2023
Batra, Puneet | Khera, Amit V
Machine learning to assess coronary artery disease status-is it helpful? Journal Article
In: Lancet, vol. 401, no. 10372, pp. 173–175, 2023, ISSN: 1474-547X.
@article{pmid36563697,
title = {Machine learning to assess coronary artery disease status-is it helpful?},
author = {Puneet Batra and Amit V Khera},
doi = {10.1016/S0140-6736(22)02584-3},
issn = {1474-547X},
year = {2023},
date = {2023-01-01},
journal = {Lancet},
volume = {401},
number = {10372},
pages = {173--175},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hodges, Sierra | Guler, Seyhmus | Sacca, Valeria | Vangel, Mark | Orr, Scott | Pace-Schott, Edward | Wen, Ya | Ge, Tian | Kong, Jian
In: Sleep Med, vol. 101, pp. 393–400, 2023, ISSN: 1878-5506.
Abstract | Links | BibTeX | Tags:
@article{pmid36516523,
title = {Associations among acute and chronic musculoskeletal pain, sleep duration, and C-reactive protein (CRP): A cross-sectional study of the UK biobank dataset},
author = {Sierra Hodges and Seyhmus Guler and Valeria Sacca and Mark Vangel and Scott Orr and Edward Pace-Schott and Ya Wen and Tian Ge and Jian Kong},
doi = {10.1016/j.sleep.2022.11.013},
issn = {1878-5506},
year = {2023},
date = {2023-01-01},
journal = {Sleep Med},
volume = {101},
pages = {393--400},
abstract = {Both musculoskeletal pain and sleep disturbances are major health problems worldwide. Literature suggests that the two are reciprocally related and both may be associated with changes in C-reactive protein (CRP) levels. However, the relationships among musculoskeletal pain, sleep duration, and CRP remain unclear. In this cross-sectional study, we investigated the relationship between acute and chronic musculoskeletal pain, sleep, and inflammation using the data from the initial visit of the UK Biobank. 17,642 individuals with chronic musculoskeletal pain, 11,962 individuals with acute musculoskeletal pain, and 29,604 pain-free controls were included in the analysis. In addition, we validated the findings using data from the second visit assessment of the UK Biobank. We found that 1) chronic pain was associated with higher CRP levels compared to both acute pain and the pain-free controls; 2) chronic pain was associated with a lower sleep score (a measurement of sleep patterns), compared to acute pain and the pain-free controls; and acute pain was associated with lower sleep scores compared to the controls; 3) there was a significant negative association between the sleep score and CRP; 4) CRP may partially mediate the association between chronic pain and decreased sleep score. However, the effect size of the mediation was rather small, and the pathophysiological significance remains uncertain. Further validation is needed. These findings were partly replicated in the UK Biobank second visit assessment cohort with a smaller sample size. Our findings, which are based on the large UK Biobank dataset, support the interplay between musculoskeletal pain, sleep patterns, and the potential mediating role of CRP on this reciprocal relationship.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Both musculoskeletal pain and sleep disturbances are major health problems worldwide. Literature suggests that the two are reciprocally related and both may be associated with changes in C-reactive protein (CRP) levels. However, the relationships among musculoskeletal pain, sleep duration, and CRP remain unclear. In this cross-sectional study, we investigated the relationship between acute and chronic musculoskeletal pain, sleep, and inflammation using the data from the initial visit of the UK Biobank. 17,642 individuals with chronic musculoskeletal pain, 11,962 individuals with acute musculoskeletal pain, and 29,604 pain-free controls were included in the analysis. In addition, we validated the findings using data from the second visit assessment of the UK Biobank. We found that 1) chronic pain was associated with higher CRP levels compared to both acute pain and the pain-free controls; 2) chronic pain was associated with a lower sleep score (a measurement of sleep patterns), compared to acute pain and the pain-free controls; and acute pain was associated with lower sleep scores compared to the controls; 3) there was a significant negative association between the sleep score and CRP; 4) CRP may partially mediate the association between chronic pain and decreased sleep score. However, the effect size of the mediation was rather small, and the pathophysiological significance remains uncertain. Further validation is needed. These findings were partly replicated in the UK Biobank second visit assessment cohort with a smaller sample size. Our findings, which are based on the large UK Biobank dataset, support the interplay between musculoskeletal pain, sleep patterns, and the potential mediating role of CRP on this reciprocal relationship.
Rapino, Francesca | Natoli, Ted | Limone, Francesco | O'Connor, Erin | Blank, Jack | Tegtmeyer, Matthew | Chen, William | Norabuena, Erika | Narula, Juhi | Hazelbaker, Dane | Angelini, Gabriella | Barrett, Lindy | O'Neil, Alison | Beattie, Ursula K | Thanos, Jessica M | de Rivera, Heather | Sheridan, Steven D | Perlis, Roy H | McCarroll, Steven A | Stevens, Beth | Subramanian, Aravind | Nehme, Ralda | Rubin, Lee L
Small-molecule screen reveals pathways that regulate C4 secretion in stem cell-derived astrocytes Journal Article
In: Stem Cell Reports, vol. 18, no. 1, pp. 237–253, 2023, ISSN: 2213-6711.
Abstract | Links | BibTeX | Tags:
@article{pmid36563689,
title = {Small-molecule screen reveals pathways that regulate C4 secretion in stem cell-derived astrocytes},
author = {Francesca Rapino and Ted Natoli and Francesco Limone and Erin O'Connor and Jack Blank and Matthew Tegtmeyer and William Chen and Erika Norabuena and Juhi Narula and Dane Hazelbaker and Gabriella Angelini and Lindy Barrett and Alison O'Neil and Ursula K Beattie and Jessica M Thanos and Heather de Rivera and Steven D Sheridan and Roy H Perlis and Steven A McCarroll and Beth Stevens and Aravind Subramanian and Ralda Nehme and Lee L Rubin},
doi = {10.1016/j.stemcr.2022.11.018},
issn = {2213-6711},
year = {2023},
date = {2023-01-01},
journal = {Stem Cell Reports},
volume = {18},
number = {1},
pages = {237--253},
abstract = {In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease. Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia. To design a disease-relevant assay, we first developed a rapid and robust 3D protocol capable of producing large numbers of astrocytes from pluripotent cells. Transcriptional profiling of these astrocytes confirmed the homogeneity of this population of dorsal fetal-like astrocytes. Using a novel ELISA-based small-molecule screen, we identified epigenetic regulators, as well as inhibitors of intracellular signaling pathways, able to modulate C4 secretion from astrocytes. We then built a connectivity map to predict and validate additional key regulatory pathways, including one involving c-Jun-kinase. This work provides a foundation for developing therapies for CNS diseases involving the complement cascade.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease. Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia. To design a disease-relevant assay, we first developed a rapid and robust 3D protocol capable of producing large numbers of astrocytes from pluripotent cells. Transcriptional profiling of these astrocytes confirmed the homogeneity of this population of dorsal fetal-like astrocytes. Using a novel ELISA-based small-molecule screen, we identified epigenetic regulators, as well as inhibitors of intracellular signaling pathways, able to modulate C4 secretion from astrocytes. We then built a connectivity map to predict and validate additional key regulatory pathways, including one involving c-Jun-kinase. This work provides a foundation for developing therapies for CNS diseases involving the complement cascade.
Zekavat, Seyedeh M | Viana-Huete, Vanesa | Matesanz, Nuria | Jorshery, Saman Doroodgar | Zuriaga, María A | Uddin, Md Mesbah | Trinder, Mark | Paruchuri, Kaavya | Zorita, Virginia | Ferrer-Pérez, Alba | Amorós-Pérez, Marta | Kunderfranco, Paolo | Carriero, Roberta | Greco, Carolina M | Aroca-Crevillen, Alejandra | Hidalgo, Andrés | Damrauer, Scott M | Ballantyne, Christie M | Niroula, Abhishek | Gibson, Christopher J | Pirruccello, James | Griffin, Gabriel | Ebert, Benjamin L | Libby, Peter | Fuster, Valentín | Zhao, Hongyu | Ghassemi, Marzyeh | Natarajan, Pradeep | Bick, Alexander G | Fuster, José J | Klarin, Derek
mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease Journal Article
In: Nat Cardiovasc Res, vol. 2, pp. 144–158, 2023, ISSN: 2731-0590.
Abstract | Links | BibTeX | Tags:
@article{pmid36949957,
title = {mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease},
author = {Seyedeh M Zekavat and Vanesa Viana-Huete and Nuria Matesanz and Saman Doroodgar Jorshery and María A Zuriaga and Md Mesbah Uddin and Mark Trinder and Kaavya Paruchuri and Virginia Zorita and Alba Ferrer-Pérez and Marta Amorós-Pérez and Paolo Kunderfranco and Roberta Carriero and Carolina M Greco and Alejandra Aroca-Crevillen and Andrés Hidalgo and Scott M Damrauer and Christie M Ballantyne and Abhishek Niroula and Christopher J Gibson and James Pirruccello and Gabriel Griffin and Benjamin L Ebert and Peter Libby and Valentín Fuster and Hongyu Zhao and Marzyeh Ghassemi and Pradeep Natarajan and Alexander G Bick and José J Fuster and Derek Klarin},
doi = {10.1038/s44161-022-00206-6},
issn = {2731-0590},
year = {2023},
date = {2023-01-01},
journal = {Nat Cardiovasc Res},
volume = {2},
pages = {144--158},
abstract = {Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA Damage Repair (DDR) genes such as and . To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy, and generated atherosclerosis-prone -/- chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13-weeks post-grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries, and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA Damage Repair (DDR) genes such as and . To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy, and generated atherosclerosis-prone -/- chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13-weeks post-grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries, and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.
Yu, Dongmei | Scharf, Jeremiah M
Direct and Indirect Effects in Trio Studies: You Don't Know What You're Missing Journal Article
In: Biol Psychiatry, vol. 93, no. 1, pp. 6–7, 2023, ISSN: 1873-2402.
Abstract | Links | BibTeX | Tags:
@article{pmid36456078,
title = {Direct and Indirect Effects in Trio Studies: You Don't Know What You're Missing},
author = {Dongmei Yu and Jeremiah M Scharf},
doi = {10.1016/j.biopsych.2022.10.004},
issn = {1873-2402},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Biol Psychiatry},
volume = {93},
number = {1},
pages = {6--7},
abstract = {Direct and Indirect Effects in Trio Studies: You Don't Know What You're Missing},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Direct and Indirect Effects in Trio Studies: You Don't Know What You're Missing
Moorthy, Tiahna | Nguyen, Huyen | Chen, Ying | Austin, Jehannine | Smoller, Jordan W | Hercher, Laura | Sabatello, Maya
How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia? Journal Article
In: Am J Med Genet B Neuropsychiatr Genet, vol. 192, no. 7-8, pp. 161–170, 2023, ISSN: 1552-485X.
Abstract | Links | BibTeX | Tags:
@article{pmid37158703,
title = {How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia?},
author = {Tiahna Moorthy and Huyen Nguyen and Ying Chen and Jehannine Austin and Jordan W Smoller and Laura Hercher and Maya Sabatello},
doi = {10.1002/ajmg.b.32939},
issn = {1552-485X},
year = {2023},
date = {2023-01-01},
journal = {Am J Med Genet B Neuropsychiatr Genet},
volume = {192},
number = {7-8},
pages = {161--170},
abstract = {Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0.21, p = 0.0006) although differences were not statistically significant (Wald Chi-square = 3.29, df = 1, p = 0.07). However, only 48.9% of all participants answered all knowledge questions correctly. Many participants (56.5%), especially researchers (42%), indicated having at least occasional conversations about the role of genetics in psychiatric conditions with patients and/or family members. Most participants (62.7%) indicated that PRS are not yet sufficiently robust for assessment of susceptibility to schizophrenia; most significant obstacles were low predictive power and lack of population diversity in available PRS (selected, respectively, by 53.6% and 29.3% of participants). Nevertheless, 89.8% of participants were optimistic about the use of PRS in the next 10 years, suggesting a belief that current shortcomings could be addressed. Our findings inform about the perceptions of psychiatric professionals regarding PRS and the application of PRS in psychiatry.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0.21, p = 0.0006) although differences were not statistically significant (Wald Chi-square = 3.29, df = 1, p = 0.07). However, only 48.9% of all participants answered all knowledge questions correctly. Many participants (56.5%), especially researchers (42%), indicated having at least occasional conversations about the role of genetics in psychiatric conditions with patients and/or family members. Most participants (62.7%) indicated that PRS are not yet sufficiently robust for assessment of susceptibility to schizophrenia; most sig