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Articles by Brian E. Cade
Genome-wide association analysis of composite sleep health scores in 413,904 individuals - Communications Biology
Abstract Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains.
Tailoring Risk Prediction Models to Local Populations
Key Points Question Can established cardiovascular risk tools be adapted for local populations without sacrificing interpretability? Findings This cohort study including 95 326 individuals applied a machine learning recalibration method that uses minimal variables to the American Heart Association’s Predicting Risk of Cardiovascular Disease Events (AHA-PREVENT) equations for a New England population.
"Leveraging pleiotropy to discover and interpret GWAS results for sleep" by Sung Chun, Sebastian Akle et al.
Abstract Genetic association studies of many heritable traits resulting from physiological testing often have modest sample sizes due to the cost and burden of the required phenotyping. This reduces statistical power and limits discovery of multiple genetic associations. We present a strategy to leverage pleiotropy between traits to both discover new loci and to provide mechanistic hypotheses of the underlying pathophysiology.
"Whole-genome association analyses of sleep-disordered breathing phenot" by Brian E Cade, Jiwon Lee et al.
BACKGROUND: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. METHODS: The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals.
The Ethical Beauty Advocate in Haus Labs' Empowering Campaign
Actress Gigi Dia has stepped into the world of ethical beauty with a powerful statement as part of Lady Gaga's revolutionary cosmetic brand, Haus Labs. Embracing a vegan and cruelty-free approach to beauty, Haus Labs has redefined the industry, and Gigi's partnership showcases her commitment to inclusivity and empowerment. Founded by the iconic Lady Gaga, Haus Labs is more than just a beauty brand; it's a celebration of individuality and self-expression through makeup and body art.
Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis - Nature
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Abstract Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2,3,4,5,6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling.
By Joshua Weinstock, Bala Bharathi Burugula, Mesbah Uddin, Bence Daniel, Shaneice Mitchell, Cecelia Laurie, Joshua Lewis, Kathleen C. Barnes, Myriam Fornage, Susan Redline, Brian E. Cade, Bruce M. Psaty, Joshua C. Bis, Jennifer Brody, Nicholette D. Palmer, Michael Cho, Ramachandran S. Vasan, Lisa R. Yanek, Patricia A. Peyser, Michiel Rienstra, Susan R. Heckbert, Nicholas Smith, Kerri L. Wiggins, Michael Cutler, Stacey Knight, Adolfo Correa, Stephen S. Rich, Peter M Nilsson, Brian Custer, Joanne Curran, John Blangero, Stephen T. McGarvey, Gregory M Marcus, Dawood Darbar, Charles Kooperberg, Andrew Johnson, Rasika A. Mathias, NHLBI Trans-Omics, Albert Smith, Ansuman T. Satpathy, Pradeep Natarajan, Jacob O. Kitzman, Eric A. Whitsel, Alexander Bick, Jayakrishnan Gopakumar, Taralynn M. Mack, Clive R. Pullinger
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Nature
Verified
An integrated multi-omics analysis of sleep-disordered breathing traits implicates P2XR4 purinergic signaling - Communications Biology
Abstract Sleep Disordered Breathing (SDB) is a common disease associated with increased risk for cardiometabolic, cardiovascular, and cognitive diseases. How SDB affects the molecular environment is still poorly understood. We study the association of three SDB measures with gene expression measured using RNA-seq in multiple blood tissues from the Multi-Ethnic Study of Atherosclerosis.
Leveraging pleiotropy to discover and interpret GWAS results for sleep-associated traits
Simulations We first used simulations to assess our strategy to identify true associations in an underpowered study by detecting pleiotropic associations with a better-powered study of another trait and following up with replication in an independent cohort. To assess sensitivity and specificity, we simulated variable proportions of shared and distinct causal effects, whilst assuming high polygenicity for each trait and only one causative variant per locus.
Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies - Nature Genetics
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Abstract Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies.
By Xihao Li, Corbin Quick, Sheila M. Gaynor, Margaret Sunitha Selvaraj, Rounak Dey, Donna Arnett, Lawrence F. Bielak, John Blangero, Jennifer Brody, Brian E. Cade, L. Cupples, Joanne Curran, Barry I. Freedman, Xiuqing Guo, Charles Kooperberg, Brian G. Kral, Lisa Martin, Stephen T. McGarvey, May E. Montasser, Alanna C. Morrison, Nicholette D. Palmer, Kenneth Rice, Stephen S. Rich, Ramachandran S. Vasan, Cristen J. Willer, Lisa R. Yanek, Wei Zhao, NHLBI Trans-Omics, Gina M. Peloso, Zilin Li, Jennifer Smith
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Nature
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Whole genome sequence analysis of blood lipid levels in >66,000 individuals - Nature Communications
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Abstract Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance.
By Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Akhil Pampana, David Zhang, Joseph Park, Joshua C. Bis, Jennifer Brody, Brian E. Cade, Lee-Ming Chuang, Ren-Hua Chung, Joanne Curran, Barry I. Freedman, Mariaelisa Graff, Xiuqing Guo, Nancy L. Heard-Costa, Chii-Min Hwu, Steven A. Lubitz, May E. Montasser, Alanna C. Morrison, Nicholette D. Palmer, Patricia A. Peyser, Xiao Sun, Zhe Wang, Yuxuan Wang, Lisa R. Yanek, Wei Zhao, Donna Arnett, John Blangero, L. Cupples, Susan K. Dutcher, Patrick T. Ellinor, Myriam Fornage, Charles Kooperberg, Rasika A. Mathias, Stephen T. McGarvey, Bruce M. Psaty, Ramachandran S. Vasan, Stephen S. Rich, Cristen J. Willer, Daniel Rader, Xihong Lin, NHLBI Trans-Omics, Gina M. Peloso, Brian G. Kral, Martin Lisa, Preuss Michael, Soren Germer, Jennifer Smith
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Nature
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Associations of sleep duration and sleep-wake rhythm with lung parenchymal abnormalities on computed tomography: The MESA study
RESEARCH ARTICLE John S. Kim, Corresponding Author jk6jb@hscmail.mcc.virginia.edu orcid.org/0000-0002-8887-150X Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA Correspondence John S. Kim, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, PO Box 800546, Charlottesville, VA 22908-0546, USA.
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