ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

Translational Psychiatry, Journal Year: 2020, Volume and Issue: 10(1)

Published: March 20, 2020

Abstract This review summarizes the last decade of work by ENIGMA ( E nhancing N euro I maging G enetics through M eta A nalysis) Consortium, a global alliance over 1400 scientists across 43 countries, studying human brain in health and disease. Building on large-scale genetic studies that discovered first robustly replicated loci associated with metrics, has diversified into 50 working groups (WGs), pooling worldwide data expertise to answer fundamental questions neuroscience, psychiatry, neurology, genetics. Most WGs focus specific psychiatric neurological conditions, other study normal variation due sex gender differences, or development aging; still develop methodological pipelines tools facilitate harmonized analyses “big data” (i.e., epigenetic data, multimodal MRI, electroencephalography data). These international efforts have yielded largest neuroimaging date schizophrenia, bipolar disorder, major depressive post-traumatic stress substance use disorders, obsessive-compulsive attention-deficit/hyperactivity autism spectrum epilepsy, 22q11.2 deletion syndrome. More recent formed anxiety suicidal thoughts behavior, sleep insomnia, eating irritability, injury, antisocial personality conduct dissociative identity disorder. Here, we summarize ENIGMA’s activities ongoing projects, describe successes challenges encountered along way. We highlight advantages collaborative coordinated for testing reproducibility robustness findings, offering opportunity identify systems involved clinical syndromes diverse samples genetic, environmental, demographic, cognitive, psychosocial factors.

Language: Английский

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Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(35)

Published: Aug. 23, 2022

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- language-related skills are influenced by genetic variation, with twin-based heritability estimates 30 to 80% depending on the trait. architecture complex, heterogeneous, multifactorial, but investigations contributions single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present multicohort genome-wide association study (GWAS) five traits assessed individually using psychometric measures (word reading, nonword spelling, phoneme awareness, repetition) samples 13,633 33,959 participants aged 5 26 y. identified significant word reading (rs11208009,

Language: Английский

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What we learn about bipolar disorder from large‐scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Human Brain Mapping, Journal Year: 2020, Volume and Issue: 43(1), P. 56 - 82

Published: July 29, 2020

Abstract MRI‐derived brain measures offer a link between genes, the environment and behavior have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD underpowered, leading to varied results uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed 2012 empower discoveries, generate consensus findings inform future hypothesis‐driven BD. Through this effort, over 150 researchers from 20 countries 55 institutions pool data resources produce largest ever conducted. ENIGMA applies standardized processing analysis techniques large‐scale meta‐ mega‐analyses multimodal MRI improve replicability relating variation clinical genetic data. Initial reveal widespread patterns lower cortical thickness, subcortical volume disrupted white matter integrity associated with Findings also include mapping alterations common medications like lithium, symptom risk profiles provided further insights into pathophysiological mechanisms Here we discuss key working group, its ongoing projects directions for large‐scale, collaborative mental illness.

Language: Английский

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Biological hypotheses, risk factors, and biomarkers of schizophrenia

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2022, Volume and Issue: 120, P. 110626 - 110626

Published: Aug. 31, 2022

Language: Английский

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Integrative omics of schizophrenia: from genetic determinants to clinical classification and risk prediction

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 27(1), P. 113 - 126

Published: June 30, 2021

Language: Английский

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The genetic relationships between brain structure and schizophrenia

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 28, 2023

Abstract Genetic risks for schizophrenia are theoretically mediated by genetic effects on brain structure but it has been unclear which genes associated with both and cortical phenotypes. We accessed genome-wide association studies (GWAS) of ( N = 69,369 cases; 236,642 controls), three magnetic resonance imaging (MRI) metrics (surface area, thickness, neurite density index) measured at 180 areas 36,843, UK Biobank). Using Hi-C-coupled MAGMA, 61 were significantly one or more MRI metrics. Whole genome analysis partial least squares demonstrated significant covariation between area thickness most regions. similarity was strongly coupled to their phenotypic covariance, phenotypes strongest in the hubs structural covariance networks. Pleiotropically enriched neurodevelopmental processes positionally concentrated chromosomes 3p21, 17q21 11p11. Mendelian randomization indicated that genetically determined variation a posterior cingulate could be causal schizophrenia. Parallel analyses GWAS bipolar disorder, Alzheimer’s disease height showed pleiotropic stronger compared other disorders.

Language: Английский

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Statistical Learning Methods for Neuroimaging Data Analysis with Applications

Annual Review of Biomedical Data Science, Journal Year: 2023, Volume and Issue: 6(1), P. 73 - 104

Published: April 26, 2023

The aim of this review is to provide a comprehensive survey statistical challenges in neuroimaging data analysis, from techniques large-scale studies and learning methods. We briefly eight popular their potential applications neuroscience research clinical translation. delineate four themes major image processing analysis methods for at the individual level. neuroimaging-related consortium on imaging genomics discuss population nine population-based associated present recent progress methodology address these challenges.

Language: Английский

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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

Published: July 4, 2019

This review summarizes the last decade of work by ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance over 1,400 scientists across 43 countries, studying human brain in health and disease. Building on large-scale genetic studies that discovered first robustly replicated loci associated with metrics, has diversified into 50 working groups (WGs), pooling worldwide data expertise to answer fundamental questions neuroscience, psychiatry, neurology, genetics. Most WGs focus specific psychiatric neurological conditions, other study normal variation due sex gender differences, or development aging; still develop methodological pipelines tools facilitate harmonized analyses “big data” (i.e., epigenetic data, multimodal MRI, electroencephalography data). These international efforts have yielded largest neuroimaging date schizophrenia, bipolar disorder, major depressive post-traumatic stress substance use disorders, obsessive-compulsive attention-deficit/hyperactivity autism spectrum epilepsy, 22q11.2 deletion syndrome. More recent formed anxiety suicidal thoughts behavior, sleep insomnia, eating irritability, injury, antisocial personality conduct dissociative identity disorder. Here, we summarize ENIGMA’s activities ongoing projects, describe successes challenges encountered along way. We highlight advantages collaborative coordinated for testing reproducibility robustness findings, offering opportunity identify systems involved clinical syndromes diverse samples genetic, environmental, demographic, cognitive psychosocial factors.

Language: Английский

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Inferring cell-type-specific causal gene regulatory networks during human neurogenesis

Genome biology, Journal Year: 2023, Volume and Issue: 24(1)

Published: May 30, 2023

Abstract Background Genetic variation influences both chromatin accessibility, assessed in accessibility quantitative trait loci (caQTL) studies, and gene expression, expression QTL (eQTL) studies. variants can impact either nearby genes (cis-eQTLs) or distal (trans-eQTLs). Colocalization between caQTL eQTL, cis- trans-eQTLs suggests that they share causal variants. However, pairwise colocalization these molecular QTLs does not guarantee a relationship. Mediation analysis be applied to assess the evidence supporting causality versus independence QTLs. Given function of cell-type-specific, we performed mediation analyses find epigenetic regulatory pathways for within two major cell types developing human cortex, progenitors neurons. Results We 168 38 is mediated by neurons, respectively. also 11 12 downstream upstream Moreover, discover genetic locus associated with inter-individual differences brain structure shows SLC26A7 through identifying mechanisms common variant association trait. Conclusions In this study, identify cell-type-specific networks whereby impacts on were expression. Identification paths will enable prioritizing actionable targets perturbing key processes during neurodevelopment.

Language: Английский

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Evaluating brain structure traits as endophenotypes using polygenicity and discoverability

Human Brain Mapping, Journal Year: 2020, Volume and Issue: 43(1), P. 329 - 340

Published: Oct. 24, 2020

Human brain structure traits have been hypothesized to be broad endophenotypes for neuropsychiatric disorders, implying that are comparatively "closer the underlying biology." Genome-wide association studies from large sample sizes allow comparison of common variant genetic architectures between test evidence supporting this claim. Endophenotypes, compared less polygenicity, with greater effect size each susceptible SNP, requiring smaller discover them. Here, we compare polygenicity and discoverability traits, other (91 in total) directly hypothesis. We found reduced (FDR = 0.01) increased 3.68 × 10-9 ) cortical as aggregated estimates multiple disorders. predict ~8 M individuals will required explain full heritability surface area by genome-wide significant SNPs, whereas over 20 depression. In conclusion, our findings consistent satisfying higher power criterion endophenotypes.

Language: Английский

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