Multi-omics QTL papers

With emphasize on brain and neurodegenerative disorder applications

  1. Single-cell genomics and regulatory networks for 388 human brains
    • Science, 2024
    • Summary: This study utilized single-cell RNA sequencing to analyze 388 human brains, providing a comprehensive atlas of cell-type-specific gene expression. The research identified how genetic variants influence gene expression across various brain cell types, offering insights into the regulatory networks that underpin brain function and disease.
  2. Global impact of unproductive splicing on human gene expression
    • Nature Genetics, 2024
    • Summary: This research investigates the prevalence and impact of unproductive splicing events on gene expression in humans, revealing that such events are widespread and can significantly influence gene regulation.
  3. Single-Nucleus Atlas of Cell-Type Specific Genetic Regulation in the Human Prefrontal Cortex
    • medRxiv, 2024
    • Summary: This preprint presents a high-resolution atlas of genetic regulation in the human prefrontal cortex, derived from single-nucleus RNA sequencing of 1,384 donors. The study identifies cell-type-specific regulatory effects and highlights genes implicated in neuropsychiatric and neurodegenerative diseases.
  4. Cell state-dependent allelic effects and contextual Mendelian randomization in the human brain
    • Nature Genetics, 2024
    • Summary: This research explores how allelic effects on gene expression vary depending on cell state, emphasizing the dynamic nature of genetic regulation in the brain. The findings have implications for understanding the context-specific roles of genetic variants in brain disorders.
  5. Cell-subtype specific effects of genetic variation in the aging and Alzheimer’s disease human brain
    • Nature Genetics, 2024
    • Summary: This study generated single-nucleus RNA sequencing data from the neocortex of 424 individuals of advanced age to assess the effect of genetic variants on RNA expression in cis (cis-expression quantitative trait loci) across various cell types and subtypes. The findings provide insights into cell-type-specific genetic regulation in the context of aging and Alzheimer’s disease.
  6. Single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease
  7. Integrated multimodal cell atlas of Alzheimer’s disease
    • Nature Neuroscience, 2024
    • Summary: Researchers employed multi-omics, spatial genomics, and reference atlases from the BRAIN Initiative to study cell types in the middle temporal gyrus of 84 donors with varying AD pathology. This comprehensive atlas provides insights into cell-type-specific changes associated with AD.
  8. Single-cell multiregion dissection of Alzheimer’s disease
    • Nature, 2024
    • Summary: This study presented a single-cell transcriptomic atlas covering six different brain regions from 283 post-mortem human brains. The extensive dataset offers valuable information on regional and cell-type-specific alterations in AD.
  9. Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease
  10. Molecular cascades and cell type–specific signatures in ASD revealed by single-cell genomics
  11. Transcriptomic diversity of cell types across the adult human brain
    • Science, 2023
    • Summary: This study presents a comprehensive single-cell transcriptome atlas of the adult human brain, revealing cell-type-specific gene expression patterns. The data serve as a valuable resource for understanding brain function and disease.
  12. Integrative single-nucleus multi-omics analysis prioritizes candidate genes for Alzheimer’s disease
    • Cell & Bioscience, 2023
    • Summary: By integrating single-nucleus RNA sequencing with other omics data, this study identifies candidate genes associated with Alzheimer’s disease. The approach highlights the power of multi-omics in uncovering the molecular underpinnings of neurodegenerative diseases.
  13. A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank
  14. Plasma proteomic associations with genetics and health in the UK Biobank
    • Nature, 2023
    • Summary: This research characterizes the genetic architecture of the plasma proteome using data from the UK Biobank. It identifies protein quantitative trait loci (pQTLs) and offers insights into the genetic regulation of protein levels in the blood.
  15. Brain expression quantitative trait locus and network analyses reveal downstream effects and putative drivers for brain-related diseases
    • Nature Genetics, 2023
    • Summary: This study utilized the MetaBrain resource, harmonizing 8,613 RNA-sequencing samples from 14 brain datasets to perform cis- and trans-expression QTL meta-analyses. The research identified tissue-dependent cis-eQTLs and employed brain-specific gene-co-regulation networks to link GWAS loci, prioritizing additional genes associated with central nervous system diseases, including Alzheimer’s disease.
  16. Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration
  17. Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer’s disease pathology
  18. Epigenomic dissection of Alzheimer’s disease pinpoints causal variants and reveals epigenome erosion
  19. Single-nucleus multiregion transcriptomic analysis of brain vasculature in Alzheimer’s disease
  20. European and African-specific plasma protein-QTL and metabolite-QTL analyses identify ancestry-specific T2D effector proteins and metabolites
  21. Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies
  22. Cell-type-specific cis-eQTLs in eight human brain cell types identify novel risk genes for psychiatric and neurological disorders
  23. Genetics of the human microglia regulome refines Alzheimer’s disease risk loci
  24. Single-cell eQTL mapping identifies cell type–specific genetic control of autoimmune disease
  25. CSF proteome profiling identifies biomarkers for Alzheimer’s disease progression
    • Nature Aging, 2022
    • Summary: This research profiles the cerebrospinal fluid proteome to identify biomarkers associated with Alzheimer’s disease progression. The study provides insights into disease mechanisms and potential targets for intervention.
  26. New insights into the genetic etiology of Alzheimer’s disease and related dementias
    • Nature Genetics, 2022
    • Summary: This research mapped expression QTLs (eQTLs) and splicing QTLs (sQTLs) in AD-relevant brain regions, uncovering genetic variants that modulate gene expression and splicing linked to AD risk. The findings enhance our comprehension of the genetic architecture underlying AD and related dementias.
  27. Multi-ancestry eQTL meta-analysis of human brain identifies candidate causal variants for brain-related traits
  28. Large-scale integration of the plasma proteome with genetics and disease
  29. Integration of Alzheimer’s disease genetics and myeloid genomics identifies disease risk regulatory elements and genes
  30. The impact of cell type and context-dependent regulatory variants on human immune traits
    • Genome Biology, 2021
    • Summary: This study performs a comprehensive characterization of the putative mechanisms by which GWAS loci impact human immune traits, emphasizing the importance of cell type and context-dependent regulatory variants.
  31. Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level
    • Nature Neuroscience, 2021
    • Summary: This comprehensive analysis integrated proteomic and transcriptomic data from Alzheimer’s disease brains, uncovering significant proteomic alterations that were not evident at the RNA level. The findings highlight the importance of multi-layered molecular analyses in understanding AD pathology.
  32. Cell-type-specific expression quantitative trait loci associated with Alzheimer disease in blood and brain tissue
    • Translational Psychiatry, 2021
    • Summary: This research investigated AD-related gene expression patterns in specific brain cell types, identifying cell-type-specific eQTLs associated with Alzheimer’s disease. The study emphasizes the significance of considering cellular context when examining genetic regulation in AD.
  33. Cell type-specific genetic regulation of gene expression across the human brain
    • Science, 2020
    • Summary: This study illustrates how genetic variants that operate in a cell type–specific manner affect gene regulation and can be linked to complex traits.
  34. Regional Variation of Splicing QTLs in Human Brain
    • The American Journal of Human Genetics, 2020
    • Summary: This research systematically discovered sQTLs in 13 regions of the human brain using RNA sequencing data from the Genotype-Tissue Expression (GTEx) project. The study identified both regionally ubiquitous and regionally specific sQTLs, providing insights into the genetic regulation of alternative splicing in the brain.
  35. An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease
    • Nature Genetics, 2020
    • Summary: This study integrated transcriptomic, proteomic, and epigenomic analyses of postmortem human brains to identify molecular pathways involved in AD. The findings revealed significant epigenetic modifications contributing to disease progression.
  36. Single-cell transcriptomic analysis of Alzheimer’s disease
    • Nature, 2019
    • Summary: This pioneering study conducted single-cell RNA sequencing on postmortem human brains, identifying cell-type-specific gene expression changes associated with AD. The research highlighted the involvement of microglia and oligodendrocyte precursor cells in AD pathology.
  37. Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease
    • Nature, 2015
    • Summary: This study mapped epigenomic changes in mouse models and human brains affected by AD, revealing that immune cell activation and inflammation are early events in disease progression, preceding neuronal loss.
  38. The GTEx Consortium atlas of genetic regulatory effects across human tissues
  39. An xQTL map integrates the genetic architecture of the human brain’s transcriptome and epigenome
  40. A compendium of uniformly processed human gene expression and splicing quantitative trait loci
    • Nature Genetics, 2021
    • Summary: This paper introduces the eQTL Catalogue, an open database of uniformly processed human molecular quantitative trait loci, enhancing the interpretation of genetic associations with complex traits.
  41. Genetic control of expression and splicing in developing human brain informs disease mechanisms
    • Cell, 2019
    • Summary: This study explores how genetic variants influence gene expression and splicing during human brain development. The findings provide insights into the molecular mechanisms underlying neurodevelopmental disorders and highlight potential therapeutic targets.
  42. Comprehensive functional genomic resource and integrative model for the human brain
  43. Genetic atlas of the human plasma proteome
    • Nature, 2018
    • Summary: This comprehensive analysis maps the genetic determinants of protein levels in human plasma, identifying numerous pQTLs. The study enhances our understanding of the genetic regulation of the proteome and its relevance to disease.
  44. Fine-mapping inflammatory bowel disease loci to single variant resolution
    • Nature, 2017
    • This is Hailiang’s fine-mapping paper, shown here to also inform some good ideas how we draft the QTL fine-mapping papers.