Medicine and Health Sciences Commons^™

Environmental Magnesium Ion Affects Global Gene Expression, Motility, Biofilm Formation And Virulence Of Vibrio Parahaemolyticus, Xue Li, Xiaobai Zhang, Miaomiao Zhang, Xi Luo, Tingting Zhang, Xianjin Liu, Renfei Lu, Yiquan Zhang

Journal Articles

No abstract provided.

Genetic Variants For Head Size Share Genes And Pathways With Cancer, Maria J Knol, Raymond A Poot, Tavia E Evans, Claudia L Satizabal, Aniket Mishra, Muralidharan Sargurupremraj, Sandra Van Der Auwera, Marie-Gabrielle Duperron, Xueqiu Jian, Isabel C Hostettler, Dianne H K Van Dam-Nolen, Sander Lamballais, Mikolaj A Pawlak, Cora E Lewis, Amaia Carrion-Castillo, Theo G M Van Erp, Céline S Reinbold, Jean Shin, Markus Scholz, Asta K Håberg, Anders Kämpe, Gloria H Y Li, Reut Avinun, Joshua R Atkins, Fang-Chi Hsu, Alyssa R Amod, Max Lam, Ami Tsuchida, Mariël W A Teunissen, Nil Aygün, Yash Patel, Dan Liang, Alexa S Beiser, Frauke Beyer, Joshua C Bis, Daniel Bos, R Nick Bryan, Robin Bülow, Svenja Caspers, Gwenaëlle Catheline, Charlotte A M Cecil, Shareefa Dalvie, Jean-François Dartigues, Charles Decarli, Maria Enlund-Cerullo, Judith M Ford, Barbara Franke, Barry I Freedman, Nele Friedrich, Melissa J Green, Simon Haworth, Catherine Helmer, Per Hoffmann, Georg Homuth, M Kamran Ikram, Clifford R Jack, Neda Jahanshad, Christiane Jockwitz, Yoichiro Kamatani, Annchen R Knodt, Shuo Li, Keane Lim, W T Longstreth, Fabio Macciardi, Outi Mäkitie, Bernard Mazoyer, Sarah E Medland, Susumu Miyamoto, Susanne Moebus, Thomas H Mosley, Ryan Muetzel, Thomas W Mühleisen, Manabu Nagata, Soichiro Nakahara, Nicholette D Palmer, Zdenka Pausova, Adrian Preda, Yann Quidé, William R Reay, Gennady V Roshchupkin, Reinhold Schmidt, Pamela J Schreiner, Kazuya Setoh, Chin Yang Shapland, Stephen Sidney, Beate St Pourcain, Jason L Stein, Yasuharu Tabara, Alexander Teumer, Anne Uhlmann, Aad Van Der Lugt, Meike W Vernooij, David J Werring, B Gwen Windham, A Veronica Witte, Katharina Wittfeld, Qiong Yang, Kazumichi Yoshida, Han G Brunner, Quentin Le Grand, Kang Sim, Dan J Stein, Donald W Bowden, Murray J Cairns, Ahmad R Hariri, Ching-Lung Cheung, Sture Andersson, Arno Villringer, Tomas Paus, Sven Cichon, Vince D Calhoun, Fabrice Crivello, Lenore J Launer, Tonya White, Peter J Koudstaal, Henry Houlden, Myriam Fornage, Fumihiko Matsuda, Hans J Grabe, M Arfan Ikram, Stéphanie Debette, Paul M Thompson, Sudha Seshadri, Hieab H H Adams

Journal Articles

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size …

An Approach To Identify Gene-Environment Interactions And Reveal New Biological Insight In Complex Traits, Xiaofeng Zhu, Yihe Yang, Noah Lorincz-Comi, Gen Li, Amy R Bentley, Paul S De Vries, Michael Brown, Alanna C Morrison, Charles N Rotimi, W James Gauderman, Dabeeru C Rao, Hugues Aschard

Journal Articles

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. to address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci …

Unsupervised Deep Representation Learning Enables Phenotype Discovery For Genetic Association Studies Of Brain Imaging, Khush Patel, Ziqian Xie, Hao Yuan, Sheikh Muhammad Saiful Islam, Yaochen Xie, Wei He, Wanheng Zhang, Assaf Gottlieb, Han Chen, Luca Giancardo, Alexander Knaack, Evan Fletcher, Myriam Fornage, Shuiwang Ji, Degui Zhi

Journal Articles

Understanding the genetic architecture of brain structure is challenging, partly due to difficulties in designing robust, non-biased descriptors of brain morphology. Until recently, brain measures for genome-wide association studies (GWAS) consisted of traditionally expert-defined or software-derived image-derived phenotypes (IDPs) that are often based on theoretical preconceptions or computed from limited amounts of data. Here, we present an approach to derive brain imaging phenotypes using unsupervised deep representation learning. We train a 3-D convolutional autoencoder model with reconstruction loss on 6130 UK Biobank (UKBB) participants' T1 or T2-FLAIR (T2) brain MRIs to create a 128-dimensional representation known as Unsupervised Deep learning …

A Multitrait Genetic Study Of Hemostatic Factors And Hemorrhagic Transformation After Stroke Treatment, Cristina Gallego-Fabrega, Gerard Temprano-Sagrera, Jara Cárcel-Márquez, Elena Muiño, Natalia Cullell, Miquel Lledós, Laia Llucià-Carol, Jesús M Martin-Campos, Tomás Sobrino, José Castillo, Mònica Millán, Lucía Muñoz-Narbona, Elena López-Cancio, Marc Ribó, Jose Alvarez-Sabin, Jordi Jiménez-Conde, Jaume Roquer, Silvia Tur, Victor Obach, Juan F Arenillas, Tomas Segura, Gemma Serrano-Heras, Joan Marti-Fabregas, Marimar Freijo-Guerrero, Francisco Moniche, Maria Del Mar Castellanos, Alanna C Morrison, Nicholas L Smith, Paul S De Vries, Israel Fernández-Cadenas, Maria Sabater-Lleal

Journal Articles

BACKGROUND: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis.

OBJECTIVES: to investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment.

METHODS: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed …

Association Between Regulatory T Cells And Ischemic Heart Disease: A Mendelian Randomization Study, Yucheng Hou, Ke Si, Jingyue Yang, Tan Liu, Basel Abdelazeem, Nonthikorn Theerasuwipakorn, Jingwei Zhao, Zhenya Shen

Journal Articles

BACKGROUND: An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy …

Contextualizing The Revised Patient Perception Of Patient-Centeredness (Pppc-R) Scale In Primary Healthcare Settings: A Validity And Reliability Evaluation Study, Yiyuan Cai, Pengfei Guo, Jiong Tu, Mengyao Hu, Lingrui Liu, Bridget L Ryan, Jing Liao, Rubee Dev, Yiran Li, Tianyu Huang, Ruilin Wang, Li Kuang, Ruonan Huang, Xinfang Li, Edmundo Roberto Melipillán, Shuaixiang Zhao, Wenjun He, Xiaohui Wang, Nan Zhang, Dong Roman Xu

Journal Articles

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations.

AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale.

DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis …

Factors Associated With Blood Mercury Concentrations And Their Interactions With Three Glutathione S-Transferase Genes (Gstt1, Gstm1, And Gstp1): An Exposure Assessment Study Of Typically Developing Jamaican Children, Sheikh Farzana Zaman, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare Pellington, Katherine A Loveland, Mohammad H Rahbar

Journal Articles

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.

METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general …

Factors Associated With Blood Mercury Concentrations And Their Interactions With Three Glutathione S-Transferase Genes (Gstt1, Gstm1, And Gstp1): An Exposure Assessment Study Of Typically Developing Jamaican Children, Sheikh Farzana Zaman, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare Pellington, Katherine A Loveland, Mohammad H Rahbar

Journal Articles

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.

METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general …

The Use Of Cardiac Magnetic Resonance In Hypertrophic Cardiomyopathy Over The Past 10 Years [2013-2023]: A Citespace-Based Bibliometric Analysis, Mengyao Hu, Yu Shen, Yipei Song, Shuhao Li, Pei Yang, Ao Kan, Qiming Fang, Yun Peng, Haibo Ren, Yajing Zhang, Lianggeng Gong

Journal Articles

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder characterized by the hypertrophy of a segment of the myocardium. Cardiac magnetic resonance (CMR) has been widely used in the assessment of HCM. However, no bibliometric assessment has been conducted on the progress of research in this field. This study thus aimed to examine the current state of research into the application of CMR in HCM and the hotspots and trends that have emerged in this field over the past decade.

METHODS: A systematic search was conducted on the Web of Science regarding CMR in the assessment of HCM. The …

Unraveling The Prognostic Significance Of Rgs Gene Family In Gastric Cancer And The Potential Implication Of Rgs4 In Regulating Tumor-Infiltrating Fibroblast, Yalan Yang, Siyuan Xing, Xi Luo, Lulu Guan, Yao Lu, Yiting Wang, Feng Wang

Journal Articles

Regulator of G-protein signaling (RGS) proteins are regulators of signal transduction mediated by G protein-coupled receptors (GPCRs). Current studies have shown that some molecules in the RGS gene family are related to the occurrence, development and poor prognosis of malignant tumors. However, the RGS gene family has been rarely studied in gastric cancer. In this study, we explored the mutation and expression profile of RGS gene family in gastric cancer, and evaluated the prognostic value of RGS expression. Then we established a prognostic model based on RGS gene family and performed functional analysis. Further studies showed that RGS4, as an …

Chromosome 10q2432 Variants Associate With Brain Arterial Diameters In Diverse Populations: A Genome-Wide Association Study, Minghua Liu, Farid Khasiyev, Sanjeev Sariya, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Emy A Thomas, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Saima Hilal, Bruce A Wasserman, Giuseppe Tosto, Myriam Fornage, Jose Gutierrez

Journal Articles

BACKGROUND: Brain arterial diameters (BADs) are novel imaging biomarkers of cerebrovascular disease, cognitive decline, and dementia. Traditional vascular risk factors have been associated with BADs, but whether there may be genetic determinants of BADs is unknown.

METHODS AND RESULTS: The authors studied 4150 participants from 6 geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). Brain arterial diameters for 13 segments were measured and averaged to obtain a global measure of BADs as well as the posterior and anterior circulations. A genome-wide association study revealed 14 variants at one locus associated with global BAD at genome-wide …

A Double-Robust Test For High-Dimensional Gene Coexpression Networks Conditioning On Clinical Information, Maomao Ding, Ruosha Li, Jin Qin, Jing Ning

Journal Articles

It has been increasingly appealing to evaluate whether expression levels of two genes in a gene coexpression network are still dependent given samples' clinical information, in which the conditional independence test plays an essential role. For enhanced robustness regarding model assumptions, we propose a class of double-robust tests for evaluating the dependence of bivariate outcomes after controlling for known clinical information. Although the proposed test relies on the marginal density functions of bivariate outcomes given clinical information, the test remains valid as long as one of the density functions is correctly specified. Because of the closed-form variance formula, the proposed …

Type 2 Diabetes Modifies The Association Of Cad Genomic Risk Variants With Subclinical Atherosclerosis, Natalie R Hasbani, Kenneth E Westerman, Soo Heon Kwak, Han Chen, Xihao Li, Daniel Di Corpo, Jennifer Wessel, Joshua C Bis, Chloè Sarnowski, Peitao Wu, Lawrence F Bielak, Xiuqing Guo, Nancy Heard-Costa, Gregory L Kinney, Michael C Mahaney, May E Montasser, Nicholette D Palmer, Laura M Raffield, James G Terry, Lisa R Yanek, Jessica Bon, Donald W Bowden, Jennifer A Brody, Ravindranath Duggirala, David R Jacobs, Rita R Kalyani, Leslie A Lange, Braxton D Mitchell, Jennifer A Smith, Kent D Taylor, April P Carson, Joanne E Curran, Myriam Fornage, Barry I Freedman, Stacey Gabriel, Richard A Gibbs, Namrata Gupta, Sharon L R Kardia, Brian G Kral, Zeineen Momin, Anne B Newman, Wendy S Post, Karine A Viaud-Martinez, Kendra A Young, Lewis C Becker, Alain G Bertoni, John Blangero, John J Carr, Katherine Pratte, Bruce M Psaty, Stephen S Rich, Joseph C Wu, Rajeev Malhotra, Patricia A Peyser, Alanna C Morrison, Ramachandran S Vasan, Xihong Lin, Jerome I Rotter, James B Meigs, Alisa K Manning, Paul S De Vries

Journal Articles

BACKGROUND: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.

METHODS: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 …

Identification Of Circulating Proteins Associated With General Cognitive Function Among Middle-Aged And Older Adults, Adrienne Tin, Alison E Fohner, Qiong Yang, Jennifer A Brody, Gail Davies, Jie Yao, Dan Liu, Ilana Caro, Joni V Lindbohm, Michael R Duggan, Osorio Meirelles, Sarah E Harris, Valborg Gudmundsdottir, Adele M Taylor, Albert Henry, Alexa S Beiser, Ali Shojaie, Annabell Coors, Annette L Fitzpatrick, Claudia Langenberg, Claudia L Satizabal, Colleen M Sitlani, Eleanor Wheeler, Elliot M Tucker-Drob, Jan Bressler, Josef Coresh, Joshua C Bis, Julián Candia, Lori L Jennings, Maik Pietzner, Mark Lathrop, Oscar L Lopez, Paul Redmond, Robert E Gerszten, Stephen S Rich, Susan R Heckbert, Thomas R Austin, Timothy M Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I Rotter, Keenan A Walker, Luigi Ferrucci, Mika Kivimäki, Monique M B Breteler, Simon R Cox, Stephanie Debette, Thomas H Mosley, Vilmundur G Gudnason, Lenore J Launer, Bruce M Psaty, Sudha Seshadri, Myriam Fornage

Journal Articles

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Estimating Heritability Explained By Local Ancestry And Evaluating Stratification Bias In Admixture Mapping From Summary Statistics, Tsz Fung Chan, Xinyue Rui, David V Conti, Myriam Fornage, Mariaelisa Graff, Jeffrey Haessler, Christopher Haiman, Heather M Highland, Su Yon Jung, Eimear E Kenny, Charles Kooperberg, Loic Le Marchand, Kari E North, Ran Tao, Genevieve Wojcik, Christopher R Gignoux, Charleston W K Chiang, Nicholas Mancuso

Journal Articles

The heritability explained by local ancestry markers in an admixed population (h

Utilization And Predictors Of Adjuvant Metformin For Children And Adolescents On Mixed Receptor Antagonists (Second-Generation Antipsychotics), Hua Chen, Ning Lyu, Wenyaw Chan, Austin De La Cruz, Chadi Calarge

Journal Articles

OBJECTIVE: to examine utilization and predictors of adjuvant metformin among pediatric recipients of second-generation antipsychotics (SGAs) (mixed receptor antagonist).

METHOD: This study used 2016-2021 data of a national electronic medical record database. Eligible participants were children aged 6 to 17 with a new SGA prescription for at least 90 days. Predictors of prescribing adjuvant metformin in general and to nonobese pediatric SGA recipients in particular were assessed using conditional logistic regression and logistic regression analyses, respectively.

RESULTS: Of 30,009 pediatric SGA recipients identified, 2.3% (n = 785) received adjuvant metformin. Among 597 participants with a body mass index z score …

Mosaic Chromosomal Alterations In Blood Across Ancestries Using Whole-Genome Sequencing, Yasminka A Jakubek, Ying Zhou, Adrienne Stilp, Jason Bacon, Justin W Wong, Zuhal Ozcan, Donna Arnett, Kathleen Barnes, Joshua C Bis, Eric Boerwinkle, Jennifer A Brody, April P Carson, Daniel I Chasman, Jiawen Chen, Michael Cho, Matthew P Conomos, Nancy Cox, Margaret F Doyle, Myriam Fornage, Xiuqing Guo, Sharon L R Kardia, Joshua P Lewis, Ruth J F Loos, Xiaolong Ma, Mitchell J Machiela, Taralynn M Mack, Rasika A Mathias, Braxton D Mitchell, Josyf C Mychaleckyj, Kari North, Nathan Pankratz, Patricia A Peyser, Michael H Preuss, Bruce Psaty, Laura M Raffield, Ramachandran S Vasan, Susan Redline, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Jennifer A Smith, Aaron P Smith, Margaret Taub, Kent D Taylor, Jeong Yun, Yun Li, Pinkal Desai, Alexander G Bick, Alexander P Reiner, Paul Scheet, Paul L Auer

Journal Articles

Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. …

Multi-Tissue Epigenetic Analysis Identifies Distinct Associations Underlying Insulin Resistance And Alzheimer's Disease At Cpt1a Locus, Chloé Sarnowski, Tianxiao Huan, Yiyi Ma, Roby Joehanes, Alexa Beiser, Charles S Decarli, Nancy L Heard-Costa, Daniel Levy, Honghuang Lin, Ching-Ti Liu, Chunyu Liu, James B Meigs, Claudia L Satizabal, Jose C Florez, Marie-France Hivert, Josée Dupuis, Philip L De Jager, David A Bennett, Sudha Seshadri, Alanna C Morrison

Journal Articles

BACKGROUND: Insulin resistance (IR) is a major risk factor for Alzheimer's disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD.

METHODS: We conducted an epigenome-wide association study of IR, quantified using the homeostatic model assessment of IR (HOMA-IR) and adjusted for body mass index, in 3,167 participants from the Framingham Heart Study (FHS) without type 2 diabetes at the time of blood draw used for methylation measurement. We identified …

Association Between Whole Blood-Derived Mitochondrial Dna Copy Number, Low-Density Lipoprotein Cholesterol, And Cardiovascular Disease Risk, Xue Liu, Xianbang Sun, Yuankai Zhang, Wenqing Jiang, Meng Lai, Kerri L Wiggins, Laura M Raffield, Lawrence F Bielak, Wei Zhao, Achilleas Pitsillides, Jeffrey Haessler, Yinan Zheng, Thomas W Blackwell, Jie Yao, Xiuqing Guo, Yong Qian, Bharat Thyagarajan, Nathan Pankratz, Stephen S Rich, Kent D Taylor, Patricia A Peyser, Susan R Heckbert, Sudha Seshadri, Eric Boerwinkle, Megan L Grove, Nicholas B Larson, Jennifer A Smith, Ramachandran S Vasan, Annette L Fitzpatrick, Myriam Fornage, Jun Ding, April P Carson, Goncalo Abecasis, Josée Dupuis, Alexander Reiner, Charles Kooperberg, Lifang Hou, Bruce M Psaty, James G Wilson, Daniel Levy, Jerome I Rotter, Joshua C Bis, Claudia L Satizabal, Dan E Arking, Chunyu Liu

Journal Articles

Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods and Results We performed cross-sectional and prospective association analyses of blood-derived mtDNA CN and cardiovascular disease outcomes in 27 316 participants in 8 cohorts of multiple racial and ethnic groups with whole-genome sequencing. We also performed Mendelian randomization to explore causal relationships of mtDNA CN with coronary heart disease (CHD) and cardiometabolic risk factors (obesity, diabetes, hypertension, and hyperlipidemia).

Next-Generation Crispr Gene-Drive Systems Using Cas12a Nuclease, Sara Sanz Juste, Emily M Okamoto, Christina Nguyen, Xuechun Feng, Víctor López Del Amo

Journal Articles

One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of alternative gene drive arrangements. Yet, other nucleases such as the temperature sensitive Cas12a have not been explored for gene drive designs in insects. to address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated …

Multivariate Genetic Analysis Of Personality And Cognitive Traits Reveals Abundant Pleiotropy, Guy Hindley, Alexey A Shadrin, Dennis Van Der Meer, Nadine Parker, Weiqiu Cheng, Kevin S O'Connell, Shahram Bahrami, Aihua Lin, Naz Karadag, Børge Holen, Thomas Bjella, Ian J Deary, Gail Davies, W David Hill, Jan Bressler, Sudha Seshadri, Chun Chieh Fan, Torill Ueland, Srdjan Djurovic, Olav B Smeland, Oleksandr Frei, Anders M Dale, Ole A Andreassen

Journal Articles

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies …

T-Cell Receptor Beta Variable Gene Polymorphism Predicts Immune-Related Adverse Events During Checkpoint Blockade Immunotherapy, Bettzy Stephen, Joud Hajjar, Shrutii Sarda, Dzifa Yawa Duose, Jeffrey M Conroy, Carl Morrison, Anas Alshawa, Mingxuan Xu, Abdulrazzak Zarifa, Sapna P Patel, Ying Yuan, Evan Kwiatkowski, Linghua Wang, Jordi Rodon Ahnert, Siqing Fu, Funda Meric-Bernstam, Geoffrey M Lowman, Timothy Looney, Aung Naing

Journal Articles

BACKGROUND: Immune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the …

Rare Variant Enrichment Analysis Supports, Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M Grochowski, Ruizhi Duan, Jawid M Fatih, Moez Dawood, Sejal Salvi, Shalini N Jhangiani, Donna M Muzny, André Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A Wise, Jennifer E Dietrich, Ignatia B Van Den Veyver, Antigone S Dimas, Sara Brucker, V Reid Sutton, Richard A Gibbs, Stylianos E Antonarakis, Nan Wu, Zeynep H Coban-Akdemir, Lan Zhu, Jennifer E Posey, James R Lupski

Journal Articles

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only

Biallelic Variants In Adamts15 Cause A Novel Form Of Distal Arthrogryposis, Felix Boschann, Ozgur Cogulu, Davut Pehlivan, Saranya Balachandran, Pedro Vallecillo-Garcia, Christopher M Grochowski, Nils R Hansmeier, Zeynep H Coban Akdemir, Cesar A Prada-Medina, Ayca Aykut, Björn Fischer-Zirnsak, Simon Badura, Burak Durmaz, Ferda Ozkinay, René Hägerling, Jennifer E Posey, Sigmar Stricker, Gabriele Gillessen-Kaesbach, Malte Spielmann, Denise Horn, Knut Brockmann, James R Lupski, Uwe Kornak, Julia Schmidt

Journal Articles

No abstract provided.

Systemic Interindividual Epigenetic Variation In Humans Is Associated With Transposable Elements And Under Strong Genetic Control, Chathura J Gunasekara, Harry Mackay, C Anthony Scott, Shaobo Li, Eleonora Laritsky, Maria S Baker, Sandra L Grimm, Goo Jun, Yumei Li, Rui Chen, Joseph L Wiemels, Cristian Coarfa, Robert A Waterland

Journal Articles

BACKGROUND: Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition.

RESULTS: We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program. At CoRSIVs, DNA methylation in peripheral blood correlates with …

Genome-Wide Mendelian Randomization Identifies Putatively Causal Gut Microbiota For Multiple Peptic Ulcer Diseases, Jingwei Zhao, Yucheng Hou, Tianyi Xie, Yizhang Zhu, Xinyi Feng, Yong Zhang, Ziyi Yang, Wei Gong

Journal Articles

OBJECTIVE: The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation.

DESIGN: The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting …

Whole Genome Sequence Analysis Of Apparent Treatment Resistant Hypertension Status In Participants From The Trans-Omics For Precision Medicine Program, Nicole D Armstrong, Vinodh Srinivasasainagendra, Farah Ammous, Themistocles L Assimes, Amber L Beitelshees, Jennifer Brody, Brian E Cade, Yii-Der Ida Chen, Han Chen, Paul S De Vries, James S Floyd, Nora Franceschini, Xiuqing Guo, Jacklyn N Hellwege, John S House, Chii-Min Hwu, Sharon L R Kardia, Ethan M Lange, Leslie A Lange, Caitrin W Mcdonough, May E Montasser, Jeffrey R O'Connell, Megan M Shuey, Xiao Sun, Rikki M Tanner, Zhe Wang, Wei Zhao, April P Carson, Todd L Edwards, Tanika N Kelly, Eimear E Kenny, Charles Kooperberg, Ruth J F Loos, Alanna C Morrison, Alison Motsinger-Reif, Bruce M Psaty, Dabeeru C Rao, Susan Redline, Stephen S Rich, Jerome I Rotter, Jennifer A Smith, Albert V Smith, Marguerite R Irvin, Donna K Arnett

Journal Articles

No abstract provided.

Gene-Educational Attainment Interactions In A Multi-Population Genome-Wide Meta-Analysis Identify Novel Lipid Loci, Lisa De Las Fuentes, Karen L Schwander, Michael R Brown, Amy R Bentley, Thomas W Winkler, Yun Ju Sung, Patricia B Munroe, Clint L Miller, Hugo Aschard, Stella Aslibekyan, Traci M Bartz, Lawrence F Bielak, Jin Fang Chai, Ching-Yu Cheng, Rajkumar Dorajoo, Mary F Feitosa, Xiuqing Guo, Fernando P Hartwig, Andrea Horimoto, Ivana Kolčić, Elise Lim, Yongmei Liu, Alisa K Manning, Jonathan Marten, Solomon K Musani, Raymond Noordam, Sandosh Padmanabhan, Tuomo Rankinen, Melissa A Richard, Paul M Ridker, Albert V Smith, Dina Vojinovic, Alan B Zonderman, Maris Alver, Mathilde Boissel, Kaare Christensen, Barry I Freedman, Chuan Gao, Franco Giulianini, Sarah E Harris, Meian He, Fang-Chi Hsu, Brigitte Kühnel, Federica Laguzzi, Xiaoyin Li, Leo-Pekka Lyytikäinen, Ilja M Nolte, Alaitz Poveda, Rainer Rauramaa, Muhammad Riaz, Antonietta Robino, Tamar Sofer, Fumihiko Takeuchi, Bamidele O Tayo, Peter J Van Der Most, Niek Verweij, Erin B Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Yiqiang Zhan, Najaf Amin, Dan E Arking, Christie Ballantyne, Eric Boerwinkle, Jennifer A Brody, Ulrich Broeckel, Archie Campbell, Mickaël Canouil, Xiaoran Chai, Yii-Der Ida Chen, Xu Chen, Kumaraswamy Naidu Chitrala, Maria Pina Concas, Ulf De Faire, Renée De Mutsert, H Janaka De Silva, Paul S De Vries, Ahn Do, Jessica D Faul, Virginia Fisher, James S Floyd, Terrence Forrester, Yechiel Friedlander, Giorgia Girotto, C Charles Gu, Göran Hallmans, Sami Heikkinen, Chew-Kiat Heng, Georg Homuth, Steven Hunt, M Arfan Ikram, David R Jacobs, Maryam Kavousi, Chiea Chuen Khor, Tuomas O Kilpeläinen, Woon-Puay Koh, Pirjo Komulainen, Carl D Langefeld, Jingjing Liang, Kiang Liu, Jianjun Liu, Kurt Lohman, Reedik Mägi, Ani W Manichaikul, Colin A Mckenzie, Thomas Meitinger, Yuri Milaneschi, Matthias Nauck, Christopher P Nelson, Jeffrey R O'Connell, Nicholette D Palmer, Alexandre C Pereira, Thomas Perls, Annette Peters, Ozren Polašek, Olli T Raitakari, Kenneth Rice, Treva K Rice, Stephen S Rich, Charumathi Sabanayagam, Pamela J Schreiner, Xiao-Ou Shu, Stephen Sidney, Mario Sims, Jennifer A Smith, John M Starr, Konstantin Strauch, E Shyong Tai, Kent D Taylor, Michael Y Tsai, André G Uitterlinden, Diana Van Heemst, Melanie Waldenberger, Ya-Xing Wang, Wen-Bin Wei, Gregory Wilson, Deng Xuan, Jie Yao, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Diane M Becker, Amélie Bonnefond, Donald W Bowden, Richard S Cooper, Ian J Deary, Jasmin Divers, Tõnu Esko, Paul W Franks, Philippe Froguel, Christian Gieger, Jost B Jonas, Norihiro Kato, Timo A Lakka, Karin Leander, Terho Lehtimäki, Patrik K E Magnusson, Kari E North, Ioanna Ntalla, Brenda Penninx, Nilesh J Samani, Harold Snieder, Beatrice Spedicati, Pim Van Der Harst, Henry Völzke, Lynne E Wagenknecht, David R Weir, Mary K Wojczynski, Tangchun Wu, Wei Zheng, Xiaofeng Zhu, Claude Bouchard, Daniel I Chasman, Michele K Evans, Ervin R Fox, Vilmundur Gudnason, Caroline Hayward, Bernardo L Horta, Sharon L R Kardia, Jose Eduardo Krieger, Dennis O Mook-Kanamori, Patricia A Peyser, Michael M Province, Bruce M Psaty, Igor Rudan, Xueling Sim, Blair H Smith, Rob M Van Dam, Cornelia M Van Duijn, Tien Yin Wong, Donna K Arnett, Dabeeru C Rao, James Gauderman, Ching-Ti Liu, Alanna C Morrison, Jerome I Rotter, Myriam Fornage

Journal Articles

No abstract provided.

Whole Genome Sequencing Identifies Structural Variants Contributing To Hematologic Traits In The Nhlbi Topmed Program, Marsha M Wheeler, Adrienne M Stilp, Shuquan Rao, Bjarni V Halldórsson, Doruk Beyter, Jia Wen, Anna V Mihkaylova, Caitlin P Mchugh, John Lane, Min-Zhi Jiang, Laura M Raffield, Goo Jun, Fritz J Sedlazeck, Ginger Metcalf, Yao Yao, Joshua B Bis, Nathalie Chami, Paul S De Vries, Pinkal Desai, James S Floyd, Yan Gao, Kai Kammers, Wonji Kim, Jee-Young Moon, Aakrosh Ratan, Lisa R Yanek, Laura Almasy, Lewis C Becker, John Blangero, Michael H Cho, Joanne E Curran, Myriam Fornage, Robert C Kaplan, Joshua P Lewis, Ruth J F Loos, Braxton D Mitchell, Alanna C Morrison, Michael Preuss, Bruce M Psaty, Stephen S Rich, Jerome I Rotter, Hua Tang, Russell P Tracy, Eric Boerwinkle, Goncalo R Abecasis, Thomas W Blackwell, Albert V Smith, Andrew D Johnson, Rasika A Mathias, Deborah A Nickerson, Matthew P Conomos, Yun Li, Unnur Þorsteinsdóttir, Magnús K Magnússon, Kari Stefansson, Nathan D Pankratz, Daniel E Bauer, Paul L Auer, Alex P Reiner

Journal Articles

Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative traits …