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

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(6), P. 817 - 829

Published: May 17, 2021

Language: Английский

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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(12), P. 1636 - 1648

Published: Dec. 1, 2021

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted cross-ancestry genome-wide association study (GWAS) including 29,612 patients ALS 122,656 controls, which identified 15 loci. When combined 8,953 individuals whole-genome sequencing (6,538 patients, 2,415 controls) large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated loci were shared multiple traits within the spectrum but distinct enrichment patterns across brain regions cell types. Of environmental lifestyle factors obtained from literature, Mendelian randomization indicated causal role high cholesterol levels. The combination all signals reveals perturbations vesicle-mediated transport autophagy provides evidence cell-autonomous initiation glutamatergic neurons.

Language: Английский

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Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(5), P. 273 - 288

Published: March 29, 2022

Language: Английский

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Leveraging fine-mapping and multipopulation training data to improve cross-population polygenic risk scores

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(4), P. 450 - 458

Published: April 1, 2022

Language: Английский

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

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(2), P. 174 - 184

Published: Jan. 28, 2021

Language: Английский

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Prefrontal cortex, amygdala, and threat processing: implications for PTSD

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 47(1), P. 247 - 259

Published: Sept. 20, 2021

Abstract Posttraumatic stress disorder can be viewed as a of fear dysregulation. An abundance research suggests that the prefrontal cortex is central to processing—that is, how fears are acquired and strategies regulate or diminish responses. The current review covers foundational on threat acquisition extinction in nonhuman animals, healthy humans, patients with posttraumatic disorder, through lens involvement these processes. Research harnessing advances technology further probe role processes, such use optogenetics rodents brain stimulation will highlighted, well other regulation approaches relevant treatment involve cortex, namely cognitive avoidance/active coping. Despite large body translational research, many questions remain unanswered remains difficult treat. We conclude by outlining future directions related processing implications for disorder.

Language: Английский

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Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain

Neuron, Journal Year: 2021, Volume and Issue: 109(19), P. 3088 - 3103.e5

Published: Sept. 27, 2021

Language: Английский

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The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls

Biological Psychiatry, Journal Year: 2019, Volume and Issue: 88(2), P. 169 - 184

Published: Nov. 1, 2019

Language: Английский

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Transcriptomic organization of the human brain in post-traumatic stress disorder

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 24(1), P. 24 - 33

Published: Dec. 21, 2020

Language: Английский

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Gut Microbiota and Psychiatric Disorders: A Two-Sample Mendelian Randomization Study

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Feb. 4, 2022

Evidence supports the observational associations of gut microbiota with a variety psychiatric disorders, but causal nature such remains obscure. Aiming to comprehensively investigate their relationship and identify specific microbe taxa for diseases, we conducted two-sample Mendelian randomization (MR) analysis microbiome 15 diseases. Specifically, genome-wide association study (GWAS) in 18,473 individuals from MiBioGen was used as exposure sample, GWAS diseases outcome samples. One-hundred ninety bacterial six levels were available analysis. At multiple-testing corrected significance level (phylum P < 5.56 × 10-3, class 3.33 order 2.63 family 1.67 genus 4.90 10-4, species 10-3), following eight seven features (one phylum + three classes one species) identified: Prevotellaceae autism spectrum disorder (P = 5.31 10-4), Betaproteobacteria bipolar 1.53 Actinobacteria schizophrenia 1.33 Bacteroidia Bacteroidales Tourette syndrome 2.51 10-3 extroversion 8.22 10-4 1.09 Clostridium innocuum neuroticism 8.92 10-4). Sensitivity showed no evidence reverse causality, pleiotropy, heterogeneity. Our findings offered novel insights into microbiota-mediated development mechanism disorders.

Language: Английский

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