EXAMINING THE SHARED ETIOLOGY OF PSYCHOPATHOLOGY WITH GENOME-WIDE ASSOCIATION STUDIES

Letter Gastroenterology & Hepatology

Global prediction of primary liver cancer incidences and mortality in 2040

Chenxi Li et al.

JOURNAL OF HEPATOLOGY (2023)

Article Neurosciences

Pervasive Downward Bias in Estimates of Liability-Scale Heritability in Genome-wide Association Study Meta-analysis: A Simple Solution

Andrew D. Grotzinger et al.

Summary: This article points out the incorrectness of the standard approach in transforming risk proportions and proposes a simple solution for obtaining more accurate estimates by incorporating cohort-specific ascertainment.

BIOLOGICAL PSYCHIATRY (2023)

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Article Neurosciences

How do substance use disorders compare to other psychiatric conditions on structural brain abnormalities? A cross-disorder meta-analytic comparison using theENIGMAconsortium findings

Xavier Navarri et al.

Summary: Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with significant brain alterations, particularly in subcortical and cortical regions. The brain abnormalities in AUD are comparable to or larger than those found in other psychiatric disorders, while CUD is most strongly related to reduced cortical thickness in the medial orbitofrontal cortex.

HUMAN BRAIN MAPPING (2022)

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Article Neurosciences

Evaluating brain structure traits as endophenotypes using polygenicity and discoverability

Nana Matoba et al.

Summary: Research findings suggest that brain structure traits have lower polygenicity and higher discoverability compared to multiple neuropsychiatric disorders, supporting their potential as endophenotypes.

HUMAN BRAIN MAPPING (2022)

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Article Environmental Sciences

Identifying periods of heightened susceptibility to lead exposure in relation to behavioral problems

Clara G. Sears et al.

Summary: The study found that higher blood lead concentrations during childhood were associated with behavioral problems, with the strongest impact seen at the age of 8. This highlights the importance of lead prevention interventions in childhood to address ADHD-related behaviors.

JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY (2022)

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Article Biochemistry & Molecular Biology

A roadmap to increase diversity in genomic studies

Segun Fatumo et al.

Summary: This article describes the factors contributing to the imbalance in representation of different populations in genetic and genomic studies, and proposes a roadmap to enhance inclusion and ensure equal health benefits of genomics advances. The authors emphasize the importance of global efforts to ensure that everyone can benefit from genomic medicine.

NATURE MEDICINE (2022)

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Editorial Material Neurosciences

Crossing diagnostic boundaries to understand the genetic etiology of addiction

Travis T. Mallard

NEUROPSYCHOPHARMACOLOGY (2022)

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Article Neurosciences

The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates

Alexander S. Hatoum et al.

Summary: Shared genetic liability partly explains susceptibility to alcohol, tobacco, cannabis, and opioid use disorders. The Addiction-Risk-Factor is associated with risk-taking, neuroticism, executive function, and non-substance psychopathology, retaining specific variance even after accounting for the genetics of substance use.

NEUROPSYCHOPHARMACOLOGY (2022)

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Review Clinical Neurology

Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings

Eun-Jin Cheon et al.

Summary: This review compares the main brain abnormalities in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 Deletion Syndrome. The findings suggest that the effect sizes of brain abnormalities are generally in the same direction and scale in severity with the disorders. Furthermore, the effect sizes for 22q11.2 Deletion Syndrome appear to be larger than for the other psychiatric disorders, which is consistent with the idea of larger effects on the brain of rare genetic variants.

PSYCHIATRY AND CLINICAL NEUROSCIENCES (2022)

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Article Multidisciplinary Sciences

Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases

Carolina Makowski et al.

Summary: Genetic variants affecting regional cortical surface area and thickness in the brain were studied in adults and children, revealing 440 significant loci. The genetic variations in adulthood were found to already be present in childhood, showing signs of negative selection and associations with early neurodevelopment and neuropsychiatric risk.

SCIENCE (2022)

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Article Psychiatry

Item-Level Genome-Wide Association Study of the Alcohol Use Disorders Identification Test in Three Population-Based Cohorts

Travis T. Mallard et al.

Summary: This study utilized genomic structural equation modeling to explore the genetics of alcohol consumption and problematic consequences as measured by the Alcohol Use Disorders Identification Test (AUDIT). Through a large-scale GWAS and multivariate approach, the authors identified genetic correlations among the AUDIT items and constructed an aggregate measure strongly associated with alcohol dependence.

AMERICAN JOURNAL OF PSYCHIATRY (2022)

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Article Psychiatry

Insulinopathies of the brain? Genetic overlap between somatic insulin-related and neuropsychiatric disorders

Giuseppe Fanelli et al.

Summary: The prevalence of somatic insulinopathies, such as metabolic syndrome, obesity, and type 2 diabetes mellitus, is higher in Alzheimer's disease, autism spectrum disorder, and obsessive-compulsive disorder. There is a genetic overlap between these neuropsychiatric disorders and insulin-related diseases/traits, indicating a potential shared genetic mechanism.

TRANSLATIONAL PSYCHIATRY (2022)

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Article Multidisciplinary Sciences

Reproducible brain-wide association studies require thousands of individuals

Scott Marek et al.

Summary: Magnetic resonance imaging (MRI) has greatly advanced our understanding of the human brain, but similar progress has not been made in mental health research. By analyzing three large neuroimaging datasets, researchers found that brain-wide association studies (BWAS) had smaller effect sizes than previously thought, leading to underpowered studies, inflated effect sizes, and replication failures. As sample sizes increased, replication rates improved and effect size inflation decreased. Functional MRI, cognitive tests, and multivariate methods showed more robust effects in BWAS. Smaller than expected brain-phenotype associations and population subsample variability explain the widespread replication failures in BWAS. Reproducibility in BWAS requires samples with thousands of individuals.

NATURE (2022)

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Article Multidisciplinary Sciences

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Vassily Trubetskoy et al.

Summary: In this study, a two-stage genome-wide association study was conducted to identify common variants associated with schizophrenia. The results revealed 287 distinct genomic loci and 120 genes likely to be involved in the development of schizophrenia. This research provides valuable insights into the pathophysiology of schizophrenia and offers a resource for further mechanistic studies.

NATURE (2022)

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Article Multidisciplinary Sciences

Rare coding variants in ten genes confer substantial risk for schizophrenia

Tarjinder Singh et al.

Summary: Rare coding variants in certain genes, particularly those related to the function of the nervous system, are found to be significantly associated with schizophrenia. The involvement of specific receptor subunits in the glutamatergic system supports the hypothesis of dysfunction in this system as a mechanism in the development of schizophrenia. The findings suggest that both common and rare genetic risk factors are involved in the pathogenesis of schizophrenia, and more risk genes are yet to be discovered using this approach.

NATURE (2022)

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Article Genetics & Heredity

Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data

Pierrick Wainschtein et al.

Summary: The analysis of whole-genome sequences of 25,465 individuals of European ancestry reveals that rare variants play a significant role in the heritability of height and body mass index.

NATURE GENETICS (2022)

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Editorial Material Genetics & Heredity

Discovering missing heritability in whole-genome sequencing data

Alexander Young

Summary: The gap between heritability estimates from twin studies and genotyping array data is largely due to rare variants, which can only be detected through whole-genome sequencing (WGS) data.

NATURE GENETICS (2022)

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Article Genetics & Heredity

Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia

Duncan S. Palmer et al.

Summary: Exome sequencing analysis of individuals with bipolar disorder reveals enrichment of ultra-rare protein-truncating variants in constrained genes. AKAP11 is identified as a risk gene for both bipolar disorder and schizophrenia. This study highlights the importance of rare coding variation in the development of bipolar disorder.

NATURE GENETICS (2022)

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Article Genetics & Heredity

An integrated framework for local genetic correlation analysis

Josefin Werme et al.

Summary: Genetic correlation analysis is used to identify phenotypes with shared genetic basis. Traditional approaches may fail in cases where the correlation is confined to specific genomic regions or shows opposing directions at different loci. The LAVA framework introduced here allows for local analysis of genetic correlation, as well as evaluation of local heritabilities and conditional genetic relations between multiple phenotypes.

NATURE GENETICS (2022)

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Article Genetics & Heredity

Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis

Andrew D. Grotzinger et al.

Summary: A joint analysis of 11 major psychiatric disorders identified four broad factors underlying the genetic correlations among the disorders, along with multiple loci acting on these factors. These findings suggest the presence of genetic overlap among different psychiatric disorders, but also highlight the heterogeneity within each factor. However, a single dimension of genetic risk does not appear to be useful in explaining the biobehavioral correlates or individual variants of psychiatric disorders.

NATURE GENETICS (2022)

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Review Neurosciences

Genomics, convergent neuroscience and progress in understanding autism spectrum disorder

Helen Rankin Willsey et al.

Summary: This article explores the genes associated with autism spectrum disorder (ASD) and discusses the use of convergent neuroscience approaches to understand the pathobiology of ASD.

NATURE REVIEWS NEUROSCIENCE (2022)

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Article Multidisciplinary Sciences

Genetic analysis of over half a million people characterises C-reactive protein loci

Saredo Said et al.

Summary: This study reports the largest genome-wide association study on C-reactive protein (CRP), a marker of chronic low-grade inflammation. The study identifies 266 independent genetic loci associated with CRP levels and highlights 42 gene sets associated with CRP. Tissue expression analysis indicates a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study and Mendelian randomisation analyses provide evidence for causal associations between genetically determined CRP and schizophrenia, chronic airway obstruction and prostate cancer.

NATURE COMMUNICATIONS (2022)

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Article Genetics & Heredity

Exploring the genetic overlap between twelve psychiatric disorders

Cato Romero et al.

Summary: The comorbidity among psychiatric disorders is supported by genetic correlations, but finding shared biological mechanisms remains challenging due to variation in power and genetic architecture between disorders.

NATURE GENETICS (2022)

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Editorial Material Multidisciplinary Sciences

Potential bias in genetic correlations Mating patterns across two traits can inflate estimates of genetic overlap

Andrew D. Grotzinger et al.

SCIENCE (2022)

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Article Multidisciplinary Sciences

Cross-trait assortative mating is widespread and inflates genetic correlation estimates

Richard Border et al.

Summary: The study introduces cross-trait assortative mating (xAM) as an alternative explanation for genetic correlations between different human traits, showing that xAM affects various phenotypes and can plausibly account for a substantial portion of genetic correlation estimates. The results suggest that previous reports may have overestimated the true genetic similarity between many phenotypes.

SCIENCE (2022)

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Article Multidisciplinary Sciences

Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD

Michael J. Gandal et al.

Summary: This study demonstrates widespread transcriptomic changes in the cerebral cortex of individuals with autism spectrum disorder (ASD), with an anterior-to-posterior gradient. These changes primarily affect gene expression in excitatory neurons and glia. Additionally, both rare and common ASD-associated genetic variations converge within specific co-expression modules involving synaptic signaling and protein chaperone genes.

NATURE (2022)

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Article Genetics & Heredity

Identifying disease-critical cell types and cellular processes by integrating single-cell RNA-sequencing and human genetics

Karthik A. Jagadeesh et al.

Summary: The study introduces a new framework called sc-linker, which integrates single-cell RNA sequencing and epigenomic data on the basis of genome-wide association studies to infer the cell types and processes by which genetic variants influence disease.

NATURE GENETICS (2022)

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Article Multidisciplinary Sciences

Mendelian randomization

Eleanor Sanderson et al.

Summary: Mendelian randomization (MR) uses genetic variation to address causal questions about modifiable exposures, with principles based on Mendel's laws and instrumental variable estimation methods. It enables inference of causal effects and can be used as part of a triangulation across multiple sources of evidence for causal inference.

NATURE REVIEWS METHODS PRIMERS (2022)

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Article Biochemistry & Molecular Biology

Educational attainment impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study with ~780,000 participants

Daniel B. Rosoff et al.

Summary: Genetic instruments associated with increased educational attainment are linked to reduced risk of alcohol dependence, but may also lead to higher alcohol intake frequency.

MOLECULAR PSYCHIATRY (2021)

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Article Psychology, Clinical

Dissociable hormonal profiles for psychopathology and stress in anorexia and bulimia nervosa

Margaret L. Westwater et al.

Summary: Anorexia nervosa (AN) and bulimia nervosa (BN) are complex psychiatric conditions, with stress playing a role in triggering loss-of-control eating behaviors. While stress increases acyl-ghrelin and PYY in AN, it does not alter gut hormone profiles in BN. Additionally, psychological stress can disrupt homeostatic signaling in AN, potentially contributing to the maintenance of disordered eating in this serious illness.

PSYCHOLOGICAL MEDICINE (2021)

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Article Psychiatry

Pervasively Thinner Neocortex as a Transdiagnostic Feature of General Psychopathology

Adrienne L. Romer et al.

Summary: Neuroimaging research suggests that pervasive reductions in neocortical thickness are common across all forms of mental disorders, indicating a transdiagnostic feature of general psychopathology. The underlying brain structural correlates of mental disorders may lack specificity, and pursuing such specific correlates could limit progress towards effective strategies for understanding, preventing, and intervening in mental disorders.

AMERICAN JOURNAL OF PSYCHIATRY (2021)

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Review Psychology

Reports of My Death Were Greatly Exaggerated: Behavior Genetics in the Postgenomic Era

K. Paige Harden

Summary: Behavior genetics studies the influence of genetic differences on psychology and behavior, with advancements in measuring the human genome revealing new insights into gene-environment interactions, heritability, and other aspects of genetic research.

ANNUAL REVIEW OF PSYCHOLOGY, VOL 72 (2021)

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Article Neurosciences

Investigation of glycaemic traits in psychiatric disorders using Mendelian randomisation revealed a causal relationship with anorexia nervosa

Danielle M. Adams et al.

Summary: This study used genetic variants as instrumental variables to investigate the causal effect of glycemic traits on psychiatric disorders. A protective effect of an increase in fasting insulin levels on anorexia nervosa was observed, but no consistent causal effect was found for the other seven psychiatric disorders considered. Further research is needed to explore the relationship between insulin levels and anorexia.

NEUROPSYCHOPHARMACOLOGY (2021)

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Article Neurosciences

Investigating Shared Genetic Basis Across Tourette Syndrome and Comorbid Neurodevelopmental Disorders Along the Impulsivity-Compulsivity Spectrum

Zhiyu Yang et al.

Summary: The study investigates the shared genetic basis across TS, ADHD, ASD, and OCD, revealing a common unifying factor connecting TS, ADHD, and ASD, while showing the highest genetic correlation between TS and OCD. Through a systematic meta-analysis, multiple novel hits and regions have been identified, indicating pleiotropic roles for specific disorders analyzed here. The study underlines the importance of redefining the framework for research across traditional diagnostic categories.

BIOLOGICAL PSYCHIATRY (2021)

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Article Substance Abuse

Genomic relationships across psychiatric disorders including substance use disorders

Abdel Abdellaoui et al.

Summary: The study investigated genetic associations and latent genetic structure among psychiatric disorders, finding significant genetic correlations between alcohol and nicotine dependence with other disorders, while cannabis use disorder was only associated with ADHD. Including substance use disorders in the factor analysis led to changes in the underlying genetic factor structure, emphasizing the importance of cautious interpretation of the identified structures.

DRUG AND ALCOHOL DEPENDENCE (2021)

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Article Biotechnology & Applied Microbiology

Characterizing the effect of background selection on the polygenicity of brain-related traits

Frank R. Wendt et al.

Summary: The study demonstrates that risk locus effect sizes with larger variance in brain-related phenotypes are associated with loci under BGS. Furthermore, diagnostic complexity may contribute to the increased polygenicity of psychiatric disorders.

GENOMICS (2021)

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Article Biochemistry & Molecular Biology

Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders

Nevena V. Radonjic et al.

Summary: Genomewide association studies have shown significant genetic correlations among neuropsychiatric disorders. The study found substantial similarities in structural brain alterations among disorders, hinting at a shared genetic etiology. These similarities in brain alterations appear to be partially explained by common genetic variants.

MOLECULAR PSYCHIATRY (2021)

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Article Genetics & Heredity

Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk

Christopher Y. Park et al.

Summary: The research revealed the crucial role of RNA-binding proteins (RBPs) in psychiatric disorder risk, with the pathogenic contribution of noncoding variants impacting RBP target sites being a key factor. RBP dysregulation explains a significant amount of heritability not captured by large-scale studies and has a stronger impact.

NATURE GENETICS (2021)

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Article Psychiatry

Investigating the effects of genetic risk of schizophrenia on behavioural traits

Adam Socrates et al.

Summary: The study found that higher schizophrenia polygenic risk scores were associated with lower verbal-numerical reasoning, higher nervous feelings, and higher self-reported risk-taking. Further analysis suggested that these risk traits may be related to genetic propensity for risk-taking leading to greater migration, urbanicity, or drug-taking behaviors.

NPJ SCHIZOPHRENIA (2021)

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Article Neurosciences

DCC gene network in the prefrontal cortex is associated with total brain volume in childhood

Alice Morgunova et al.

Summary: The study found that the DCC coexpression network in the prefrontal cortex plays a critical role in whole brain development during the first decade of life. Genes comprising the ePRS are mainly involved in regulating cellular function, and the ePRS is positively correlated with total brain volume in children.

JOURNAL OF PSYCHIATRY & NEUROSCIENCE (2021)

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Article Genetics & Heredity

Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in the Million Veteran Program

Murray B. Stein et al.

Summary: In this study, genome-wide association analyses were conducted on over 250,000 participants of European and African ancestry using electronic health record-validated PTSD diagnosis. Significant loci were identified in both European case-control analyses and quantitative symptom analyses. The results validate the biological coherence of PTSD syndrome, highlight its relationship with comorbid anxiety and depressive disorders, and offer new considerations for treatment.

NATURE GENETICS (2021)

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Article Neurosciences

Long-term maturation of human cortical organoids matches key early postnatal transitions

Aaron Gordon et al.

Summary: Research shows that three-dimensional human cortical organoids can reach stages of postnatal brain development after being cultured for 250 to 300 days, paralleling in vivo development. These findings provide important insights and tools for modeling neurodevelopmental diseases.

NATURE NEUROSCIENCE (2021)

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Article Genetics & Heredity

Genetic analyses identify widespread sex-differential participation bias

Nicola Pirastu et al.

Summary: Genetic analyses have revealed widespread sex-differential participation bias in population-based studies, potentially leading to incorrect inferences; the study demonstrated artifactual autosomal heritability of sex in the presence of sex-differential participation bias; through conducting a genome-wide association study contrasting one subgroup versus another, it is possible to estimate comparative biases.

NATURE GENETICS (2021)

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Article Genetics & Heredity

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Niamh Mullins et al.

Summary: A genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry revealed 64 associated genomic loci, enriched in genes related to synaptic signaling pathways and brain-expressed genes. The study also identified potential therapeutic leads and drug targets, highlighting the complex genetic correlations between bipolar disorder subtypes and providing insights into the disorder's etiology.

NATURE GENETICS (2021)

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Review Psychology, Clinical

Shared genetic architecture across psychiatric disorders

Andrew D. Grotzinger

Summary: Psychiatric disorders show substantial genetic overlap, with over a hundred genetic variants identified that affect multiple disorders and more to be uncovered as sample sizes continue to grow. Psychiatric genomics has made rapid progress in the last decade, shedding light on the biological makeup of cross-disorder risk.

PSYCHOLOGICAL MEDICINE (2021)

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Article Psychology, Biological

Symptom-level modelling unravels the shared genetic architecture of anxiety and depression

Jackson G. Thorp et al.

Summary: Using factor analysis and genomic structural equation modelling, this study investigated the genetic factor structure underlying depression, anxiety, and neuroticism and conducted genome-wide association analyses to identify a high genetic correlation between depressive and anxiety symptoms. Validation in a cohort of approximately 1.9 million individuals confirmed the reliability of the results, revealing shared and trait-specific genetic associations between depression and anxiety.

NATURE HUMAN BEHAVIOUR (2021)

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Article Genetics & Heredity

The distribution of common-variant effect sizes

Luke J. O'Connor

Summary: The genetic effect-size distribution of a disease, which includes the number of risk variants, their effect sizes, and sample sizes required to discover them, can be accurately estimated using Fourier Mixture Regression (FMR). FMR estimates that 100,000-1,000,000 cases will be needed to find genome-wide significant SNPs explaining 50% of SNP heritability. In large studies, genome-wide significance becomes more conservative and less stringent thresholds can achieve high true positive rates if confounding is controlled.

NATURE GENETICS (2021)

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Article Neurosciences

Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions

Daniel F. Levey et al.

Summary: This study identified 178 risk variants for major depressive disorder, advancing understanding of its biology and hinting at new treatment possibilities. The research sheds light on the genetic architecture of depression and provides new insight into the interrelatedness of complex psychiatric traits.

NATURE NEUROSCIENCE (2021)

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Article Neurosciences

Coexpression network architecture reveals the brain-wide and multiregional basis of disease susceptibility

Christopher L. Hartl et al.

Summary: By leveraging RNA sequencing data, researchers were able to identify brain-wide, cross-regional, and region-specific coexpression modules. Genetic risk for schizophrenia and autism was enriched in brain-wide and multiregional modules, indicating broad impact.

NATURE NEUROSCIENCE (2021)

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Review Neurosciences

Neurodevelopment of the association cortices: Patterns, mechanisms, and implications for psychopathology

Valerie J. Sydnor et al.

Summary: The development of the human brain cortex is a prolonged process that progresses from lower-order functions to higher-order functions, conforming to a hierarchical pattern of organization. This developmental program enhances feature variation between different regions, but also carries risks for diverse developmental psychopathologies.

NEURON (2021)

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Review Psychology, Clinical

Using Mendelian randomization analysis to better understand the relationship between mental health and substance use: a systematic review

Jorien L. Treur et al.

Summary: The study found significant associations between educational attainment and smoking rates, as well as alcohol consumption frequency, indicating potential causal relationships. Additionally, a bi-directional relationship was observed between smoking and mental disorders. The findings suggest that mental disorders causally lead to increased alcohol consumption, while alcohol consumption does not have a significant reverse effect on mental disorders.

PSYCHOLOGICAL MEDICINE (2021)

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Article Multidisciplinary Sciences

Protein-coding repeat polymorphisms strongly shape diverse human phenotypes

Ronen E. Mukamel et al.

Summary: This study utilized whole-exome sequencing data to estimate VNTR lengths and impute VNTR alleles into single-nucleotide polymorphism haplotypes, identifying strong associations of common variants with human phenotypes like height, hair morphology, and biomarkers of health. Accounting for large-effect VNTRs enabled further fine-mapping of associations to many more protein-coding mutations in the same genes. These findings point to hidden effects of highly polymorphic common structural variants that have not been previously analyzed at the molecular level.

SCIENCE (2021)

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Article Neurosciences

Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction

Richard Karlsson Linner et al.

Summary: Research shows that persistent difficulties in self-regulation may be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates. By leveraging genetic correlations, over 500 genetic loci related to externalizing traits were identified, enriched for genes expressed in the brain and related to nervous system development.

NATURE NEUROSCIENCE (2021)

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Review Multidisciplinary Sciences

Genome-wide association studies

Emil Uffelmann et al.

Summary: Genome-wide association studies (GWAS) involve testing hundreds of thousands of genetic variants to identify those associated with specific traits or diseases, with the number of associated variants expected to increase as sample sizes grow. The results of GWAS have various applications, including understanding the underlying biology of phenotypes, estimating heritability, predicting clinical risks, guiding drug development programs, and inferring causal relationships between risk factors and health outcomes.

NATURE REVIEWS METHODS PRIMERS (2021)

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Article Psychology, Clinical

Synaptic and brain-expressed gene sets relate to the shared genetic risk across five psychiatric disorders

Anke R. Hammerschlag et al.

PSYCHOLOGICAL MEDICINE (2020)

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Article Biochemistry & Molecular Biology

The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

Daniel E. Vosberg et al.

MOLECULAR PSYCHIATRY (2020)

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Article Psychiatry

Reproducible Genetic Risk Loci for Anxiety: Results From similar to 200,000 Participants in the Million Veteran Program

Daniel F. Levey et al.

AMERICAN JOURNAL OF PSYCHIATRY (2020)

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Article Biochemistry & Molecular Biology

Association of lead-exposure risk and family income with childhood brain outcomes

Andrew T. Marshall et al.

NATURE MEDICINE (2020)

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Article Neurosciences

Cross-Disorder Analysis of Brain Structural Abnormalities in Six Major Psychiatric Disorders: A LSecondary Analysis of Mega- and Meta-analytical Findings From the ENIGMA Consortium

Nils Opel et al.

BIOLOGICAL PSYCHIATRY (2020)

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Review Neurosciences

The Netrin-1/DCC Guidance Cue Pathway as a Molecular Target in Depression: Translational Evidence

Angelica Torres-Berrio et al.

BIOLOGICAL PSYCHIATRY (2020)

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Article Medicine, General & Internal

Mechanisms linking childhood trauma exposure and psychopathology: a transdiagnostic model of risk and resilience

Katie A. McLaughlin et al.

BMC MEDICINE (2020)

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Article Multidisciplinary Sciences

The genetic architecture of the human cerebral cortex

Katrina L. Grasby et al.

SCIENCE (2020)

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Article Genetics & Heredity

A cross-disorder PRS-pheWAS of 5 major psychiatric disorders in UK Biobank

Beate Leppert et al.

PLOS GENETICS (2020)

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Article Biochemistry & Molecular Biology

Glycobiology and schizophrenia: a biological hypothesis emerging from genomic research

Robert G. Mealer et al.

MOLECULAR PSYCHIATRY (2020)

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Article Neurosciences

Emerging phenotyping strategies will advance our understanding of psychiatric genetics

Sandra Sanchez-Roige et al.

NATURE NEUROSCIENCE (2020)

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Article Neurosciences

A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles

Nancy Y. A. Sey et al.

NATURE NEUROSCIENCE (2020)

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Review Behavioral Sciences

Neurodevelopmental pathways in bipolar disorder

Stefan Kloiber et al.

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS (2020)

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Review Biochemical Research Methods

Tutorial: a guide to performing polygenic risk score analyses

Shing Wan Choi et al.

NATURE PROTOCOLS (2020)

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Article Multidisciplinary Sciences

The GTEx Consortium atlas of genetic regulatory effects across human tissues

Francois Aguet et al.

SCIENCE (2020)

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Article Psychiatry

Testing structural models of psychopathology at the genomic level

Irwin D. Waldman et al.

WORLD PSYCHIATRY (2020)

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Editorial Material Psychiatry

Using genetic information to inform policy on cannabis

Lindsey A. Hines et al.

LANCET PSYCHIATRY (2020)

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Article Psychiatry

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Emma C. Johnson et al.

LANCET PSYCHIATRY (2020)

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Review Biochemistry & Molecular Biology

Psychiatric genetics and the structure of psychopathology

Jordan W. Smoller et al.

MOLECULAR PSYCHIATRY (2019)

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Review Biochemistry & Molecular Biology

A decade in psychiatric GWAS research

Tanya Horwitz et al.

MOLECULAR PSYCHIATRY (2019)

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Review Biochemistry & Molecular Biology

Defining the Genetic, Genomic, Cellular, and Diagnostic Architectures of Psychiatric Disorders

Patrick F. Sullivan et al.

CELL (2019)

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Article Genetics & Heredity

Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways

Philip R. Jansen et al.

NATURE GENETICS (2019)

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