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Denis A. Baird Jimmy Z. Liu Jie Zheng Solveig K. Sieberts Thanneer Perumal Benjamin Elsworth Tom G. Richardson Chia-Yen Chen Minerva M. Carrasquillo Mariet Allen Joseph S. Reddy Philip L. De Jager Nilufer Ertekin-Taner Lara M. Mangravite Ben Logsdon Karol Estrada Philip C. Haycock Gibran Hemani Heiko Runz George Davey Smith Tom R. Gaunt AMP-AD eQTL working group 《PLoS genetics》2021,17(1)
Discovering drugs that efficiently treat brain diseases has been challenging. Genetic variants that modulate the expression of potential drug targets can be utilized to assess the efficacy of therapeutic interventions. We therefore employed Mendelian Randomization (MR) on gene expression measured in brain tissue to identify drug targets involved in neurological and psychiatric diseases. We conducted a two-sample MR using cis-acting brain-derived expression quantitative trait loci (eQTLs) from the Accelerating Medicines Partnership for Alzheimer’s Disease consortium (AMP-AD) and the CommonMind Consortium (CMC) meta-analysis study (n = 1,286) as genetic instruments to predict the effects of 7,137 genes on 12 neurological and psychiatric disorders. We conducted Bayesian colocalization analysis on the top MR findings (using P<6x10-7 as evidence threshold, Bonferroni-corrected for 80,557 MR tests) to confirm sharing of the same causal variants between gene expression and trait in each genomic region. We then intersected the colocalized genes with known monogenic disease genes recorded in Online Mendelian Inheritance in Man (OMIM) and with genes annotated as drug targets in the Open Targets platform to identify promising drug targets. 80 eQTLs showed MR evidence of a causal effect, from which we prioritised 47 genes based on colocalization with the trait. We causally linked the expression of 23 genes with schizophrenia and a single gene each with anorexia, bipolar disorder and major depressive disorder within the psychiatric diseases and 9 genes with Alzheimer’s disease, 6 genes with Parkinson’s disease, 4 genes with multiple sclerosis and two genes with amyotrophic lateral sclerosis within the neurological diseases we tested. From these we identified five genes (ACE, GPNMB, KCNQ5, RERE and SUOX) as attractive drug targets that may warrant follow-up in functional studies and clinical trials, demonstrating the value of this study design for discovering drug targets in neuropsychiatric diseases. 相似文献
623.
Peijun Gong Qingyun Li Qiang Wang Karol Karnowski David D. Sampson 《Journal of biophotonics》2020,13(9)
We show that polarization‐sensitive optical coherence tomography angiography (PS‐OCTA) based on full Jones matrix assessment of speckle decorrelation offers improved contrast and depth of vessel imaging over conventional OCTA. We determine how best to combine the individual Jones matrix elements and compare the resulting image quality to that of a conventional OCT scanner by co‐locating and imaging the same skin locations with closely matched scanning setups. Vessel projection images from finger and forearm skin demonstrate the benefits of Jones matrix‐based PS‐OCTA. Our study provides a promising starting point and a useful reference for future pre‐clinical and clinical applications of Jones matrix‐based PS‐OCTA. 相似文献
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Asteropeia andPhysena are both enigmatic woody dicotyledons from Madagascar. Various taxonomic affinities have been suggested for both genera, but no consensus has been reached. An analysis of rbcL sequence data strongly supports recognition of the sister-group relationship ofAsteropeia andPhysena and their placement as the sister group to Caryophyllales. Many similarities were noted betweenAsteropeia andPhysena for stem, wood, leaf, flower, pollen, and fruit characters. The most notable differences are found in the morphology of the flowers and the anatomy of the wood rays. 相似文献
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Ranglová Karolína Bureš Michal Manoel João Câmara Lakatos Gergely Ernő Masojídek Jiří 《Journal of applied phycology》2022,34(1):31-41
Journal of Applied Phycology - In this study, we aimed to set up and test two models of annular-column photobioreactors (AC-PBR 1 and AC-PBR 2) in order to produce microalgae for fish hatcheries.... 相似文献
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