Medicine and Health Sciences Commons^™

Traf3-Ewsr1 Signaling Axis Acts As A Checkpoint On Germinal Center Responses, Yanchuan Li, Lele Zhu, Chun-Jung Ko, Jin-Young Yang, Hongjiao Wang, Ganiraju Manyam, Jing Wang, Xuhong Cheng, Shuli Zhao, Zuliang Jie

Faculty, Staff and Student Publications

The formation of germinal centers (GCs) is crucial for humoral immunity and vaccine efficacy. Constant stimulation through microbiota drives the formation of constitutive GCs in Peyer's patches (PPs), which generate B cells that produce antibodies against gut antigens derived from commensal bacteria and infectious pathogens. However, the molecular mechanism that regulates this persistent process is poorly understood. We report that Ewing Sarcoma Breakpoint Region 1 (EWSR1) is a brake to constitutive GC generation and immunoglobulin G (IgG) production in PPs, vaccination-induced GC formation, and IgG responses. Mechanistically, EWSR1 suppresses Bcl6 upregulation after antigen encounter, thereby negatively regulating induced GC B …

Quercetin As An Anticancer Candidate For Glioblastoma Multiforme By Targeting Akt1, Mmp9, Abcb1, And Vegfa: An In Silico Study, Muhammad Hermawan Widyananda, Setyaki Kevin Pratama, Arif Nur Muhammad Ansori, Yulanda Antonius, Viol Dhea Kharisma, Ahmad Affan Ali Murtadlo, Vikash Jakhmola, Maksim Rebezov, Mars Khayrullin, Marina Derkho, Emdad Ullah, Raden Joko Kuncoroningrat Susilo, Suhailah Hayaza, Alexander Patera Nugraha, Annise Proboningrat, Amaq Fadholly, Mada Triandala Sibero, Rahadian Zainul

Karbala International Journal of Modern Science

Quercetin, a natural compound present in various fruits and vegetables, shows promise as a potential inhibitor for glioblastoma multiforme (GBM) development. This study aims to examine the anti-GBM potential of Quercetin. The protein target of Quercetin is identified and analyzed using databases such as NCBI, SEA, CTD, and STRING. Protein-protein interaction (PPI) and functional annotation are carried out based on the obtained target proteins. Molecular docking and dynamics simulations are employed using AutoDock Vina and WebGro tools to analyze the interaction between Quercetin and its target proteins. The prediction of protein targets reveals that Quercetin directly targets four proteins associated …

Examination Of Fully Automated Mammographic Density Measures Using Libra And Breast Cancer Risk In A Cohort Of 21,000 Non-Hispanic White Women, Laurel A Habel, Stacey E Alexeeff, Ninah Achacoso, Vignesh A Arasu, Aimilia Gastounioti, Lawrence Gerstley, Robert J Klein, Rhea Y Liang, Jafi A Lipson, Walter Mankowski, Laurie R Margolies, Joseph H Rothstein, Daniel L Rubin, Li Shen, Adriana Sistig, Xiaoyu Song, Marvella A Villaseñor, Mark Westley, Alice S Whittemore, Martin J Yaffe, Pei Wang, Despina Kontos, Weiva Sieh

Faculty, Staff and Student Publications

BACKGROUND: Breast density is strongly associated with breast cancer risk. Fully automated quantitative density assessment methods have recently been developed that could facilitate large-scale studies, although data on associations with long-term breast cancer risk are limited. We examined LIBRA assessments and breast cancer risk and compared results to prior assessments using Cumulus, an established computer-assisted method requiring manual thresholding.

METHODS: We conducted a cohort study among 21,150 non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were 40-74 years at enrollment, followed for up to 10 years, and had archived …

Gsk-J4 Inhibition Of Kdm6b Histone Demethylase Blocks Adhesion Of Mantle Cell Lymphoma Cells To Stromal Cells By Modulating Nf-Κb Signaling, Laia Sadeghi, Anthony P H Wright

Faculty, Staff and Student Publications

Multiple signaling pathways facilitate the survival and drug resistance of malignant B-cells by regulating their migration and adhesion to microenvironmental niches. NF-κB pathways are commonly dysregulated in mantle cell lymphoma (MCL), but the exact underlying mechanisms are not well understood. Here, using a co-culture model system, we show that the adhesion of MCL cells to stromal cells is associated with elevated levels of KDM6B histone demethylase mRNA in adherent cells. The inhibition of KDM6B activity, using either a selective inhibitor (GSK-J4) or siRNA-mediated knockdown, reduces MCL adhesion to stromal cells. We showed that KDM6B is required both for the removal …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

Ex Vivo Drug Sensitivity Imaging-Based Platform For Primary Acute Lymphoblastic Leukemia Cells, Lauren Rowland, Brandon Smart, Anthony Brown, Gino M Dettorre, Yoshihiro Gocho, Jeremy Hunt, Wenjian Yang, Satoshi Yoshimura, Noemi Reyes, Guoqing Du, August John, Dylan Maxwell, Wendy Stock, Steven Kornblau, Mary V Relling, Hiroto Inaba, Ching-Hon Pui, Jean-Pierre Bourquin, Seth E Karol, Charles G Mullighan, William E Evans, Jun J Yang, Kristine R Crews

Faculty, Staff and Student Publications

Resistance of acute lymphoblastic leukemia (ALL) cells to chemotherapy, whether present at diagnosis or acquired during treatment, is a major cause of treatment failure. Primary ALL cells are accessible for drug sensitivity testing at the time of new diagnosis or at relapse, but there are major limitations with current methods for determining drug sensitivity ex vivo. Here, we describe a functional precision medicine method using a fluorescence imaging platform to test drug sensitivity profiles of primary ALL cells. Leukemia cells are co-cultured with mesenchymal stromal cells and tested with a panel of 40 anti-leukemia drugs to determine individual patterns of …

Proteomic Profiling Across Breast Cancer Cell Lines And Models, Marian Kalocsay, Matthew J Berberich, Robert A Everley, Maulik K Nariya, Mirra Chung, Benjamin Gaudio, Chiara Victor, Gary A Bradshaw, Robyn J Eisert, Marc Hafner, Peter K Sorger, Caitlin E Mills, Kartik Subramanian

Faculty, Staff and Student Publications

We performed quantitative proteomics on 60 human-derived breast cancer cell line models to a depth of ~13,000 proteins. The resulting high-throughput datasets were assessed for quality and reproducibility. We used the datasets to identify and characterize the subtypes of breast cancer and showed that they conform to known transcriptional subtypes, revealing that molecular subtypes are preserved even in under-sampled protein feature sets. All datasets are freely available as public resources on the LINCS portal. We anticipate that these datasets, either in isolation or in combination with complimentary measurements such as genomics, transcriptomics and phosphoproteomics, can be mined for the purpose …

Spatial Transcriptomics Of Intraductal Papillary Mucinous Neoplasms Of The Pancreas Identifies Nkx6-2 As A Driver Of Gastric Differentiation And Indolent Biological Potential, Marta Sans, Yuki Makino, Jimin Min, Kimal I Rajapakshe, Michele Yip-Schneider, C Max Schmidt, Mark W Hurd, Jared K Burks, Javier A Gomez, Fredrik I Thege, Johannes F Fahrmann, Robert A Wolff, Michael P Kim, Paola A Guerrero, Anirban Maitra

Faculty, Staff and Student Publications

Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The most common subtype of IPMNs harbor a gastric foveolar-type epithelium, and these low-grade mucinous neoplasms are harbingers of IPMNs with high-grade dysplasia and cancer. The molecular underpinning of gastric differentiation in IPMNs is unknown, although identifying drivers of this indolent phenotype might enable opportunities for intercepting progression to high-grade IPMN and cancer. We conducted spatial transcriptomics on a cohort of IPMNs, followed by orthogonal and cross species validation studies, which established the transcription factor NKX6-2 as a key determinant of gastric …

The At-Hook Is An Evolutionarily Conserved Auto-Regulatory Domain Of Swi/Snf Required For Cell Lineage Priming, Dhurjhoti Saha, Solomon Hailu, Arjan Hada, Junwoo Lee, Jie Luo, Jeff A Ranish, Yuan-Chi Lin, Kyle Feola, Jim Persinger, Abhinav Jain, Bin Liu, Yue Lu, Payel Sen, Blaine Bartholomew

Faculty, Staff and Student Publications

The SWI/SNF ATP-dependent chromatin remodeler is a master regulator of the epigenome, controlling pluripotency and differentiation. Towards the C-terminus of the catalytic subunit of SWI/SNF is a motif called the AT-hook that is evolutionary conserved. The AT-hook is present in many chromatin modifiers and generally thought to help anchor them to DNA. We observe however that the AT-hook regulates the intrinsic DNA-stimulated ATPase activity aside from promoting SWI/SNF recruitment to DNA or nucleosomes by increasing the reaction velocity a factor of 13 with no accompanying change in substrate affinity (K

Multiomics Analyses Reveal Dars1-As1/Ybx1-Controlled Posttranscriptional Circuits Promoting Glioblastoma Tumorigenesis/Radioresistance, Caishang Zheng, Yanjun Wei, Qiang Zhang, Ming Sun, Yunfei Wang, Jiakai Hou, Peng Zhang, Xiangdong Lv, Dan Su, Yujie Jiang, Joy Gumin, Nidhi Sahni, Baoli Hu, Wenyi Wang, Xi Chen, Daniel J Mcgrail, Chaolin Zhang, Suyun Huang, Han Xu, Junjie Chen, Frederick F Lang, Jian Hu, Yiwen Chen

Faculty, Staff and Student Publications

The glioblastoma (GBM) stem cell-like cells (GSCs) are critical for tumorigenesis/therapeutic resistance of GBM. Mounting evidence supports tumor-promoting function of long noncoding RNAs (lncRNAs), but their role in GSCs remains poorly understood. By combining CRISPRi screen with orthogonal multiomics approaches, we identified a lncRNA DARS1-AS1-controlled posttranscriptional circuitry that promoted the malignant properties of GBM cells/GSCs. Depleting DARS1-AS1 inhibited the proliferation of GBM cells/GSCs and self-renewal of GSCs, prolonging survival in orthotopic GBM models. DARS1-AS1 depletion also impaired the homologous recombination (HR)-mediated double-strand break (DSB) repair and enhanced the radiosensitivity of GBM cells/GSCs. Mechanistically, DARS1-AS1 interacted with YBX1 to promote …

Combined Crispri And Proteomics Screening Reveal A Cohesin-Ctcf-Bound Allele Contributing To Increased Expression Of Ruvbl1 And Prostate Cancer Progression, Yijun Tian, Dandan Dong, Zixian Wang, Lang Wu, Jong Y Park, Gong-Hong Wei, Liang Wang

Faculty, Staff and Student Publications

Genome-wide association studies along with expression quantitative trait locus (eQTL) mapping have identified hundreds of single-nucleotide polymorphisms (SNPs) and their target genes in prostate cancer (PCa), yet functional characterization of these risk loci remains challenging. To screen for potential regulatory SNPs, we designed a CRISPRi library containing 9,133 guide RNAs (gRNAs) to cover 2,166 candidate SNP loci implicated in PCa and identified 117 SNPs that could regulate 90 genes for PCa cell growth advantage. Among these, rs60464856 was covered by multiple gRNAs significantly depleted in screening (FDR < 0.05). Pooled SNP association analysis in the PRACTICAL and FinnGen cohorts showed significantly higher PCa risk for the rs60464856 G allele (p value = 1.2 × 10

Novel Murine Glioblastoma Models That Reflect The Immunotherapy Resistance Profile Of A Human Disease, Chao-Hsien Chen, Renee L Chin, Genevieve P Hartley, Spencer T Lea, Brian J Engel, Cheng-En Hsieh, Rishika Prasad, Jason Roszik, Takashi Shingu, Gregory A Lizee, Amy B Heimberger, Steven W Millward, Jian Hu, David S Hong, Michael A Curran

Faculty, Staff and Student Publications

BACKGROUND: The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We, therefore, developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and their underlying mechanisms.

METHODS: The differential responsiveness of QPP lines was assessed in the brain and flank in untreated, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on the responsiveness of each tumor was measured through …

Facs-Based Genome-Wide Crispr Screens Define Key Regulators Of Dna Damage Signaling Pathways, Min Huang, Fuwen Yao, Litong Nie, Chao Wang, Dan Su, Huimin Zhang, Siting Li, Mengfan Tang, Xu Feng, Bin Yu, Zhen Chen, Shimin Wang, Ling Yin, Lisha Mou, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

DNA damage-activated signaling pathways are critical for coordinating multiple cellular processes, which must be tightly regulated to maintain genome stability. To provide a comprehensive and unbiased perspective of DNA damage response (DDR) signaling pathways, we performed 30 fluorescence-activated cell sorting (FACS)-based genome-wide CRISPR screens in human cell lines with antibodies recognizing distinct endogenous DNA damage signaling proteins to identify critical regulators involved in DDR. We discovered that proteasome-mediated processing is an early and prerequisite event for cells to trigger camptothecin- and etoposide-induced DDR signaling. Furthermore, we identified PRMT1 and PRMT5 as modulators that regulate ATM protein level. Moreover, we discovered …

Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales

Faculty, Staff and Student Publications

Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, …

Moving The Pendulum For Glioblastoma Treatment: One Injection At A Time, Xizi Wu, Christopher Alvarez-Breckenridge

Faculty, Staff and Student Publications

Despite advances, glioblastoma is characterized by exceptionally high rates of recurrence and resistance to therapy. This commentary remarks on the recently published article by Maruyama et al, which reports the PMDA review of G47Δ injection for malignant glioma, in which the efficacy and safety results of G47Δ were evaluated and approval conditions clarified.

Genotype Error Due To Low-Coverage Sequencing Induces Uncertainty In Polygenic Scoring, Ella Petter, Yi Ding, Kangcheng Hou, Arjun Bhattacharya, Alexander Gusev, Noah Zaitlen, Bogdan Pasaniuc

Faculty, Staff and Student Publications

Polygenic scores (PGSs) have emerged as a standard approach to predict phenotypes from genotype data in a wide array of applications from socio-genomics to personalized medicine. Traditional PGSs assume genotype data to be error-free, ignoring possible errors and uncertainties introduced from genotyping, sequencing, and/or imputation. In this work, we investigate the effects of genotyping error due to low coverage sequencing on PGS estimation. We leverage SNP array and low-coverage whole-genome sequencing data (lcWGS, median coverage 0.04×) of 802 individuals from the Dana-Farber PROFILE cohort to show that PGS error correlates with sequencing depth (p = 1.2 × 10

Safety And Efficacy Of Immune Checkpoint Inhibitors In Patients With Cancer And Viral Hepatitis: The Md Anderson Cancer Center Experience, Mirella Nardo, Bulent Yilmaz, Blessie Elizabeth Nelson, Harrys A Torres, Lan Sun Wang, Bruno Palma Granwehr, Juhee Song, Hanna R F Dalla Pria, Van A Trinh, Isabella C Glitza Oliva, Sapna P Patel, Nizar M Tannir, Ahmed Omar Kaseb, Mehmet Altan, Sunyoung S Lee, Ethan Miller, Hao Zhang, Bettzy A Stephen, Aung Naing

Faculty, Staff and Student Publications

Background: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment.

Materials and methods: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019.

Results: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. …

Beyond The Exome: What’S Next In Diagnostic Testing For Mendelian Conditions, Monica H Wojcik, Chloe M Reuter, Shruti Marwaha, Medhat Mahmoud, Michael H Duyzend, Hayk Barseghyan, Bo Yuan, Philip M Boone, Emily E Groopman, Emmanuèle C Délot, Deepti Jain, Alba Sanchis-Juan, Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium, Lea M Starita, Michael Talkowski, Stephen B Montgomery, Michael J Bamshad, Jessica X Chong, Matthew T Wheeler, Seth I Berger, Anne O'Donnell-Luria, Fritz J Sedlazeck, Danny E Miller

Faculty, Staff and Student Publications

Despite advances in clinical genetic testing, including the introduction of exome sequencing (ES), more than 50% of individuals with a suspected Mendelian condition lack a precise molecular diagnosis. Clinical evaluation is increasingly undertaken by specialists outside of clinical genetics, often occurring in a tiered fashion and typically ending after ES. The current diagnostic rate reflects multiple factors, including technical limitations, incomplete understanding of variant pathogenicity, missing genotype-phenotype associations, complex gene-environment interactions, and reporting differences between clinical labs. Maintaining a clear understanding of the rapidly evolving landscape of diagnostic tests beyond ES, and their limitations, presents a challenge for non-genetics professionals. …

Proteogenomic Analysis Of Chemo-Refractory High-Grade Serous Ovarian Cancer, Shrabanti Chowdhury, Jacob J Kennedy, Richard G Ivey, Oscar D Murillo, Noshad Hosseini, Xiaoyu Song, Francesca Petralia, Anna Calinawan, Sara R Savage, Anna B Berry, Boris Reva, Umut Ozbek, Azra Krek, Weiping Ma, Felipe Da Veiga Leprevost, Jiayi Ji, Seungyeul Yoo, Chenwei Lin, Uliana J Voytovich, Yajue Huang, Sun-Hee Lee, Lindsay Bergan, Travis D Lorentzen, Mehdi Mesri, Henry Rodriguez, Andrew N Hoofnagle, Zachary T Herbert, Alexey I Nesvizhskii, Bing Zhang, Jeffrey R Whiteaker, David Fenyo, Wilson Mckerrow, Joshua Wang, Stephan C Schürer, Vasileios Stathias, X Steven Chen, Mary Helen Barcellos-Hoff, Timothy K Starr, Boris J Winterhoff, Andrew C Nelson, Samuel C Mok, Scott H Kaufmann, Charles Drescher, Marcin Cieslik, Pei Wang, Michael J Birrer, Amanda G Paulovich

Faculty, Staff and Student Publications

To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) …

2022 St. John’S University Biennial Poverty Conference Abstracts, Patrick Griffin, John M. Conry

Journal of Vincentian Social Action

No abstract provided.

Justice House At Niagara University: An Emerging Approach To Teaching Vincentian Social Justice During And After The Covid-19 Pandemic, Kevin A. Hinkley

Journal of Vincentian Social Action

Some commentators have predicted that the disruptive effects of the COVID-19 pandemic will transform the landscape of higher education in the United States. For example, Scott Galloway, Professor of Marketing at NYU Stern School of Business, predicts that most U.S. colleges and universities will either “go out of business or become a shadow of themselves.” Professor Galloway argues that the few elite universities that survive will enter into corporate partnerships with Big Tech companies such as Google, Apple, and Meta. From this perspective, for the overwhelming majority of U.S. colleges and universities there won’t be a “post-pandemic recovery”— at least …

Accepting Educational Responsibility For Social Justice: Homeless Mothers’ And Children’S Need Of Education About Health And Nutrition, Smita Guha

Journal of Vincentian Social Action

The goal is to improve health and nutrition among new mothers and their children who were living in shelters. The mothers received workshops and booklets consisting of information, quick and healthy recipes, and learned how to prepare home-made meals with a low budget. The mothers realized nutritious foods are important for them and their children. They learned how to manage time to make nutritious food at the residence. Children regardless of their background, are our future and we need to pay attention to their needs now so that future problems could be prevented. The significance of this study is immense …

Cancer Clinical Trials: The Role Of Healthcare Providers In Addressing Inequitable Racial/Ethnic Minority Representation In Biomedical Research, Jilian Maxine Jalipa Frianela, Gillian Leasunia Katoanga

Journal of Vincentian Social Action

No abstract provided.

Exploring Sexual Health Education Disparities Among Latina Immigrants In Jackson Heights, N.Y., Maria Camila Lopez, Hira Shafeeq

Journal of Vincentian Social Action

The purpose of the current study is to explore the factors that influence sexual health decisions of female Latina immigrants with low socioeconomic status in an urban area. We aimed to evaluate the possible preventive steps to lower their risk of contracting STDs. The need for this study was highlighted by research findings that suggest that health disparities among Hispanic immigrants have had a significant impact on their poor quality of life due to lack of proper access to medical care and misdiagnosis due to differences in risk factors and manifestations of the disease. Sexual health is a constant issue …

Mental Health Stigma As A Sociocultural Complex Within Panamanian Culture, Arielle Sanders

Journal of Vincentian Social Action

The purpose of this study is to examine mental health stigma within the sociocultural context shared by members of the Panamanian population. Mental health stigma is complex because it manifests itself differently according to the cultural context in which it is experienced. Culture informs individual beliefs, behaviors, and attitudes regarding how a person should live within their immediate household and within society. This social conditioning is accomplished through a variety of means, including the passing down of social norms, traditions, and customs. Ultimately, these cultural characteristics encourage socially acceptable behaviors while simultaneously discouraging undesirable behaviors in order to maintain group …

Demystifying Research For Undergraduate Students: An Avenue To Participate In Mission-Based Research, Hira Shafeeq

Journal of Vincentian Social Action

No abstract provided.

Editors

Journal of Vincentian Social Action

No abstract provided.

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Journal of Vincentian Social Action

No abstract provided.

Cover

Journal of Vincentian Social Action

No abstract provided.

Genetic Insights Into Resting Heart Rate And Its Role In Cardiovascular Disease, Yordi J Van De Vegte, Ruben N Eppinga, M Yldau Van Der Ende, Yanick P Hagemeijer, Yuvaraj Mahendran, Elias Salfati, Albert V Smith, Vanessa Y Tan, Dan E Arking, Ioanna Ntalla, Emil V Appel, Claudia Schurmann, Jennifer A Brody, Rico Rueedi, Ozren Polasek, Gardar Sveinbjornsson, Cecile Lecoeur, Claes Ladenvall, Jing Hua Zhao, Aaron Isaacs, Lihua Wang, Jian'an Luan, Shih-Jen Hwang, Nina Mononen, Kirsi Auro, Anne U Jackson, Lawrence F Bielak, Linyao Zeng, Nabi Shah, Maria Nethander, Archie Campbell, Tuomo Rankinen, Sonali Pechlivanis, Lu Qi, Wei Zhao, Federica Rizzi, Toshiko Tanaka, Antonietta Robino, Massimiliano Cocca, Leslie Lange, Martina Müller-Nurasyid, Carolina Roselli, Weihua Zhang, Marcus E Kleber, Xiuqing Guo, Henry J Lin, Francesca Pavani, Tessel E Galesloot, Raymond Noordam, Yuri Milaneschi, Katharina E Schraut, Marcel Den Hoed, Frauke Degenhardt, Stella Trompet, Marten E Van Den Berg, Giorgio Pistis, Yih-Chung Tham, Stefan Weiss, Xueling S Sim, Hengtong L Li, Peter J Van Der Most, Ilja M Nolte, Leo-Pekka Lyytikäinen, M Abdullah Said, Daniel R Witte, Carlos Iribarren, Lenore Launer, Susan M Ring, Paul S De Vries, Peter Sever, Allan Linneberg, Erwin P Bottinger, Sandosh Padmanabhan, Bruce M Psaty, Nona Sotoodehnia, Ivana Kolcic, Dcct/Edic Research Group, David O Arnar, Daniel F Gudbjartsson, Hilma Holm, Beverley Balkau, Claudia T Silva, Christopher H Newton-Cheh, Kjell Nikus, Perttu Salo, Karen L Mohlke, Patricia A Peyser, Heribert Schunkert, Mattias Lorentzon, Jari Lahti, Dabeeru C Rao, Marilyn C Cornelis, Jessica D Faul, Jennifer A Smith, Katarzyna Stolarz-Skrzypek, Stefania Bandinelli, Maria Pina Concas, Gianfranco Sinagra, Thomas Meitinger, Melanie Waldenberger, Moritz F Sinner, Konstantin Strauch, Graciela E Delgado, Kent D Taylor, Jie Yao, Luisa Foco, Olle Melander, Jacqueline De Graaf, Renée De Mutsert, Eco J C De Geus, Åsa Johansson, Peter K Joshi, Lars Lind, Andre Franke, Peter W Macfarlane, Kirill V Tarasov, Nicholas Tan, Stephan B Felix, E-Shyong Tai, Debra Q Quek, Harold Snieder, Johan Ormel, Martin Ingelsson, Cecilia Lindgren, Andrew P Morris, Olli T Raitakari, Torben Hansen, Themistocles Assimes, Vilmundur Gudnason, Nicholas J Timpson, Alanna C Morrison, Patricia B Munroe, David P Strachan, Niels Grarup, Ruth J F Loos, Susan R Heckbert, Peter Vollenweider, Caroline Hayward, Kari Stefansson, Philippe Froguel, Leif Groop, Nicholas J Wareham, Cornelia M Van Duijn, Mary F Feitosa, Christopher J O'Donnell, Mika Kähönen, Markus Perola, Michael Boehnke, Sharon L R Kardia, Jeanette Erdmann, Colin N A Palmer, Claes Ohlsson, David J Porteous, Johan G Eriksson, Claude Bouchard, Susanne Moebus, Peter Kraft, David R Weir, Daniele Cusi, Luigi Ferrucci, Sheila Ulivi, Giorgia Girotto, Adolfo Correa, Stefan Kääb, Annette Peters, John C Chambers, Jaspal S Kooner, Winfried März, Jerome I Rotter, Andrew A Hicks, J Gustav Smith, Lambertus A L M Kiemeney, Dennis O Mook-Kanamori, Brenda W J H Penninx, Ulf Gyllensten, James F Wilson, Stephen Burgess, Johan Sundström, Wolfgang Lieb, J Wouter Jukema, Mark Eijgelsheim, Edward L M Lakatta, Ching-Yu Cheng, Marcus Dörr, Tien-Yin Wong, Charumathi Sabanayagam, Albertine J Oldehinkel, Harriette Riese, Terho Lehtimäki, Niek Verweij, Pim Van Der Harst

Faculty, Staff and Student Publications

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample …