ORCID Profile
0000-0003-3093-0279
Current Organisation
Memorial Sloan Kettering Cancer Center
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2019
DOI: 10.1161/STROKEAHA.119.026089
Abstract: Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical power calculation, inverse-variance weighted MR was performed to pool estimates across different instruments. The Cochran Q heterogeneity test, weighted median MR, and MR pleiotropy residual sum and outlier were used to explore possible bias relating to inclusion of pleiotropic variants. There was no MR evidence for an effect of genetically determined risk of depression on ischemic stroke risk. Although suffering low statistical power, the main inverse-variance weighted MR analysis was suggestive of a detrimental effect of genetically determined risk of depression on functional outcome after ischemic stroke (odds ratio of poor outcome [modified Rankin Scale, ≥3] per 1-SD increase in genetically determined risk of depression, 1.81 95% CI, 0.98–3.35 P =0.06). There was no evidence of heterogeneity between MR estimates produced by different instruments (Q P =0.26). Comparable MR estimates were obtained with weighted median MR (odds ratio, 2.57 95% CI, 1.05–6.25 P =0.04) and MR pleiotropy residual sum and outlier (odds ratio, 1.81 95% CI, 0.95–3.46 P =0.08). We found no MR evidence of genetically determined risk of depression affecting ischemic stroke risk but did find consistent MR evidence suggestive of a possible effect on functional outcome after ischemic stroke. Given the widespread prevalence of depression-related morbidity, these findings could have implications for prognostication and personalized rehabilitation after stroke.
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1105
Publisher: Springer New York
Date: 2015
DOI: 10.1007/978-1-4939-2498-1_17
Abstract: Follicular helper T (Tfh) cells are the helper T-cell subset that localizes in germinal centers within secondary lymphoid organs. They support B cells to produce high-affinity antibodies and generate B-cell memory. By contrast, follicular regulatory T (Tfr) cells localize in germinal centers to suppress B-cell responses. Coordinately regulating antibody responses, Tfh and Tfr cells play a critical role for vaccination, infectious disease control, and the development of autoimmune diseases. Although bona fide Tfh and Tfr cells are hardly detected in human blood, circulating Tfh and Tfr memory cells in blood can be used to investigate their functions in health and disease. We have developed a comprehensive flow cytometric analysis to define different circulating Tfh and Tfr populations within CXCR5(+) CD4(+) T-cell population in human blood, based on numerous cell surface markers including CD25, CD127, CCR7, PD-1, CXCR3, and CCR6.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2022
DOI: 10.1038/S41467-022-28729-3
Abstract: Many in idual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR -p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR -219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte–endothelial cell adhesion and vascular inflammation. We also associate PROCR -219Gly with an increased pro-thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR -219Gly to CAD through anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides a framework to reveal the mechanisms underlying similar cross-phenotype associations.
Publisher: Public Library of Science (PLoS)
Date: 20-06-2019
Location: United States of America
No related grants have been discovered for Zhaohua Hou.