Review
Biochemistry & Molecular Biology
Monika A. Waszczuk, Katherine G. Jonas, Marina Bornovalova, Gerome Breen, Cynthia M. Bulik, Anna R. Docherty, Thalia C. Eley, John M. Hettema, Roman Kotov, Robert F. Krueger, Todd Lencz, James J. Li, Evangelos Vassos, Irwin D. Waldman
Summary: Genome-wide association studies (GWAS) have the potential to provide biological insights into disease mechanisms and offer clinically useful biomarkers. This review examines the use of quantitative and transdiagnostic phenotypes in GWAS for major psychiatric disorders. The authors discuss themes and recommendations, including issues of sample size, phenotypic reliability, sources of phenotypic information, and the use of biological and behavioral markers. The review also highlights the importance of multi-trait methods and the potential of dimensional and transdiagnostic phenotypes for gene discovery in psychiatric conditions.
MOLECULAR PSYCHIATRY
(2023)
Review
Psychology, Biological
Abdel Abdellaoui, Karin J. H. Verweij
Summary: Genome-wide association studies on human behavioural traits are generating large amounts of polygenic signals with significant predictive power and potentially useful biological clues. Behavioural traits, being more distal and less directly under biological control compared to physical characteristics, present challenges in interpreting the associated genetic effects. Research results likely consist of a composite of signals from various sources, and additional steps are needed to better understand and interpret the increasingly strong polygenic signals.
NATURE HUMAN BEHAVIOUR
(2021)
Article
Multidisciplinary Sciences
Peitao Wu, Biqi Wang, Steven A. Lubitz, Emelia J. Benjamin, James B. Meigs, Josee Dupuis
Summary: This study proposes an approximate conditional phenotype analysis method based on GWAS summary statistics, covariance between traits, and variant minor allele frequency. The method shows high consistency and accuracy in estimating genetic effect size compared to individual level data analysis, providing an efficient way to perform conditional analysis using large-scale GWAS summary statistics.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jack W. O'Sullivan, John P. A. Ioannidis
Summary: This study compared SNVs from earlier and later GWAS and found a replication rate of 85.0% in subsequent studies, with a lower replication rate for binary phenotypes compared to quantitative phenotypes. The study also identified a decrease in SNV effect size for binary phenotypes, but an increase for quantitative phenotypes, and developed a model that could predict SNV replication effectively.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jose Jaime Martinez-Magana, Alma Delia Genis-Mendoza, Jorge Ameth Villatoro Velazquez, Marycarmen Bustos-Gamino, Isela Esther Juarez-Rojop, Carlos Alfonso Tovilla-Zarate, Emmanuel Sarmiento, Erasmo Saucedo, Oscar Rodriguez-Mayoral, Clara Fleiz-Bautista, Beatriz Camarena, Alejandro Aguilar, Thelma Beatriz Gonzalez-Castro, Maria Elena Medina-Mora, Humberto Nicolini
Summary: The study revealed common comorbidities of substance use and psychiatric disorders in the Mexican population with genome-wide correlations and vertical pleiotropy. Although no genome-wide association signals were identified, specific SNPs were independently associated with each trait, and individuals with high PRS had higher prevalence of substance use disorders.
SCIENTIFIC REPORTS
(2021)
Review
Plant Sciences
Laura Tibbs Cortes, Zhiwu Zhang, Jianming Yu
Summary: Genome-wide association studies (GWAS) have become a powerful tool for investigating complex traits, with the development of the mixed model framework reducing false positives. Advances in technology have led to the development of methods to increase computational speed or improve statistical power in GWAS.
Article
Multidisciplinary Sciences
Ludivine Obry, Cyril Dalmasso
Summary: In this study, we evaluated recent weighted multiple testing procedures for genome wide association studies (GWAS) through a simulation study. We also introduced a new efficient procedure called wBHa, which prioritizes the detection of genetic variants with low minor allel frequencies while maximizing overall detection power. Our results demonstrated that wBHa outperformed other procedures in detecting rare variants while maintaining good overall power.
Article
Biochemical Research Methods
Richard J. Packer, Alex T. Williams, William Hennah, Micaela T. Eisenberg, Nick Shrine, Katherine A. Fawcett, Willow Pearson, Anna L. Guyatt, Ahmed Edris, Edward J. Hollox, Mikko Marttila, Balasubramanya S. Rao, John Raymond Bratty, Louise Wain, Frank Dudbridge, Martin D. Tobin
Summary: DeepPheWAS is an R package that allows for phenome-wide association studies by creating curated composite phenotypes and integrating quantitative phenotypes from primary care data, as well as disease progression and drug response phenotypes. It provides tools for efficient analysis of associations with genetic input under any genetic model, including optional sex-stratified analysis and phenotype development.
Article
Computer Science, Interdisciplinary Applications
Xinyue Wang, Xiaoqian Jiang, Jaideep Vaidya
Summary: The paper proposes two algorithms for generating synthetic SNPs that are indistinguishable from real SNPs. Through game theoretic analysis, it demonstrates the possibility of incentivizing honest behavior by the server. Extensive experiments show that the proposed method can ensure efficient and trustworthy outsourcing of logistic regression for GWAS.
JOURNAL OF BIOMEDICAL INFORMATICS
(2021)
Article
Multidisciplinary Sciences
Matteo Sesia, Stephen Bates, Emmanuel Candes, Jonathan Marchini, Chiara Sabatti
Summary: The study introduces a comprehensive statistical framework for analyzing data from genome-wide association studies of polygenic traits, demonstrating validity and effectiveness through simulations and applications to the UK Biobank data. The method outperforms state-of-the-art alternatives and is supported by comparisons with other studies, offering researchers fast software for analyzing Biobank-scale datasets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Xiaoyu Liang, Xuewei Cao, Qiuying Sha, Shuanglin Zhang
Summary: The article introduces a novel multivariate method for phenome-wide association studies (PheWAS) and demonstrates its superiority through extensive simulation studies and real-life application. The proposed method involves hierarchical clustering, clustering linear combination, and false discovery rate control steps.
Article
Food Science & Technology
Honghai Yan, Di Deng, Pingping Zhou, Yun Peng, Xiaolong Dong, Shuchang Li, Yongjie Zhang, Qin Man, Ziqin Lv, Tao Chen, Changzhong Ren, Yuanying Peng
Summary: Grain weight and size are critical traits that determine oat yield and quality. This study identified highly heritable variation in these traits and found that modern cultivars have improved grain weight and width compared to traditional oats. Genome-wide association study identified 18 loci associated with these traits and candidate genes related to ubiquitin pathway and cell division and differentiation.
JOURNAL OF CEREAL SCIENCE
(2023)
Article
Genetics & Heredity
Adrian I. Campos, Shinichi Namba, Shu-Chin Lin, Kisung Nam, Julia Sidorenko, Huanwei Wang, Yoichiro Kamatani, Ling-Hua Wang, Seunggeun Lee, Yen-Feng Lin, Yen-Chen Anne Feng, Yukinori Okada, Peter M. Visscher, Loic Yengo
Summary: Simulations and applications to real data show that adjustment of genome-wide association analyses for polygenic scores increases the statistical power for discovery across all ancestries, suggesting an analytical strategy for future studies in underrepresented populations.
Article
Biochemistry & Molecular Biology
Michael Wainberg, Daniele Merico, Matthew C. Keller, Eric B. Fauman, Shreejoy J. Tripathy
Summary: This study introduces a causal gene prioritization method, PsyOPS, specifically designed for psychiatric GWAS loci. Despite its simple form, PsyOPS achieves state-of-the-art performance compared to prior methods. Genes prioritized by PsyOPS have a higher likelihood of direct regulation by GWAS variants, supported by experimental evidence.
MOLECULAR PSYCHIATRY
(2022)
Review
Biochemistry & Molecular Biology
Imane Lalami, Carole Abo, Bruno Borghese, Charles Chapron, Daniel Vaiman
Summary: This review discusses the genetics of endometriosis, a common feminine disease with a genetic heritability estimated at around 50%. Large GWAS studies have identified some genes and loci associated with the disease, but a significant portion of the heritability remains unexplained. Additional efforts such as exome sequencing may be needed to fully elucidate the genetic factors of endometriosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Psychology, Developmental
Katie J. S. Lewis, Joanna Martin, Alice M. Gregory, Richard Anney, Anita Thapar, Kate Langley
Summary: This study examined the transmission of polygenic liability for sleep phenotypes in parents of children with ADHD, its association with comorbid sleep disturbances, and the relationship between ADHD genetic risk and sleep disturbances. The results showed that children with ADHD do not inherit polygenic liability for insomnia or chronotype differentially, but they do inherit a higher genetic risk for long sleep duration. However, there was no association between polygenic liability for insomnia, sleep duration, ADHD, and comorbid sleep disturbances. This suggests that sleep disturbances in children with ADHD may have a different etiology compared to sleep phenotypes in the general population and do not indicate a greater burden of ADHD genetic risk.
EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
(2023)
Article
Psychiatry
Silvia Colonna, Olga Eyre, Sharifah Shameem Agha, Anita Thapar, Stephanie van Goozen, Kate Langley
Summary: In individuals with ADHD, irritability was not significantly associated with cool executive functions nor with hot executive functions, contradicting the initial hypothesis.
Article
Public, Environmental & Occupational Health
Robyn E. Wootton, Lucy Riglin, Rachel Blakey, Jessica Agnew-Blais, Arthur Caye, Tim Cadman, Alexandra Havdahl, Helen Goncalves, Ana M. B. Menezes, Fernando C. Wehrmeister, Kaili Rimfeld, George Davey Smith, Thalia C. Eley, Luis Augusto Rohde, Louise Arseneault, Terrie E. Moffitt, Evie Stergiakouli, Anita Thapar, Kate Tilling
Summary: The background trajectories of ADHD traits from early childhood to mid-life in general populations show a decline over time, with variations in different measures, cohorts, and countries. Females consistently have lower average scores than males, although the sex difference decreases with age due to a steeper decrease in males.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2022)
Article
Neurosciences
Joanna Martin, Matthew Wray, Sharifah Shameem Agha, Katie J. S. Lewis, Richard J. L. Anney, Michael C. O'Donovan, Anita Thapar, Kate Langley
Summary: This study examined the direct and indirect effects of polygenic risk for neurodevelopmental and psychiatric disorders on attention-deficit/hyperactivity disorder (ADHD). The results showed that polygenic liability for ADHD and cognitive ability is directly transmitted from parents to offspring, while other disorders do not show overtransmission. In addition, nontransmitted parental alleles do not contribute indirectly to ADHD through genetic nurture. Furthermore, incomplete ADHD trios differ in demographic and clinical factors compared to complete trios.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Narun Pat, Yue Wang, Richard Anney, Lucy Riglin, Anita Thapar, Argyris Stringaris
Summary: This study aimed to develop brain-based predictive models for stable cognitive abilities during adolescence while accounting for the relationships between cognitive abilities and socio-demographic, psychological, and genetic factors. The models showed stability and generalizability, partially explaining variance in childhood cognition. The use of opportunistic stacking reduced data exclusion due to missing values. Fronto-parietal networks were found to drive childhood cognition prediction. The models also partially accounted for variance in childhood cognition due to socio-demographic, psychological, and genetic factors.
HUMAN BRAIN MAPPING
(2022)
Review
Psychology, Developmental
Anita Thapar, Lucy A. Livingston, Olga Eyre, Lucy Riglin
Summary: Young people with neurodevelopmental disorders, such as ADHD and ASD, often experience mental health problems, with depression being the most common. It is important for clinicians to understand how to assess, identify, and treat depression in the context of these disorders. This article provides an overview of the latest research on depression in young people with ADHD and ASD, including the possible mechanisms underlying the link between ADHD/ASD and depression, as well as the presentation, assessment, and treatment of depression in these disorders. The findings have important implications for clinicians and highlight the need for future research in this area.
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
(2023)
Article
Psychology, Developmental
Luiza K. Axelrud, Mauricio S. Hoffmann, Daniel E. Vosberg, Marcos Santoro, Pedro M. Pan, Ary Gadelha, Sintia Belangero, Euripedes C. Miguel, Jean Shin, Anita Thapar, Jordan W. Smoller, Zdenka Pausova, Luis A. Rohde, Matthew C. Keller, Tomas Paus, Giovanni A. Salum
Summary: This study aimed to investigate the influence of parental genetics on offspring cognition, educational attainment, and psychopathology. The findings suggest that parental genetics influence offspring outcomes through genetic and phenotypic pathways, and multiple mediations may be an effective approach for understanding intergenerational transmission of behavioral traits.
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
(2023)
Article
Psychology, Developmental
Alice Stephens, Judith Allardyce, Bryony Weavers, Jessica Lennon, Rhys Bevan Jones, Victoria Powell, Olga Eyre, Robert Potter, Valentina Escott Price, David Osborn, Anita Thapar, Stephan Collishaw, Ajay Thapar, Jon Heron, Frances Rice
Summary: A risk prediction model was developed to successfully discriminate adolescents who developed major depressive disorder (MDD) from those who did not. The model could be further developed into a tool to target individuals for low-intensity, selective preventive intervention.
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
(2023)
Article
Psychiatry
Amy Shakeshaft, Rachel Blakey, Alex S. F. Kwong, Lucy Riglin, George Davey Smith, Evie Stergiakouli, Kate Tilling, Anita Thapar
Summary: The COVID-19 pandemic had a negative impact on the mental health of individuals with neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). A study using data from the Avon Longitudinal Study of Parents and Children examined the effects of the pandemic on anxiety, depression, and mental wellbeing in adults with NDDs. The study found that individuals with ADHD and ASD had higher rates of depression, anxiety, and poor mental wellbeing compared to those without these disorders. The pandemic had a greater impact on anxiety levels in individuals with ADHD and ASD, while depressive symptoms decreased, particularly in females with ASD. Overall, mental wellbeing decreased for all participants, but to a lesser extent in those with ADHD and females with ASD.
JOURNAL OF PSYCHIATRIC RESEARCH
(2023)
Article
Genetics & Heredity
Ditte Demontis, G. Bragi Walters, Georgios Athanasiadis, Raymond Walters, Karen Therrien, Trine Tollerup Nielsen, Leila Farajzadeh, Georgios Voloudakis, Jaroslav Bendl, Biau Zeng, Wen Zhang, Jakob Grove, Thomas D. Als, Jinjie Duan, F. Kyle Satterstrom, Jonas Bybjerg-Grauholm, Marie Baekved-Hansen, Olafur O. Gudmundsson, Sigurdur H. Magnusson, Gisli Baldursson, Katrin Davidsdottir, Gyda S. Haraldsdottir, Esben Agerbo, Gabriel E. Hoffman, Soren Dalsgaard, Joanna Martin, Marta Ribases, Dorret Boomsma, Maria Soler Artigas, Nina Roth Mota, Daniel Howrigan, Sarah E. Medland, Tetyana Zayats, Veera M. Rajagopal, Merete Nordentoft, Ole Mors, David M. Hougaard, Preben Bo Mortensen, Mark J. Daly, Stephen Faraone, Hreinn Stefansson, Panos Roussos, Barbara Franke, Thomas Werge, Benjamin M. Neale, Kari Stefansson, Anders D. Borglum
Summary: This study conducted a meta-analysis of genome-wide association studies on ADHD and identified 27 significant genetic loci associated with ADHD. They also found that these loci were enriched with genes involved in early brain development. Moreover, they discovered an increased load of rare protein-truncating variants in ADHD, implicating SORCS3 as a potential gene involved in ADHD.
Review
Psychology, Developmental
P. Santosh, S. Cortese, C. Hollis, S. Bolte, D. Daley, D. Coghill, M. Holtmann, E. J. S. Sonuga-Barke, J. Buitelaar, T. Banaschewski, A. Stringaris, M. Doepfner, S. Van der Oord, S. Carucci, D. Brandeis, P. Nagy, M. Ferrin, D. Baeyens, B. J. van den Hoofdakker, D. Purper-Ouakil, A. Ramos-Quiroga, M. Romanos, C. A. Soutullo, A. Thapar, I. C. K. Wong, A. Zuddas, C. Galera, E. Simonoff
Summary: The COVID-19 pandemic has led to changes in ADHD services, with remote assessments being widely adopted. However, there is a lack of clear guidance on how to conduct these assessments effectively. Therefore, the European ADHD Guidelines Group discusses the strengths and weaknesses of remote assessments and provides recommendations for future studies and clinical practice.
EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
(2023)
Article
Psychiatry
Amy J. Lynham, Sarah Knott, Jack F. G. Underwood, Leon Hubbard, Sharifah S. Agha, Jonathan I. Bisson, Marianne B. M. van den Bree, Samuel J. R. A. Chawner, Nicholas Craddock, Michael O'Donovan, Ian R. Jones, George Kirov, Kate Langley, Joanna Martin, Frances Rice, Neil P. Roberts, Anita Thapar, Richard Anney, Michael J. Owen, Jeremy Hall, Antonio F. F. Pardinas, James T. R. Walters
Summary: The aim of this study is to develop procedures for curating and aggregating genotypic and phenotypic data in psychiatric research to investigate the relationship between shared symptoms and shared genetic liability. DRAGON-Data is a resource that combines genetic and non-genetic information and can be used for research across traditional psychiatric diagnostic categories.
Article
Mathematics, Interdisciplinary Applications
Susanne Bruins, Jouke-Jan Hottenga, Michael C. Neale, Rene Pool, Dorret I. Boomsma, Conor V. Dolan
Summary: Genotype-environment interaction refers to the moderation of genetic effects by the environment or environmental effects by genes on a phenotype. This article introduces genotype-environment interaction models and proposes a test based on the classical twin design. Simulation studies and empirical data analysis demonstrate the feasibility of this approach for detecting genotype-environment interaction, although its power depends on the heritability of the phenotype and the strength of genetic effects.
MULTIVARIATE BEHAVIORAL RESEARCH
(2023)
Article
Psychology, Clinical
Lucy Riglin, Andrew Todd, Rachel Blakey, Amy Shakeshaft, Evie Stergiakouli, George Davey Smith, Kate Tilling, Anita Thapar
Summary: This study found that persistent attention-deficit/hyperactivity disorder (ADHD) is associated with negative social outcomes, such as being not in education, employment, or training (NEET) and receiving state benefits, at age 25. The findings emphasize the importance of continued monitoring and management of ADHD symptoms and related social and clinical outcomes throughout development into adulthood.
JOURNAL OF CLINICAL PSYCHIATRY
(2023)
Letter
Medicine, General & Internal
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