenic risk approach. METHODS A total of 1667 children from a population-based cohort aged 7-11 years with data available ...
#1Brian C. Kavanaugh (Brown University)H-Index: 9
#2Mary Kathryn Cancilliere (URI: University of Rhode Island)H-Index: 7
Last. Anthony Spirito (Brown University)H-Index: 78
view all 9 authors...
ABSTRACTIntroduction: Despite preliminary research, there remain inconsistent findings with regard to the role of executive functioning (EF) deficits in childhood anxiety and depression. This repor...
#1Budhachandra Khundrakpam (McGill University)H-Index: 15
#2Uku Vainik (UT: University of Tartu)H-Index: 13
Last. Alan C. Evans (McGill University)H-Index: 198
view all 11 authors...
Autism spectrum disorder is a highly prevalent and highly heritable neurodevelopmental condition, but studies have mostly taken traditional categorical diagnosis approach (yes/no for autism spectrum disorder). In contrast, an emerging notion suggests a continuum model of autism spectrum disorder with a normal distribution of autistic tendencies in the general population, where a full diagnosis is at the severe tail of the distribution. We set out to investigate such a viewpoint by investigating ...
#1Amery Treble-Barna (University of Pittsburgh)H-Index: 10
#2Valentina Pilipenko (Boston Children's Hospital)H-Index: 1
Last. Brad G. Kurowski (University of Cincinnati Academic Health Center)H-Index: 1
view all 8 authors...
The addition of genetic factors to prognostic models of neurobehavioral recovery following pediatric traumatic brain injury (TBI) may account for unexplained heterogeneity in outcomes. The present ...
4 CitationsSource
#1Jamie K. Capal (UC: University of Cincinnati)H-Index: 1
#2Eric A. Macklin (Harvard University)H-Index: 48
Last. Gregory N. Barnes (University of Louisville)H-Index: 14
view all 4 authors...
BACKGROUND AND OBJECTIVES: Children with autism spectrum disorder (ASD) have a higher prevalence of epilepsy compared with general populations. In this pilot study, we prospectively identified baseline risk factors for the development of seizures in individuals with ASD and also identified characteristics sensitive to seizure onset up to 6 years after enrollment in the Autism Speaks Autism Treatment Network. METHODS: Children with ASD and no history of seizures at baseline who either experienced...
1 CitationsSource
#1Vanteemar S. Sreeraj (National Institute of Mental Health and Neurosciences)H-Index: 7
#2Bharath Holla (National Institute of Mental Health and Neurosciences)H-Index: 9
Last. Biju Viswanath (National Institute of Mental Health and Neurosciences)H-Index: 18
view all 16 authors...
Accelerator program for discovery in brain disorders using stem cells (ADBS) is an ongoing longitudinal study investigating the neurobiological aspects of five psychiatric disorders (Alzheimers dementia, bipolar disorder, obsessive-compulsive disorder, substance use disorder or schizophrenia) in India. The study uses several techniques (brain-imaging, psychophysics, neuropsychology, next-generation sequencing, cellular models), and in-depth clinical assessments in a longitudinal cohort from mult...
2 CitationsSource