ArticleAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics2020
TWAS pathway method greatly enhances the number of leads for uncovering the molecular underpinnings of psychiatric disorders.
Article in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Leveraging genomic and transcriptomic data of diverse ancestry to uncover mechanisms of psychiatric risk in the adult and developing brain.Nature communications · 2025Article
- Utilising genomic association data for causal inference in anorexia nervosa.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- GRPa-PRS: A risk stratification method to identify genetically-regulated pathways in polygenic diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Trans-ancestry Genome-Wide Analyses in UK Biobank Yield Novel Risk Loci for Major Depression.medRxiv : the preprint server for health sciences · 2025Article
- The goldmine of GWAS summary statistics: a systematic review of methods and tools.BioData mining · 2024Article
- A transcriptomic atlas of the human brain reveals genetically determined aspects of neuropsychiatric health.American journal of human genetics · 2024Article
- Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.Science (New York, N.Y.) · 2024Article
- Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with alcohol dependence.Research square · 2024Article
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- A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility.NPJ genomic medicine · 2022Article
- Mineralocorticoid receptor and glucocorticoid receptor work alone and together in cell-type-specific manner: Implications for resilience prediction and targeted therapy.Neurobiology of stress · 2022Article
- Hearing loss and tinnitus: association studies for complex-hearing disorders in mouse and man.Human genetics · 2022Review
- Contributions of PTSD polygenic risk and environmental stress to suicidality in preadolescents.Neurobiology of stress · 2021Article
- From genetics to systems biology of stress-related mental disorders.Neurobiology of stress · 2021Article
- Increasing the resolution and precision of psychiatric genome-wide association studies by re-imputing summary statistics using a large, diverse reference panel.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2021Review
- TWAS pathway method greatly enhances the number of leads for uncovering the molecular underpinnings of psychiatric disorders.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2020Article
- Integrative Post-Genome-Wide Association Study Analyses Relevant to Psychiatric Disorders: Imputing Transcriptome and Proteome Signals.Complex psychiatryReview
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12 authors at 6 institutions in 2 countries.
Funding
Abstract
Genetic signal detection in genome-wide association studies (GWAS) is enhanced by pooling small signals from multiple Single Nucleotide Polymorphism (SNP), for example, across genes and pathways. Because genes are believed to influence traits via gene expression, it is of interest to combine information from expression Quantitative Trait Loci (eQTLs) in a gene or genes in the same pathway. Such methods, widely referred to as transcriptomic wide association studies (TWAS), already exist for gene analysis. Due to the possibility of eliminating most of the confounding effects of linkage disequilibrium (LD) from TWAS gene statistics, pathway TWAS methods would be very useful in uncovering the true molecular basis of psychiatric disorders. However, such methods are not yet available for arbitrarily large pathways/gene sets. This is possibly due to the quadratic (as a function of the number of SNPs) computational burden for computing LD across large chromosomal regions. To overcome this obstacle, we propose JEPEGMIX2-P, a novel TWAS pathway method that (a) has a linear computational burden, (b) uses a large and diverse reference panel (33 K subjects), (c) is competitive (adjusts for background enrichment in gene TWAS statistics), and (d) is applicable as-is to ethnically mixed-cohorts. To underline its potential for increasing the power to uncover genetic signals over the commonly used nontranscriptomics methods, for example, MAGMA, we applied JEPEGMIX2-P to summary statistics of most large meta-analyses from Psychiatric Genetics Consortium (PGC). While our work is just the very first step toward clinical translation of psychiatric disorders, PGC anorexia results suggest a possible avenue for treatment.
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