المؤلفون: Jason Cunha, Melissa V. Chan, Bongani B. Nkambule, Florian Thibord, Amber Lachapelle, Robin E. Pashek, Ramachandran S. Vasan, Jian Rong, Emelia J. Benjamin, Naomi M. Hamburg, Ming-Huei Chen, Gary F. Mitchell, Andrew D. Johnson

المصدر: Platelets, Vol 34, Iss 1 (2023)

مصطلحات موضوعية: aortic diameter, arterial tonometry, epidemiology, platelet, vascular calcification, Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Arterial tonometry and vascular calcification measures are useful in cardiovascular disease (CVD) risk assessment. Prior studies found associations between tonometry measures, arterial calcium, and CVD risk. Activated platelets release angiopoietin-1 and other factors, which may connect vascular structure and platelet function. We analyzed arterial tonometry, platelet function, aortic, thoracic and coronary calcium, and thoracic and abdominal aorta diameters measured in the Framingham Heart Study Gen3/NOS/OMNI-2 cohorts (n = 3,429, 53.7% women, mean age 54.4 years ±9.3). Platelet reactivity in whole blood or platelet-rich plasma was assessed using 5 assays and 7 agonists. We analyzed linear mixed effects models with platelet reactivity phenotypes as outcomes, adjusting for CVD risk factors and family structure. Higher arterial calcium trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity. Characteristic impedance (Zc) and central pulse pressure positively trended with various platelet traits, while pulse wave velocity and Zc negatively trended with collagen, ADP, and epinephrine traits. All results did not pass a stringent multiple test correction threshold (p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/0953-7104Test; https://doaj.org/toc/1369-1635Test

الوصول الحر: https://doaj.org/article/2cc9f209cc8249bc8794e3a9e2ed04d1Test

المؤلفون: Yao Hu, Stephanie A. Bien, Katherine K. Nishimura, Jeffrey Haessler, Chani J. Hodonsky, Antoine R. Baldassari, Heather M. Highland, Zhe Wang, Michael Preuss, Colleen M. Sitlani, Genevieve L. Wojcik, Ran Tao, Mariaelisa Graff, Laura M. Huckins, Quan Sun, Ming-Huei Chen, Abdou Mousas, Paul L. Auer, Guillaume Lettre, the Blood Cell Consortium, Charles Kooperberg

المصدر: BMC Genomics, Vol 22, Iss 1, Pp 1-11 (2021)

مصطلحات موضوعية: GWAS, White blood cells, Platelets, Multi-ethnic, Biotechnology, TP248.13-248.65, Genetics, QH426-470

الوصف: Abstract Background Circulating white blood cell and platelet traits are clinically linked to various disease outcomes and differ across individuals and ancestry groups. Genetic factors play an important role in determining these traits and many loci have been identified. However, most of these findings were identified in populations of European ancestry (EA), with African Americans (AA), Hispanics/Latinos (HL), and other races/ethnicities being severely underrepresented. Results We performed ancestry-combined and ancestry-specific genome-wide association studies (GWAS) for white blood cell and platelet traits in the ancestrally diverse Population Architecture using Genomics and Epidemiology (PAGE) Study, including 16,201 AA, 21,347 HL, and 27,236 EA participants. We identified six novel findings at suggestive significance (P < 5E-8), which need confirmation, and independent signals at six previously established regions at genome-wide significance (P < 2E-9). We confirmed multiple previously reported genome-wide significant variants in the single variant association analysis and multiple genes using PrediXcan. Evaluation of loci reported from a Euro-centric GWAS indicated attenuation of effect estimates in AA and HL compared to EA populations. Conclusions Our results highlighted the potential to identify ancestry-specific and ancestry-agnostic variants in participants with diverse backgrounds and advocate for continued efforts in improving inclusion of racially/ethnically diverse populations in genetic association studies for complex traits.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2164Test

الوصول الحر: https://doaj.org/article/492ab9ab7f354c8e890b3502d9d97085Test

المؤلفون: Ali R. Keramati, Ming-Huei Chen, Benjamin A. T. Rodriguez, Lisa R. Yanek, Arunoday Bhan, Brady J. Gaynor, Kathleen Ryan, Jennifer A. Brody, Xue Zhong, Qiang Wei, NHLBI Trans-Omics for Precision (TOPMed) Consortium, Kai Kammers, Kanika Kanchan, Kruthika Iyer, Madeline H. Kowalski, Achilleas N. Pitsillides, L. Adrienne Cupples, Bingshan Li, Thorsten M. Schlaeger, Alan R. Shuldiner, Jeffrey R. O’Connell, Ingo Ruczinski, Braxton D. Mitchell, Nauder Faraday, Margaret A. Taub, Lewis C. Becker, Joshua P. Lewis, Rasika A. Mathias, Andrew D. Johnson

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021)

مصطلحات موضوعية: Science

الوصف: Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/21f176ab19b541d294b9acdf21deb0aeTest

المؤلفون: Arif Firmansyah, Ming-Huei Chen, I Wayan Ruspendi Junaedi, Mokhammad Arwani, Anang Kistyanto

المصدر: Frontiers in Psychology, Vol 13 (2022)

مصطلحات موضوعية: transformational leadership, knowledge management, learning organization, schools performance, digital era, Psychology, BF1-990

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fpsyg.2022.895341/fullTest; https://doaj.org/toc/1664-1078Test

الوصول الحر: https://doaj.org/article/060383ea4bf6475f9307e30c17aca5c1Test

المؤلفون: Ming-Huei Chen, Achilleas Pitsillides, Qiong Yang

المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Recognizing that family data provide unique advantage of identifying rare risk variants in genetic association studies, many cohorts with related samples have gone through whole genome sequencing in large initiatives such as the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. Analyzing rare variants poses challenges for binary traits in that some genotype categories may have few or no observed events, causing bias and inflation in commonly used methods. Several methods have recently been proposed to better handle rare variants while accounting for family relationship, but their performances have not been thoroughly evaluated together. Here we compare several existing approaches including SAIGE but not limited to related samples using simulations based on the Framingham Heart Study samples and genotype data from Illumina HumanExome BeadChip where rare variants are the majority. We found that logistic regression with likelihood ratio test applied to related samples was the only approach that did not have inflated type I error rates in both single variant test (SVT) and gene-based tests, followed by Firth logistic regression that had inflation in its direction insensitive gene-based test at prevalence 0.01 only, applied to either related or unrelated samples, though theoretically logistic regression and Firth logistic regression do not account for relatedness in samples. SAIGE had inflation in SVT at prevalence 0.1 or lower and the inflation was eliminated with a minor allele count filter of 5. As for power, there was no approach that outperformed others consistently among all single variant tests and gene-based tests.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/72b245b1894a491e9d3931f638fb49acTest

المؤلفون: Florian Thibord, Melissa V. Chan, Ming-Huei Chen, Andrew D. Johnson

المصدر: HGG Advances, Vol 3, Iss 2, Pp 100095- (2022)

مصطلحات موضوعية: COVID-19, genetics, GWAS, trajectory, MUC4, Genetics, QH426-470

الوصف: Host genetic variants influence the susceptibility and severity of several infectious diseases, and the discovery of genetic associations with coronavirus disease 2019 (COVID-19) phenotypes could help to develop new therapeutic strategies to decrease its burden.Between May 2020 and June 2021, we used COVID-19 data released periodically by UK Biobank and performed 65 genome-wide association studies in up to 18 releases of COVID-19 susceptibility (n = 18,481 cases in June 2021), hospitalization (n = 3,260), severe outcomes (n = 1,244), and deaths (n = 1,104), stratified by sex and ancestry.In coherence with previous studies, we observed two independent signals at the chr3p21.31 locus (rs73062389-A, odds ratio [OR], 1.21 (P = 4.26 × 10−15) and rs71325088-C, OR, 1.62 [P = 2.25 × 10−9]) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A; OR, 1.10; P = 3.30 × 10−12), suggesting an increased risk of infection in non-O blood groups carriers. Additional signals at the APOE (associated with severity and death) LRMDA (susceptibility in non-European) and chr2q32.3 (susceptibility in women) loci were also identified, but did not replicate in independent datasets. We then devised an approach to extract variants suggestively associated (P < 10−5), exhibiting an increase in significance over time. When applied to the susceptibility, hospitalization and severity analyses, this approach revealed the known RPL24, DPP9, and MAPT loci, respectively, among hundreds of other signals.These results, freely available on the GRASP portal, provide insights on the genetic mechanisms involved in COVID-19 phenotypes.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666247722000112Test; https://doaj.org/toc/2666-2477Test

الوصول الحر: https://doaj.org/article/df37faaae8334c61896427c62257ac05Test

المؤلفون: Ming-Huei Chen, Lisa R. Yanek, Joshua D. Backman, John D. Eicher, Jennifer E. Huffman, Yoav Ben-Shlomo, Andrew D. Beswick, Laura M. Yerges-Armstrong, Alan R. Shuldiner, Jeffrey R. O’Connell, Rasika A. Mathias, Diane M. Becker, Lewis C. Becker, Joshua P. Lewis, Andrew D. Johnson, Nauder Faraday

المصدر: Platelets, Vol 30, Iss 2, Pp 164-173 (2019)

مصطلحات موضوعية: platelets, platelet aggregation, snp, genetic association, exome, platelet reactivity, Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Previous genome-wide association studies (GWAS) have identified several variants associated with platelet function phenotypes; however, the proportion of variance explained by the identified variants is mostly small. Rare coding variants, particularly those with high potential for impact on protein structure/function, may have substantial impact on phenotype but are difficult to detect by GWAS. The main purpose of this study was to identify low frequency or rare variants associated with platelet function using genotype data from the Illumina HumanExome Bead Chip. Three family-based cohorts of European ancestry, including ~4,000 total subjects, comprised the discovery cohort and two independent cohorts, one of European and one of African American ancestry, were used for replication. Optical aggregometry in platelet-rich plasma was performed in all the discovery cohorts in response to adenosine diphosphate (ADP), epinephrine, and collagen. Meta-analyses were performed using both gene-based and single nucleotide variant association methods. The gene-based meta-analysis identified a significant association (P = 7.13 × 10–7) between rare genetic variants in ANKRD26 and ADP-induced platelet aggregation. One of the ANKRD26 SNVs - rs191015656, encoding a threonine to isoleucine substitution predicted to alter protein structure/function, was replicated in Europeans. Aggregation increases of ~20–50% were observed in heterozygotes in all cohorts. Novel genetic signals in ABCG1 and HCP5 were also associated with platelet aggregation to ADP in meta-analyses, although only results for HCP5 could be replicated. The SNV in HCP5 intersects epigenetic signatures in CD41+ megakaryocytes suggesting a new functional role in platelet biology for HCP5. This is the first study to use gene-based association methods from SNV array genotypes to identify rare variants related to platelet function. The molecular mechanisms and pathophysiological relevance for the identified genetic associations requires further study.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/0953-7104Test; https://doaj.org/toc/1369-1635Test

الوصول الحر: https://doaj.org/article/5aa226b92c0744349f37efaa641d1094Test

المؤلفون: Yao Hu, Stephanie A. Bien, Katherine K. Nishimura, Jeffrey Haessler, Chani J. Hodonsky, Antoine R. Baldassari, Heather M. Highland, Zhe Wang, Michael Preuss, Colleen M. Sitlani, Genevieve L. Wojcik, Ran Tao, Mariaelisa Graff, Laura M. Huckins, Quan Sun, Ming-Huei Chen, Abdou Mousas, Paul L. Auer, Guillaume Lettre, the Blood Cell Consortium, Weihong Tang, Lihong Qi, Bharat Thyagarajan, Steve Buyske, Myriam Fornage, Lucia A. Hindorff, Yun Li, Danyu Lin, Alexander P. Reiner, Kari E. North, Ruth J. F. Loos, Laura M. Raffield, Ulrike Peters, Christy L. Avery, Charles Kooperberg

المصدر: BMC Genomics, Vol 22, Iss 1, Pp 1-2 (2021)

مصطلحات موضوعية: Biotechnology, TP248.13-248.65, Genetics, QH426-470

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2164Test

الوصول الحر: https://doaj.org/article/7a12d213c8dd412db875b5fa8b1209a6Test

المؤلفون: Adrienne Tin, Yong Li, Jennifer A. Brody, Teresa Nutile, Audrey Y. Chu, Jennifer E. Huffman, Qiong Yang, Ming-Huei Chen, Cassianne Robinson-Cohen, Aurélien Macé, Jun Liu, Ayşe Demirkan, Rossella Sorice, Sanaz Sedaghat, Melody Swen, Bing Yu, Sahar Ghasemi, Alexanda Teumer, Peter Vollenweider, Marina Ciullo, Meng Li, André G. Uitterlinden, Robert Kraaij, Najaf Amin, Jeroen van Rooij, Zoltán Kutalik, Abbas Dehghan, Barbara McKnight, Cornelia M. van Duijn, Alanna Morrison, Bruce M. Psaty, Eric Boerwinkle, Caroline S. Fox, Owen M. Woodward, Anna Köttgen

المصدر: Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018)

مصطلحات موضوعية: Science

الوصف: Elevated serum urate levels are a risk factor for gout. Here, Tin et al. perform whole-exome sequencing in 19,517 individuals and detect low-frequency genetic variants in urate transporter genes, SLC22A12 and SLC2A9, associated with serum urate levels and confirm their damaging nature in vitro and in silico.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/180796564ad94848948b76417618b4adTest

المؤلفون: Ming-Huei Chen, Jiaan-Der Wang, Chia-Man Chou, Chieh-Chung Lin

المصدر: Pediatrics and Neonatology, Vol 58, Iss 2, Pp 128-134 (2017)

مصطلحات موضوعية: biliary atresia, bone health, bone mineral density, children, cytokines, Pediatrics, RJ1-570

الوصف: Hepatic osteodystrophy is a common complication in patients with chronic liver disease, however, bone mineral status in patients with biliary atresia has rarely been investigated. Methods: Twenty-nine children with biliary atresia were enrolled in our study and their demographic data, bone mineral density (BMD) of lumbar spine and bilateral femoral neck, and biochemical parameters were measured and analyzed. Results: The majority of our patients had osteopenia or osteoporosis over at least one part of the skeleton although none had jaundice. Instead of T helper 1 cell cytokine, interleukin (IL)-4 had a significant negative correlation with BMD of the right femoral neck (β = −0.251, p = 0.027) and left femoral neck (β = −0.299, p = 0.012) independently by multiple linear regression analysis. Conclusion: We conclude that chronic inflammation with increased expression of IL-4 may be an important factor for compromised bone health in patients with biliary atresia.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1875957216300687Test; https://doaj.org/toc/1875-9572Test

الوصول الحر: https://doaj.org/article/7db309cd5a2f430080846a4b8d3e6efaTest