Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics DOI Creative Commons
Thomas P Spargo, Lachlan Gilchrist, Guy P Hunt

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Sept. 12, 2023

Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation within specific regions enables a new strategy identifying pleiotropy. Genomic with significant ‘local’ genetic correlations can be investigated further using state-of-the-art methodologies fine-mapping and variant colocalisation. We explored utility local approach overlaps between candidate neuropsychiatric disorders, Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Parkinson’s disease, schizophrenia. The identified several associations traits, majority which were loci in human leukocyte antigen region. Colocalisation suggested that disease-implicated variants these often differ traits and, one locus, indicated shared causal ALS AD. Our study might play role multiple diseases distinct mechanisms across despite loci. colocalisation protocol designed this has been implemented flexible pipeline produces HTML reports is available at: https://github.com/ThomasPSpargo/COLOC-reporter.

Language: Английский

Transcriptomic risk scores for attention deficit/hyperactivity disorder DOI Creative Commons
Judit Cabana‐Domínguez, Natalia Llonga, Lorena Arribas

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(8), P. 3493 - 3502

Published: Aug. 1, 2023

Abstract Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. We performed transcriptome-wide association study (TWAS) using the latest genome-wide (GWAS) meta-analysis, in 38,691 individuals with ADHD and 186,843 controls, 14 gene-expression reference panels across multiple brain tissues whole blood. Based on TWAS results, we selected subsets of genes constructed transcriptomic risk scores (TRSs) for peripheral blood mononuclear cells controls. found evidence between TRSs expression profiles from areas, carrying higher burden than were uncorrelated polygenic score (PRS) and, combination PRS, improved significantly proportion variance explained over PRS-only model. These results support complementary predictive potential genetic underscore utility gene prediction deeper insight molecular mechanisms underlying ADHD.

Language: Английский

Citations

5
Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics DOI Creative Commons
Thomas P Spargo, Lachlan Gilchrist, Guy P Hunt

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Sept. 12, 2023

Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation within specific regions enables a new strategy identifying pleiotropy. Genomic with significant ‘local’ genetic correlations can be investigated further using state-of-the-art methodologies fine-mapping and variant colocalisation. We explored utility local approach overlaps between candidate neuropsychiatric disorders, Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Parkinson’s disease, schizophrenia. The identified several associations traits, majority which were loci in human leukocyte antigen region. Colocalisation suggested that disease-implicated variants these often differ traits and, one locus, indicated shared causal ALS AD. Our study might play role multiple diseases distinct mechanisms across despite loci. colocalisation protocol designed this has been implemented flexible pipeline produces HTML reports is available at: https://github.com/ThomasPSpargo/COLOC-reporter.

Language: Английский

Citations

1