FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3097552816> ?p ?o ?g. }

• W3097552816 abstract "Microglia are tissue-resident macrophages of the central nervous system that are essential for homeostasis, immune response, neurogenesis, and neuronal plasticity. Genetic studies have strongly implicated microglial dysfunction in multiple neurodegenerative diseases. However, investigating genetically-driven changes in gene expression in microglia has been limited by lack of access to these cells from the number of subjects required to perform well-powered genomic analysis.Here we describe the transcriptome analysis of 255 primary human CD11b+ microglia samples isolated at autopsy from multiple brain regions of 100 human subjects with neurodegenerative and neuropsychiatric disorders. We performed systematic analyses to investigate various aspects of microglial heterogeneities including brain region, age, sex, and disease. By intersecting transcriptomics and genetics, we performed expression and splicing QTL analyses and by combining microglia from four different brain regions using a multivariate meta-analysis method (mashR).We observed widespread transcriptome variation associated with microglia, suggesting that these genes may play important role in diversified responses to pathological stimuli of microglia at different locations. We also observed 1,693 genes (FDR < 0.05) whose expression is associated with age including many genes in Alzheimer's (AD) (MS4A6A, FCER1G, and CR1) or Parkinson's disease (PD) (BST1 and FCGR2A) GWAS loci. We identified 3,611 eQTLs (mashR local false sign rate < 0.05), of which 50% (1,791) show region-specific effects. We identified over 300 eQTLs that colocalize with a known risk locus for a neurodegenerative or neuropsychiatric disease, nearly half of which are not found in prefrontal cortex or in peripheral monocytes. We prioritized 7 and 13 putative causal genes for AD and PD, respectively, many of which are novel genes (ITGAX, USP6NL, TSPOAP1, P2RY12, FCGR2C, and FGF20). Fine-mapping of these colocalized loci with CNS chromatin accessibility (ATAC-seq) and histone modification (H3K27ac) data nominates candidate causal variants that are within microglia-specific enhancers and are likely to modify disease susceptibility by regulating gene expression and/or splicing in microglia.In summary, we have built the most comprehensive catalog to date of genetic effects on the microglia transcriptome and propose molecular mechanisms of action of candidate functional variants in several neurological and neuropsychiatric diseases." @default.
• W3097552816 created "2020-11-09" @default.
• W3097552816 creator A5001322329 @default.
• W3097552816 creator A5020239526 @default.
• W3097552816 creator A5021955803 @default.
• W3097552816 creator A5025456226 @default.
• W3097552816 creator A5029055395 @default.
• W3097552816 creator A5029264773 @default.
• W3097552816 creator A5031245590 @default.
• W3097552816 creator A5033994530 @default.
• W3097552816 creator A5038805271 @default.
• W3097552816 creator A5045132350 @default.
• W3097552816 creator A5055109212 @default.
• W3097552816 creator A5055272171 @default.
• W3097552816 creator A5057482421 @default.
• W3097552816 creator A5063418910 @default.
• W3097552816 creator A5066447047 @default.
• W3097552816 creator A5076119143 @default.
• W3097552816 creator A5077512311 @default.
• W3097552816 creator A5090829178 @default.
• W3097552816 creator A5091014525 @default.
• W3097552816 date "2021-12-01" @default.
• W3097552816 modified "2023-10-18" @default.
• W3097552816 title "Atlas of genetic effects in human microglia transcriptome across brain regions, aging and disease pathologies" @default.
• W3097552816 cites W175813982 @default.
• W3097552816 cites W1973756832 @default.
• W3097552816 cites W1976428955 @default.
• W3097552816 cites W1986911601 @default.
• W3097552816 cites W1999574084 @default.
• W3097552816 cites W2009178411 @default.
• W3097552816 cites W2012697072 @default.
• W3097552816 cites W2026114862 @default.
• W3097552816 cites W2033105784 @default.
• W3097552816 cites W2042421957 @default.
• W3097552816 cites W2053646585 @default.
• W3097552816 cites W2064257734 @default.
• W3097552816 cites W2064782801 @default.
• W3097552816 cites W2066957293 @default.
• W3097552816 cites W2072420737 @default.
• W3097552816 cites W2073836327 @default.
• W3097552816 cites W2096327192 @default.
• W3097552816 cites W2099085143 @default.
• W3097552816 cites W2101280135 @default.
• W3097552816 cites W2101357408 @default.
• W3097552816 cites W2102213696 @default.
• W3097552816 cites W2104549677 @default.
• W3097552816 cites W2106578986 @default.
• W3097552816 cites W2108532908 @default.
• W3097552816 cites W2109759840 @default.
• W3097552816 cites W2114104545 @default.
• W3097552816 cites W2115779804 @default.
• W3097552816 cites W2123446167 @default.
• W3097552816 cites W2124954099 @default.
• W3097552816 cites W2125905177 @default.
• W3097552816 cites W2131686384 @default.
• W3097552816 cites W2137526110 @default.
• W3097552816 cites W2142386149 @default.
• W3097552816 cites W2155449815 @default.
• W3097552816 cites W2161428211 @default.
• W3097552816 cites W2169456326 @default.
• W3097552816 cites W2170706621 @default.
• W3097552816 cites W2173367702 @default.
• W3097552816 cites W2179438025 @default.
• W3097552816 cites W2261364877 @default.
• W3097552816 cites W2297334215 @default.
• W3097552816 cites W2336518991 @default.
• W3097552816 cites W2344561059 @default.
• W3097552816 cites W2415131480 @default.
• W3097552816 cites W2499242515 @default.
• W3097552816 cites W2510973425 @default.
• W3097552816 cites W2526546796 @default.
• W3097552816 cites W2529241974 @default.
• W3097552816 cites W2554948325 @default.
• W3097552816 cites W2560048039 @default.
• W3097552816 cites W2560760305 @default.
• W3097552816 cites W2568020671 @default.
• W3097552816 cites W2586076302 @default.
• W3097552816 cites W2619332462 @default.
• W3097552816 cites W2622807556 @default.
• W3097552816 cites W2634812549 @default.
• W3097552816 cites W2725043130 @default.
• W3097552816 cites W2729351500 @default.
• W3097552816 cites W2765193380 @default.
• W3097552816 cites W2771554318 @default.
• W3097552816 cites W2774883395 @default.
• W3097552816 cites W2787933178 @default.
• W3097552816 cites W2793657534 @default.
• W3097552816 cites W2795435173 @default.
• W3097552816 cites W2890998227 @default.
• W3097552816 cites W2893655504 @default.
• W3097552816 cites W2894831642 @default.
• W3097552816 cites W2900596992 @default.
• W3097552816 cites W2901838561 @default.
• W3097552816 cites W2905335418 @default.
• W3097552816 cites W2908002252 @default.
• W3097552816 cites W2914756534 @default.
• W3097552816 cites W2916749909 @default.
• W3097552816 cites W2921234203 @default.
• W3097552816 cites W2924181660 @default.
• W3097552816 cites W2942678593 @default.

• next