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201. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 2020

Author

Tenforde, Mark W, Kim, Sara S, Lindsell, Christopher J, Billig Rose, Erica, Shapiro, Nathan I, Files, D Clark, Gibbs, Kevin W, Erickson, Heidi L, Steingrub, Jay S, Smithline, Howard A, Gong, Michelle N, Aboodi, Michael S, Exline, Matthew C, Henning, Daniel J, Wilson, Jennifer G, Khan, Akram, Qadir, Nida, Brown, Samuel M, Peltan, Ithan D, Rice, Todd W, Hager, David N, Ginde, Adit A, Stubblefield, William B, Patel, Manish M, Self, Wesley H, Feldstein, Leora R, Hart, Kimberly W, McClellan, Robert, Dorough, Layne, Dzuris, Nicole, Griggs, Eric P, Kassem, Ahmed M, Marcet, Paula L, Ogokeh, Constance E, Sciarratta, Courtney N, Siddula, Akshita, Smith, Emily R, and Wu, Michael J

Subjects
Brain Disorders, Prevention, Behavioral and Social Science, Clinical Research, Lung, Good Health and Well Being, Adolescent, Adult, Ambulatory Care, COVID-19, Coronavirus Infections, Delivery of Health Care, Female, Humans, Male, Middle Aged, Pandemics, Pneumonia, Viral, Recovery of Function, Risk Factors, Time Factors, Treatment Outcome, United States, Young Adult, IVY Network Investigators, CDC COVID-19 Response Team, IVY Network Investigators, General & Internal Medicine
Abstract

Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.

Published
2020

202. Machine Learning Characterization of COPD Subtypes Insights From the COPDGene Study

Author

Castaldi, Peter J, Boueiz, Adel, Yun, Jeong, San Jose Estepar, Raul, Ross, James C, Washko, George, Cho, Michael H, Hersh, Craig P, Kinney, Gregory L, Young, Kendra A, Regan, Elizabeth A, Lynch, David A, Criner, Gerald J, Dy, Jennifer G, Rennard, Stephen I, Casaburi, Richard, Make, Barry J, Crapo, James, Silverman, Edwin K, Hokanson, John E, Crapo, James D, Beaty, Terri, Begum, Ferdouse, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hetmanski, Jacqueline, Hobbs, Brian D, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Prokopenko, Dmitry, Qiao, Dandi, Regan, Elizabeth, Sakornsakolpat, Phuwanat, Wan, Emily S, Won, Sungho, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O, Galban, Craig J, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Nardelli, Pietro, Newell, John D, Notary, Aleena, Oh, Andrea, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Kinney, Gregory, Bhatt, Surya P, Bon, Jessica, Diaz, Alejandro A, Make, Barry, Murray, Susan, Soler, Xavier, Bowler, Russell P, and Kechris, Katerina

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Lung, 2.1 Biological and endogenous factors, Aetiology, Respiratory, Cluster Analysis, Diagnostic Imaging, Disease Progression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Machine Learning, Molecular Epidemiology, Phenotype, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, COPD, emphysema, machine learning, COPDGene Investigators, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.

Published
2020

203. Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Author

Zekavat, Seyedeh M, Ruotsalainen, Sanni, Handsaker, Robert E, Alver, Maris, Bloom, Jonathan, Poterba, Timothy, Seed, Cotton, Ernst, Jason, Chaffin, Mark, Engreitz, Jesse, Peloso, Gina M, Manichaikul, Ani, Yang, Chaojie, Ryan, Kathleen A, Fu, Mao, Johnson, W Craig, Tsai, Michael, Budoff, Matthew, Vasan, Ramachandran S, Cupples, L Adrienne, Rotter, Jerome I, Rich, Stephen S, Post, Wendy, Mitchell, Braxton D, Correa, Adolfo, Metspalu, Andres, Wilson, James G, Salomaa, Veikko, Kellis, Manolis, Daly, Mark J, Neale, Benjamin M, McCarroll, Steven, Surakka, Ida, Esko, Tonu, Ganna, Andrea, Ripatti, Samuli, Kathiresan, Sekar, Natarajan, Pradeep, and NHLBI TOPMed Lipids Working Group

Subjects
NHLBI TOPMed Lipids Working Group
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

204. De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population

Author

Kessler, Michael D, Loesch, Douglas P, Perry, James A, Heard-Costa, Nancy L, Taliun, Daniel, Cade, Brian E, Wang, Heming, Daya, Michelle, Ziniti, John, Datta, Soma, Celedón, Juan C, Soto-Quiros, Manuel E, Avila, Lydiana, Weiss, Scott T, Barnes, Kathleen, Redline, Susan S, Vasan, Ramachandran S, Johnson, Andrew D, Mathias, Rasika A, Hernandez, Ryan, Wilson, James G, Nickerson, Deborah A, Abecasis, Goncalo, Browning, Sharon R, Zöllner, Sebastian, O’Connell, Jeffrey R, Mitchell, Braxton D, Lung, and Blood Institute Trans-Omics for Precision Medicine Consortium National Heart, Group, TOPMed Population Genetics Working, O’Connor, Timothy D, Aalbers, Sanne, Abdalla, Moustafa, Abdul-Rahman, Omar, Abecasis, Gonçalo, Abhyankar, Avinash, Adrianto, Indra, Aguet, Francois, Akers, Rachel, Al-Tobasei, Rafet, Albert, Christine, Aldred, Micheala, Almasy, Laura, Almeida, Marcio, Alonso, Alvaro, Ament, Seth, Ampleford, Elizabeth, An, Ping, Anderson, Christopher D, Andersson, Charlotte, Anugu, Pramod, Appelbaum, Elizabeth, Ardlie, Kristin, Arking, Dan, Armasu, Sebastian M, Arnett, Donna K, Arruda, Heather, Arvanitis, Marios, Ashley-Koch, Allison, Ashrani, Aneel, Aslibekyan, Stella, Assimes, Tim, Atkinson, Elizabeth, Auer, Paul, Austin, Thomas R, Avery, Christy, Avila-Pacheco, Julian, Avillach, Paul, Aviv, Abraham, Avramopoulos, Dimitrios, Ballantyne, Christie, Balte, Pallavi, Bamshad, Michael, Bancks, Mike, Barnard, John, Barr, R Graham, Barron-Casella, Emily, Bartz, Traci, Barwick, Lucas, Basu, Saonli, Battle, Alexis, Baumann, Michael, Beame, David, Beaty, Terri, Beck, Gerald, Becker, Lewis, Becker, Diane, Beer, Rebecca, Begum, Ferdouse, Beiser, Alexa, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Berk-Rauch, Hanna, Besich, Zachary M, Bezerra, Marcos, Bhatt, Surya, Bi, Wenjian, Bick, Alexander, and Bielak, Larry

Subjects
Biological Sciences, Genetics, Human Genome, Good Health and Well Being, Adult, Amish, Cohort Studies, DNA Mutational Analysis, Female, Genetics, Population, Genome, Human, Heterozygote, Humans, Male, Mutation, Pedigree, Whole Genome Sequencing, Young Adult, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Population Genetics Working Group, de novo mutations, diversity, mutation rate, recombination
Abstract

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains

Published
2020

205. Disease Progression Modeling in Chronic Obstructive Pulmonary Disease

Author

Young, Alexandra L, Bragman, Felix JS, Rangelov, Bojidar, Han, MeiLan K, Galbán, Craig J, Lynch, David A, Hawkes, David J, Alexander, Daniel C, Hurst, John R, Crapo, James D, Silverman, Edwin K, Make, Barry J, Regan, Elizabeth A, Beaty, Terri, Begum, Ferdouse, Castaldi, Peter J, Cho, Michael, DeMeo, Dawn L, Boueiz, Adel R, Foreman, Marilyn G, Halper-Stromberg, Eitan, Hayden, Lystra P, Hersh, Craig P, Hetmanski, Jacqueline, Hobbs, Brian D, Hokanson, John E, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Parker, Margaret M, Qiao, Dandi, Wan, Emily S, Won, Sungho, Sakornsakolpat, Phuwanat, Prokopenko, Dmitry, Al Qaisi, Mustafa, Coxson, Harvey O, Gray, Teresa, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Newell, John D, Ross, James C, Estepar, Raul San Jose, Schroeder, Joyce, Sieren, Jered, Stinson, Douglas, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Washko, George, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Moore, Camille, Strand, Matt, Hughes, John, Kinney, Gregory, Pratte, Katherine, Young, Kendra A, Bhatt, Surya, Bon, Jessica, Martinez, Carlos, Murray, Susan, Soler, Xavier, Bowler, Russell P, Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L, Martinez, Carlos H, Pernicano, Perry G, Hanania, Nicola, Alapat, Philip, Atik, Mustafa, Bandi, Venkata, Boriek, Aladin, Guntupalli, Kalpatha, Guy, Elizabeth, Nachiappan, Arun, Parulekar, Amit, Barr, R Graham, Austin, John, D’Souza, Belinda, Pearson, Gregory DN, Rozenshtein, Anna, Thomashow, Byron, MacIntyre, Neil, McAdams, H Page, Washington, Lacey, McEvoy, Charlene, and Tashjian, Joseph

Subjects
Biomedical Imaging, Lung, Clinical Research, Chronic Obstructive Pulmonary Disease, Aetiology, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Respiratory, Aged, Disease Progression, Female, Humans, Male, Middle Aged, Models, Theoretical, Pulmonary Disease, Chronic Obstructive, Tomography, X-Ray Computed, clustering, CT imaging, emphysema, bronchitis, chronic obstructive pulmonary disease, COPDGene Investigators, Medical and Health Sciences, Respiratory System
Abstract

Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue→Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway→Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P

Published
2020

206. Smoking-by-genotype interaction in type 2 diabetes risk and fasting glucose

Author

Wu, Peitao, Rybin, Denis, Bielak, Lawrence F, Feitosa, Mary F, Franceschini, Nora, Li, Yize, Lu, Yingchang, Marten, Jonathan, Musani, Solomon K, Noordam, Raymond, Raghavan, Sridharan, Rose, Lynda M, Schwander, Karen, Smith, Albert V, Tajuddin, Salman M, Vojinovic, Dina, Amin, Najaf, Arnett, Donna K, Bottinger, Erwin P, Demirkan, Ayse, Florez, Jose C, Ghanbari, Mohsen, Harris, Tamara B, Launer, Lenore J, Liu, Jingmin, Liu, Jun, Mook-Kanamori, Dennis O, Murray, Alison D, Nalls, Mike A, Peyser, Patricia A, Uitterlinden, André G, Voortman, Trudy, Bouchard, Claude, Chasman, Daniel, Correa, Adolfo, de Mutsert, Renée, Evans, Michele K, Gudnason, Vilmundur, Hayward, Caroline, Kao, Linda, Kardia, Sharon LR, Kooperberg, Charles, Loos, Ruth JF, Province, Michael M, Rankinen, Tuomo, Redline, Susan, Ridker, Paul M, Rotter, Jerome I, Siscovick, David, Smith, Blair H, van Duijn, Cornelia, Zonderman, Alan B, Rao, DC, Wilson, James G, Dupuis, Josée, Meigs, James B, Liu, Ching-Ti, and Vassy, Jason L

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Pharmacology and Pharmaceutical Sciences, Tobacco, Aging, Tobacco Smoke and Health, Human Genome, Nutrition, Diabetes, Clinical Research, Prevention, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Aged, Black People, Blood Glucose, Cigarette Smoking, Cohort Studies, Diabetes Mellitus, Type 2, Fasting, Feasibility Studies, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, White People, General Science & Technology
Abstract

Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. never) on incident T2D and fasting glucose (FG). Analyses were performed in participants of European (EA) and African ancestry (AA) separately. Discovery analyses were conducted using genotype data from the 50,000-single-nucleotide polymorphism (SNP) ITMAT-Broad-CARe (IBC) array in 5 cohorts from from the Candidate Gene Association Resource Consortium (n = 23,189). Replication was performed in up to 16 studies from the Cohorts for Heart Aging Research in Genomic Epidemiology Consortium (n = 74,584). In meta-analysis of discovery and replication estimates, 5 SNPs met at least one criterion for potential interaction with smoking on incident T2D at p

Published
2020

207. Characteristics of Adult Outpatients and Inpatients with COVID-19 — 11 Academic Medical Centers, United States, March–May 2020

Author

Tenforde, Mark W, Billig Rose, Erica, Lindsell, Christopher J, Shapiro, Nathan I, Files, D Clark, Gibbs, Kevin W, Prekker, Matthew E, Steingrub, Jay S, Smithline, Howard A, Gong, Michelle N, Aboodi, Michael S, Exline, Matthew C, Henning, Daniel J, Wilson, Jennifer G, Khan, Akram, Qadir, Nida, Stubblefield, William B, Patel, Manish M, Self, Wesley H, Feldstein, Leora R, Kassem, Ahmed M, Sciarratta, Courtney N, Dzuris, Nicole, Marcet, Paula L, Siddula, Akshita, Griggs, Eric P, Smith, Emily R, Ogokeh, Constance E, Wu, Michael, and Kim, Sara S

Subjects
Lung, Infectious Diseases, Prevention, Emerging Infectious Diseases, Clinical Research, Infection, Good Health and Well Being, Academic Medical Centers, Adult, Aged, COVID-19, Coronavirus Infections, Female, Humans, Inpatients, Male, Middle Aged, Outpatients, Pandemics, Pneumonia, Viral, Risk Factors, Socioeconomic Factors, United States, CDC COVID-19 Response Team, General & Internal Medicine
Abstract

Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3).

Published
2020

208. Neuromodulated Learning in Deep Neural Networks

Author

Wilson, Dennis G, Cussat-Blanc, Sylvain, Luga, Hervé, and Harrington, Kyle

Subjects
Computer Science - Neural and Evolutionary Computing, Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

In the brain, learning signals change over time and synaptic location, and are applied based on the learning history at the synapse, in the complex process of neuromodulation. Learning in artificial neural networks, on the other hand, is shaped by hyper-parameters set before learning starts, which remain static throughout learning, and which are uniform for the entire network. In this work, we propose a method of deep artificial neuromodulation which applies the concepts of biological neuromodulation to stochastic gradient descent. Evolved neuromodulatory dynamics modify learning parameters at each layer in a deep neural network over the course of the network's training. We show that the same neuromodulatory dynamics can be applied to different models and can scale to new problems not encountered during evolution. Finally, we examine the evolved neuromodulation, showing that evolution found dynamic, location-specific learning strategies.

Published
2018

209. Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations.

Author

Kowalski, Madeline H, Qian, Huijun, Hou, Ziyi, Rosen, Jonathan D, Tapia, Amanda L, Shan, Yue, Jain, Deepti, Argos, Maria, Arnett, Donna K, Avery, Christy, Barnes, Kathleen C, Becker, Lewis C, Bien, Stephanie A, Bis, Joshua C, Blangero, John, Boerwinkle, Eric, Bowden, Donald W, Buyske, Steve, Cai, Jianwen, Cho, Michael H, Choi, Seung Hoan, Choquet, Hélène, Cupples, L Adrienne, Cushman, Mary, Daya, Michelle, de Vries, Paul S, Ellinor, Patrick T, Faraday, Nauder, Fornage, Myriam, Gabriel, Stacey, Ganesh, Santhi K, Graff, Misa, Gupta, Namrata, He, Jiang, Heckbert, Susan R, Hidalgo, Bertha, Hodonsky, Chani J, Irvin, Marguerite R, Johnson, Andrew D, Jorgenson, Eric, Kaplan, Robert, Kardia, Sharon LR, Kelly, Tanika N, Kooperberg, Charles, Lasky-Su, Jessica A, Loos, Ruth JF, Lubitz, Steven A, Mathias, Rasika A, McHugh, Caitlin P, Montgomery, Courtney, Moon, Jee-Young, Morrison, Alanna C, Palmer, Nicholette D, Pankratz, Nathan, Papanicolaou, George J, Peralta, Juan M, Peyser, Patricia A, Rich, Stephen S, Rotter, Jerome I, Silverman, Edwin K, Smith, Jennifer A, Smith, Nicholas L, Taylor, Kent D, Thornton, Timothy A, Tiwari, Hemant K, Tracy, Russell P, Wang, Tao, Weiss, Scott T, Weng, Lu-Chen, Wiggins, Kerri L, Wilson, James G, Yanek, Lisa R, Zöllner, Sebastian, North, Kari E, Auer, Paul L, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology & Hemostasis Working Group, Raffield, Laura M, Reiner, Alexander P, and Li, Yun

Subjects
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology & Hemostasis Working Group, Humans, Genetic Predisposition to Disease, Computational Biology, Genetics, Population, Gene Frequency, Linkage Disequilibrium, Databases, Genetic, Adult, Aged, Aged, 80 and over, Middle Aged, African Americans, Hispanic Americans, United States, Female, Male, Genome-Wide Association Study, beta-Globins, Genotyping Techniques, Precision Medicine, Whole Genome Sequencing, Genetics, Population, Databases, Genetic, and over, Developmental Biology
Abstract

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) < 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11-34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count 86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8x10-15] in African populations, rs11549407 with lower HGB [p = 1.5x10-12] and HCT [p = 8.8x10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations.

Published
2019

210. Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans

Author

Guan, Meijian, Keaton, Jacob M, Dimitrov, Latchezar, Hicks, Pamela J, Xu, Jianzhao, Palmer, Nicholette D, Ma, Lijun, Das, Swapan K, Chen, Yii-Der I, Coresh, Josef, Fornage, Myriam, Franceschini, Nora, Kramer, Holly, Langefeld, Carl D, Mychaleckyj, Josyf C, Parekh, Rulan S, Post, Wendy S, Rasmussen-Torvik, Laura J, Rich, Stephen S, Rotter, Jerome I, Sedor, John R, Thornley-Brown, Denyse, Tin, Adrienne, Wilson, James G, Freedman, Barry I, Bowden, Donald W, and Ng, Maggie CY

Subjects
Biological Sciences, Genetics, Human Genome, Diabetes, Prevention, Kidney Disease, 2.1 Biological and endogenous factors, Aetiology, Renal and urogenital, Metabolic and endocrine, Good Health and Well Being, African Americans, Genome-wide association study, Type 2 diabetes, Diabetic kidney disease, End-stage kidney disease, FIND Consortium, Genetics & Heredity, Biochemistry and cell biology
Abstract

BackgroundEnd-stage kidney disease (ESKD) is a significant public health concern disproportionately affecting African Americans (AAs). Type 2 diabetes (T2D) is the leading cause of ESKD in the USA, and efforts to uncover genetic susceptibility to diabetic kidney disease (DKD) have had limited success. A prior genome-wide association study (GWAS) in AAs with T2D-ESKD was expanded with additional AA cases and controls and genotypes imputed to the higher density 1000 Genomes reference panel. The discovery analysis included 3432 T2D-ESKD cases and 6977 non-diabetic non-nephropathy controls (N = 10,409), followed by a discrimination analysis in 2756 T2D non-nephropathy controls to exclude T2D-associated variants.ResultsSix independent variants located in or near RND3/RBM43, SLITRK3, ENPP7, GNG7, and APOL1 achieved genome-wide significant association (P

Published
2019

211. Sexuality Education for Primary School Students with Disability in Fiji

Author

Botfield, Jessica R., Ratu, Sera, Turagabeci, Esiteri, Chivers, Jane, McDonald, Loren, Wilson, Eleanor G., and Cheng, Yan

Abstract

Background: People with disability have the same sexual and reproductive health needs and rights as people without disability, yet experience considerable barriers in accessing information and services. The Reproductive and Family Health Association of Fiji, Family Planning Australia, and disability stakeholders implemented a comprehensive sexuality education (CSE) disability inclusion project to increase access for students with disability to age-appropriate sexuality education. Method: A train the trainer model was utilised, whereby staff and disability stakeholders undertook competency-based training on delivering sexuality education to teachers and people with disability, then trained and supported teachers working in special disability schools to provide sexuality education to students. An evaluation explored the acceptability and effectiveness of the project, utilising baseline and endline surveys and interviews. Findings: From 2016 to 2018, the CSE disability project reached teachers and students in nine special disability schools in Fiji. At project completion, teachers reported increased confidence overall in teaching about sexuality and relationships, and students demonstrated increased knowledge regarding puberty and body changes. Interview findings suggested the project contributed to overcoming silence and stigma for people with disability and promoting safety for young people. Conclusion: Age- and developmentally appropriate sexuality education for people with disability is essential for equipping them with necessary knowledge and skills. The CSE disability project utilised a collaborative, capacity building approach to co-design and implement sexuality education in special disability schools in Fiji. With commitment from stakeholders, this could be sustained and expanded to support students with disability in achieving optimal sexual and reproductive health.

Published
2021
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212. Microaggressions: How They Are Committed and Contained

Author

Wilson, Priscilla G.

Abstract

The term microaggression is defined and demonstrated from the viewpoint of graduate-level students. Using a classroom assignment, the students describe their personal experiences of being the recipient of a microaggression. The students describe the type of microaggression, theme, psychological dilemma, and recall how they reacted to the encounter. The physical and psychological impact of microaggressions on diverse populations is explained to provide insight on the outcomes. Implications are discussed as well as how the counselor or helping professional can use the client's experience as a tool for empowerment.

Published
2017

213. Dodonaea viscosa Jacq. induces cytotoxicity, antiproliferative activity, and cell death in colorectal cancer cells via regulation of caspase 3 and p53

Author

Oscar Herrera-Calderon, Angie Herrera-Ramírez, Wilson Cardona-G, Elizabeth Julia Melgar-Merino, Haydee Chávez, Josefa Bertha Pari-Olarte, Eddie Loyola-Gonzales, José Francisco Kong-Chirinos, José Santiago Almeida-Galindo, Gilmar Peña-Rojas, and Vidalina Andía-Ayme

Subjects
Dodonaea viscosa, medicinal plant, colorectal cancer, phytochemical screening, cell death, Therapeutics. Pharmacology, RM1-950
Abstract

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is the second leading cause of cancer-related death due to an insufficiency prognosis and is generally diagnosed in the last step of development. The Peruvian flora has a wide variety of medicinal plants with therapeutic potential in several diseases. Dodonaea viscosa Jacq. is a plant used to treat inflammatory process as well as gastrointestinal diseases. The aim of this study was to examine the cytotoxic, antiproliferative, and cell death-inducing effects of D. viscosa on colorectal cancer cells (SW480 and SW620). The hydroethanolic extract was obtained by maceration at 70% ethanol, the phytochemical constituents were identified by LC-ESI-MS. D. viscosa revealed 57 compounds some of them are: isorhamnetin, kaempferol, quercetin, methyl dodovisate B, hardwickiic acid, viscosol, and dodonic acid. Regarding the antitumoral activity, D. viscosa induced cytotoxic and antiproliferative activity in both SW480 and SW620 cancer cells, accompanied with, important changes in mitochondrial membrane potential, formation of the Sub G0/G1 population and increasing levels of apoptotic biomarkers (caspase 3 and the tumor suppressor protein p53) in the metastatic derivative cell line (SW620), suggesting an intrinsic apoptotic process after the treatment with the hydroethanolic extract of D. viscosa.

Published
2023
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219. Dust Production and Depletion in Evolved Planetary Systems

Author

Farihi, J., van Lieshout, R., Cauley, P. W., Dennihy, E., Su, K. Y. L., Kenyon, S. J., Wilson, T. G., Toloza, O., Gänsicke, B. T., von Hippel, T., Redfield, S., Debes, J. H., Xu, S., Rogers, L., Bonsor, A., Swan, A., Pala, A. F., and Reach, W. T.

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Solar and Stellar Astrophysics
Abstract

The infrared dust emission from the white dwarf GD 56 is found to rise and fall by 20% peak-to-peak over 11.2 yr, and is consistent with ongoing dust production and depletion. It is hypothesized that the dust is produced via collisions associated with an evolving dust disk, temporarily increasing the emitting surface of warm debris, and is subsequently destroyed or assimilated within a few years. The variations are consistent with debris that does not change temperature, indicating that dust is produced and depleted within a fixed range of orbital radii. Gas produced in collisions may rapidly re-condense onto grains, or may accrete onto the white dwarf surface on viscous timescales that are considerably longer than Poynting-Robertson drag for micron-sized dust. This potential delay in mass accretion rate change is consistent with multi-epoch spectra of the unchanging Ca II and Mg II absorption features in GD 56 over 15 yr, although the sampling is sparse. Overall these results indicate that collisions are likely to be the source of dust and gas, either inferred or observed, orbiting most or all polluted white dwarfs., Comment: 11 pages, 6 figures, and 2 tables. Accepted to MNRAS

Published
2018
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220. Infrared Variability of Two Dusty White Dwarfs

Author

Xu, Siyi, Su, Kate Y. L., Rogers, Laura, Bonsor, Amy, Olofsson, Johan, Veras, Dimitri, van Lieshout, Rik, Dufour, Patrick, Green, Elizabeth M., Schlawin, Everett, Farihi, Jay, Wilson, Thomas G., Wilson, David J., and Gaensicke, B T.

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Solar and Stellar Astrophysics
Abstract

The most heavily polluted white dwarfs often show excess infrared radiation from circumstellar dust disks, which are modeled as a result of tidal disruption of extrasolar minor planets. Interaction of dust, gas, and disintegrating objects can all contribute to the dynamical evolution of these dust disks. Here, we report on two infrared variable dusty white dwarfs, SDSS J1228+1040 and G29-38. For SDSS J1228+1040, compared to the first measurements in 2007, the IRAC [3.6] and [4.5] fluxes decreased by 20% by 2014 to a level also seen in the recent 2018 observations. For G29-38, the infrared flux of the 10 $\mu$m silicate emission feature became 10% stronger between 2004 and 2007, We explore several scenarios that could account for these changes, including tidal disruption events, perturbation from a companion, and runaway accretion. No satisfactory causes are found for the flux drop in SDSS J1228+1040 due to the limited time coverage. Continuous tidal disruption of small planetesimals could increase the mass of small grains and concurrently change the strength of the 10 $\mu$m feature of G29-38. Dust disks around white dwarfs are actively evolving and we speculate that there could be different mechanisms responsible for the temporal changes of these disks., Comment: ApJ, in press

Published
2018
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221. Evolving Differentiable Gene Regulatory Networks

Author

Wilson, Dennis G, Harrington, Kyle, Cussat-Blanc, Sylvain, and Luga, Hervé

Subjects
Computer Science - Neural and Evolutionary Computing
Abstract

Over the past twenty years, artificial Gene Regulatory Networks (GRNs) have shown their capacity to solve real-world problems in various domains such as agent control, signal processing and artificial life experiments. They have also benefited from new evolutionary approaches and improvements to dynamic which have increased their optimization efficiency. In this paper, we present an additional step toward their usability in machine learning applications. We detail an GPU-based implementation of differentiable GRNs, allowing for local optimization of GRN architectures with stochastic gradient descent (SGD). Using a standard machine learning dataset, we evaluate the ways in which evolution and SGD can be combined to further GRN optimization. We compare these approaches with neural network models trained by SGD and with support vector machines.

Published
2018

222. Dwarf carbon stars are likely metal-poor binaries and unlikely hosts to carbon planets

Author

Whitehouse, Lewis J., Farihi, J., Green, P. J., Wilson, T. G., and Subasavage, J. P.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Earth and Planetary Astrophysics
Abstract

Dwarf carbon stars make up the largest fraction of carbon stars in the Galaxy with around 1200 candidates known to date primarily from the Sloan Digital Sky Survey. They either possess primordial carbon-enhancements, or are polluted by mass transfer from an evolved companion such that C/O is enhanced beyond unity. To directly test the binary hypothesis, a radial velocity monitoring survey has been carried out on 28 dwarf carbon stars, resulting in the detection of variations in 21 targets. Using Monte Carlo simulations, this detection fraction is found to be consistent with a 100% binary population and orbital periods on the order of hundreds of days. This result supports the post-mass transfer nature of dwarf carbon stars, and implies they are not likely hosts to carbon planets., Comment: 5 pages, 1 figure, accepted to MNRAS

Published
2018
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223. Evolving simple programs for playing Atari games

Author

Wilson, Dennis G, Cussat-Blanc, Sylvain, Luga, Hervé, and Miller, Julian F

Subjects
Computer Science - Neural and Evolutionary Computing, Computer Science - Artificial Intelligence
Abstract

Cartesian Genetic Programming (CGP) has previously shown capabilities in image processing tasks by evolving programs with a function set specialized for computer vision. A similar approach can be applied to Atari playing. Programs are evolved using mixed type CGP with a function set suited for matrix operations, including image processing, but allowing for controller behavior to emerge. While the programs are relatively small, many controllers are competitive with state of the art methods for the Atari benchmark set and require less training time. By evaluating the programs of the best evolved individuals, simple but effective strategies can be found.

Published
2018

224. Generating Data Sets for Teaching the Importance of Regression Analysis

Author

Murray, Lori L. and Wilson, John G.

Abstract

Summary statistics and data visualizations are often used to explore data and draw preliminary conclusions. Although valuable, these tools do not always reveal the underlying patterns and trends in the data and can sometimes be misleading. We describe an approach for teaching the need for more advanced statistical analysis using multiple linear regression. Our approach is based on using a method we developed for generating alternative multivariate data sets where all the variables (both independent and dependent) have the same summary statistics. However, we can deliberately change the statistical significance of one (or more) of the independent variables in the regression to illustrate why it is important to go beyond simple descriptive measures and examine inferential statistics on the inherent relationships in the data. Implementation of this methodology is provided in the R statistical programming language and an add-in for Excel spreadsheets.

Published
2021
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225. Adipocyte JAK2 mediates spontaneous metabolic liver disease and hepatocellular carcinoma

Author

Corbit, Kevin C, Wilson, Camella G, Lowe, Dylan, Tran, Jennifer L, Vera, Nicholas B, Clasquin, Michelle, Mattis, Aras N, and Weiss, Ethan J

Subjects
Diabetes, Liver Cancer, Hepatitis, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Liver Disease, Rare Diseases, Cancer, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Metabolic and endocrine, Adipocytes, Adipose Tissue, Animals, Carcinogenesis, Carcinoma, Hepatocellular, Disease Models, Animal, Fatty Liver, Growth Hormone, Hepatocytes, Humans, Insulin Resistance, Janus Kinase 2, Liver, Liver Neoplasms, Male, Metabolic Syndrome, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease, Signal Transduction, Hepatology, Insulin, Liver cancer, Metabolism, Mouse models
Abstract

Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are liver manifestations of the metabolic syndrome and can progress to hepatocellular carcinoma (HCC). Loss of Growth Hormone (GH) signaling is reported to predispose to NAFLD and NASH through direct actions on the liver. Here, we report that aged mice lacking hepatocyte Jak2 (JAK2L), an obligate transducer of Growth Hormone (GH) signaling, spontaneously develop the full spectrum of phenotypes found in patients with metabolic liver disease, beginning with insulin resistance and lipodystrophy and manifesting as NAFLD, NASH and even HCC, independent of dietary intervention. Remarkably, insulin resistance, metabolic liver disease, and carcinogenesis are prevented in JAK2L mice via concomitant deletion of adipocyte Jak2 (JAK2LA). Further, we demonstrate that GH increases hepatic lipid burden but does so indirectly via signaling through adipocyte JAK2. Collectively, these data establish adipocytes as the mediator of GH-induced metabolic liver disease and carcinogenesis. In addition, we report a new spontaneous model of NAFLD, NASH, and HCC that recapitulates the natural sequelae of human insulin resistance-associated disease progression. The work presented here suggests a attention be paid towards inhibition of adipocyte GH signaling as a therapeutic target of metabolic liver disease.

Published
2019

226. Author Correction: Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Author

Daya, Michelle, Rafaels, Nicholas, Brunetti, Tonya M, Chavan, Sameer, Levin, Albert M, Shetty, Aniket, Gignoux, Christopher R, Boorgula, Meher Preethi, Wojcik, Genevieve, Campbell, Monica, Vergara, Candelaria, Torgerson, Dara G, Ortega, Victor E, Doumatey, Ayo, Johnston, Henry Richard, Acevedo, Nathalie, Araujo, Maria Ilma, Avila, Pedro C, Belbin, Gillian, Bleecker, Eugene, Bustamante, Carlos, Caraballo, Luis, Cruz, Alvaro, Dunston, Georgia M, Eng, Celeste, Faruque, Mezbah U, Ferguson, Trevor S, Figueiredo, Camila, Ford, Jean G, Gan, Weiniu, Gourraud, Pierre-Antoine, Hansel, Nadia N, Hernandez, Ryan D, Herrera-Paz, Edwin Francisco, Jiménez, Silvia, Kenny, Eimear E, Knight-Madden, Jennifer, Kumar, Rajesh, Lange, Leslie A, Lange, Ethan M, Lizee, Antoine, Maul, Pissamai, Maul, Trevor, Mayorga, Alvaro, Meyers, Deborah, Nicolae, Dan L, O'Connor, Timothy D, Oliveira, Ricardo Riccio, Olopade, Christopher O, Olopade, Olufunmilayo, Qin, Zhaohui S, Rotimi, Charles, Vince, Nicolas, Watson, Harold, Wilks, Rainford J, Wilson, James G, Salzberg, Steven, Ober, Carole, Burchard, Esteban G, Williams, L Keoki, Beaty, Terri H, Taub, Margaret A, Ruczinski, Ingo, Mathias, Rasika A, Barnes, Kathleen C, and CAAPA

Subjects
CAAPA
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

227. The Peak Index: Spirometry Metric for Airflow Obstruction Severity and Heterogeneity

Author

Bhatt, Surya P, Bodduluri, Sandeep, Raghav, Vrishank, Bhakta, Nirav R, Wilson, Carla G, Kim, Young-il, Eberlein, Michael, Sciurba, Frank C, Han, MeiLan K, Dransfield, Mark T, and Nakhmani, Arie

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Prevention, Clinical Trials and Supportive Activities, Lung, Chronic Obstructive Pulmonary Disease, Respiratory, Good Health and Well Being, Aged, Cross-Sectional Studies, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Multivariate Analysis, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Severity of Illness Index, Smoking, Spirometry, Surveys and Questionnaires, Survival Analysis, Tomography, X-Ray Computed, Walk Test, airflow obstruction, chronic obstructive pulmonary disease, spirometry, heterogeneity, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Spirometry loops are not smooth curves and have undulations and peaks that likely reflect heterogeneity of airflow.Objectives: To assess whether the Peak Index, the number of peaks adjusted for lung size, is associated with clinical outcomes.Methods: We analyzed spirometry data of 9,584 participants enrolled in the COPDGene study and counted the number of peaks in the descending part of the expiratory flow-volume curve from the peak expiratory flow to end-expiration. We adjusted the peaks count for the volume of the lungs from peak expiratory flow to end-expiration to derive the Peak Index. Multivariable regression analyses were performed to test associations between the Peak Index and lung function, respiratory morbidity, structural lung disease on computed tomography (CT), forced expiratory volume in 1 second (FEV1) decline, and mortality.Results: The Peak Index progressively increased from Global Initiative for Chronic Obstructive Lung Disease stage 0 through 4 (P

Published
2019

228. Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology

Author

Spracklen, Cassandra N, Karaderi, Tugce, Yaghootkar, Hanieh, Schurmann, Claudia, Fine, Rebecca S, Kutalik, Zoltan, Preuss, Michael H, Lu, Yingchang, Wittemans, Laura BL, Adair, Linda S, Allison, Matthew, Amin, Najaf, Auer, Paul L, Bartz, Traci M, Blüher, Matthias, Boehnke, Michael, Borja, Judith B, Bork-Jensen, Jette, Broer, Linda, Chasman, Daniel I, Chen, Yii-Der Ida, Chirstofidou, Paraskevi, Demirkan, Ayse, van Duijn, Cornelia M, Feitosa, Mary F, Garcia, Melissa E, Graff, Mariaelisa, Grallert, Harald, Grarup, Niels, Guo, Xiuqing, Haesser, Jeffrey, Hansen, Torben, Harris, Tamara B, Highland, Heather M, Hong, Jaeyoung, Ikram, M Arfan, Ingelsson, Erik, Jackson, Rebecca, Jousilahti, Pekka, Kähönen, Mika, Kizer, Jorge R, Kovacs, Peter, Kriebel, Jennifer, Laakso, Markku, Lange, Leslie A, Lehtimäki, Terho, Li, Jin, Li-Gao, Ruifang, Lind, Lars, Luan, Jian'an, Lyytikäinen, Leo-Pekka, MacGregor, Stuart, Mackey, David A, Mahajan, Anubha, Mangino, Massimo, Männistö, Satu, McCarthy, Mark I, McKnight, Barbara, Medina-Gomez, Carolina, Meigs, James B, Molnos, Sophie, Mook-Kanamori, Dennis, Morris, Andrew P, de Mutsert, Renee, Nalls, Mike A, Nedeljkovic, Ivana, North, Kari E, Pennell, Craig E, Pradhan, Aruna D, Province, Michael A, Raitakari, Olli T, Raulerson, Chelsea K, Reiner, Alex P, Ridker, Paul M, Ripatti, Samuli, Roberston, Neil, Rotter, Jerome I, Salomaa, Veikko, Sandoval-Zárate, America A, Sitlani, Colleen M, Spector, Tim D, Strauch, Konstantin, Stumvoll, Michael, Taylor, Kent D, Thuesen, Betina, Tönjes, Anke, Uitterlinden, Andre G, Venturini, Cristina, Walker, Mark, Wang, Carol A, Wang, Shuai, Wareham, Nicholas J, Willems, Sara M, Willems van Dijk, Ko, Wilson, James G, Wu, Ying, Yao, Jie, Young, Kristin L, Langenberg, Claudia, and Frayling, Timothy M

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Nutrition, Obesity, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Cardiovascular, Adiponectin, Adipose Tissue, Adolescent, Adult, Black or African American, Aged, Aged, 80 and over, Exome, Female, Genetic Predisposition to Disease, Hispanic or Latino, Humans, Lipids, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, White People, Young Adult, adiponectin, cardio metabolic traits, exome, genetics, genome-wide association study, lipids, obesity, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

Published
2019

229. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Author

Daya, Michelle, Rafaels, Nicholas, Brunetti, Tonya M, Chavan, Sameer, Levin, Albert M, Shetty, Aniket, Gignoux, Christopher R, Boorgula, Meher Preethi, Wojcik, Genevieve, Campbell, Monica, Vergara, Candelaria, Torgerson, Dara G, Ortega, Victor E, Doumatey, Ayo, Johnston, Henry Richard, Acevedo, Nathalie, Araujo, Maria Ilma, Avila, Pedro C, Belbin, Gillian, Bleecker, Eugene, Bustamante, Carlos, Caraballo, Luis, Cruz, Alvaro, Dunston, Georgia M, Eng, Celeste, Faruque, Mezbah U, Ferguson, Trevor S, Figueiredo, Camila, Ford, Jean G, Gan, Weiniu, Gourraud, Pierre-Antoine, Hansel, Nadia N, Hernandez, Ryan D, Herrera-Paz, Edwin Francisco, Jiménez, Silvia, Kenny, Eimear E, Knight-Madden, Jennifer, Kumar, Rajesh, Lange, Leslie A, Lange, Ethan M, Lizee, Antoine, Maul, Pissamai, Maul, Trevor, Mayorga, Alvaro, Meyers, Deborah, Nicolae, Dan L, O'Connor, Timothy D, Oliveira, Ricardo Riccio, Olopade, Christopher O, Olopade, Olufunmilayo, Qin, Zhaohui S, Rotimi, Charles, Vince, Nicolas, Watson, Harold, Wilks, Rainford J, Wilson, James G, Salzberg, Steven, Ober, Carole, Burchard, Esteban G, Williams, L Keoki, Beaty, Terri H, Taub, Margaret A, Ruczinski, Ingo, Mathias, Rasika A, Barnes, Kathleen C, and CAAPA

Subjects
CAAPA, Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 17, Humans, Asthma, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, African Americans, Hispanic Americans, United States, Genome-Wide Association Study, Genetic Loci, Chromosomes, Human, Pair 12, Pair 17, Pair 8, Polymorphism, Single Nucleotide
Abstract

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.

Published
2019

230. Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans

Author

Wang, Heming, Cade, Brian E, Sofer, Tamar, Sands, Scott A, Chen, Han, Browning, Sharon R, Stilp, Adrienne M, Louie, Tin L, Thornton, Timothy A, Johnson, W Craig, Below, Jennifer E, Conomos, Matthew P, Evans, Daniel S, Gharib, Sina A, Guo, Xiuqing, Wood, Alexis C, Mei, Hao, Yaffe, Kristine, Loredo, Jose S, Ramos, Alberto R, Barrett-Connor, Elizabeth, Ancoli-Israel, Sonia, Zee, Phyllis C, Arens, Raanan, Shah, Neomi A, Taylor, Kent D, Tranah, Gregory J, Stone, Katie L, Hanis, Craig L, Wilson, James G, Gottlieb, Daniel J, Patel, Sanjay R, Rice, Ken, Post, Wendy S, Rotter, Jerome I, Sunyaev, Shamil R, Cai, Jianwen, Lin, Xihong, Purcell, Shaun M, Laurie, Cathy C, Saxena, Richa, Redline, Susan, and Zhu, Xiaofeng

Subjects
Biological Sciences, Genetics, Sleep Research, Lung, Aged, Chromosome Mapping, Female, Ferrochelatase, Genome-Wide Association Study, Genotype, Hispanic or Latino, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Polysomnography, Sleep Apnea, Obstructive, White People, Medical and Health Sciences, Genetics & Heredity
Abstract

Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO2) and percentage time SaO2

Published
2019

231. Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry

Author

Irvin, Marguerite R, Sitlani, Colleen M, Noordam, Raymond, Avery, Christie L, Bis, Joshua C, Floyd, James S, Li, Jin, Limdi, Nita A, Srinivasasainagendra, Vinodh, Stewart, James, de Mutsert, Renée, Mook-Kanamori, Dennis O, Lipovich, Leonard, Kleinbrink, Erica L, Smith, Albert, Bartz, Traci M, Whitsel, Eric A, Uitterlinden, Andre G, Wiggins, Kerri L, Wilson, James G, Zhi, Degui, Stricker, Bruno H, Rotter, Jerome I, Arnett, Donna K, Psaty, Bruce M, and Lange, Leslie A

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Health Disparities, Human Genome, Genetics, Prevention, Minority Health, Black or African American, Aged, Antihypertensive Agents, Chromosomes, Human, Pair 5, Europe, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Peptidyl-Dipeptidase A, Polymorphism, Single Nucleotide, Potassium, Sodium Chloride Symporter Inhibitors, White People, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

We evaluated interactions of SNP-by-ACE-I/ARB and SNP-by-TD on serum potassium (K+) among users of antihypertensive treatments (anti-HTN). Our study included seven European-ancestry (EA) (N = 4835) and four African-ancestry (AA) cohorts (N = 2016). We performed race-stratified, fixed-effect, inverse-variance-weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates; race-combined meta-analysis; and trans-ethnic fine-mapping. Among EAs, we identified 11 significant SNPs (P

Published
2019

232. Identification of Novel Loci Associated With Hip Shape: A Meta‐Analysis of Genomewide Association Studies

Author

Baird, Denis A, Evans, Daniel S, Kamanu, Frederick K, Gregory, Jennifer S, Saunders, Fiona R, Giuraniuc, Claudiu V, Barr, Rebecca J, Aspden, Richard M, Jenkins, Deborah, Kiel, Douglas P, Orwoll, Eric S, Cummings, Steven R, Lane, Nancy E, Mullin, Benjamin H, Williams, Frances MK, Richards, J Brent, Wilson, Scott G, Spector, Tim D, Faber, Benjamin G, Lawlor, Deborah A, Grundberg, Elin, Ohlsson, Claes, Pettersson‐Kymmer, Ulrika, Capellini, Terence D, Richard, Daniel, Beck, Thomas J, Evans, David M, Paternoster, Lavinia, Karasik, David, and Tobias, Jonathan H

Subjects
Prevention, Genetics, Osteoporosis, Arthritis, Aging, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Musculoskeletal, Animals, Bone Density, Femur Head, Genetic Loci, Genome-Wide Association Study, Hip Fractures, Humans, Linkage Disequilibrium, Longitudinal Studies, Mice, Osteoporotic Fractures, Polymorphism, Single Nucleotide, HIP SHAPE, OSTEOARTHRITIS, HIP FRACTURE RISK, DXA, GWAS, Biological Sciences, Engineering, Medical and Health Sciences, Anatomy & Morphology
Abstract

We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p  0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Published
2019

233. Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data

Author

He, Karen Y, Li, Xiaoyin, Kelly, Tanika N, Liang, Jingjing, Cade, Brian E, Assimes, Themistocles L, Becker, Lewis C, Beitelshees, Amber L, Bress, Adam P, Chang, Yen-Pei Christy, Chen, Yii-Der Ida, de Vries, Paul S, Fox, Ervin R, Franceschini, Nora, Furniss, Anna, Gao, Yan, Guo, Xiuqing, Haessler, Jeffrey, Hwang, Shih-Jen, Irvin, Marguerite Ryan, Kalyani, Rita R, Liu, Ching-Ti, Liu, Chunyu, Martin, Lisa Warsinger, Montasser, May E, Muntner, Paul M, Mwasongwe, Stanford, Palmas, Walter, Reiner, Alex P, Shimbo, Daichi, Smith, Jennifer A, Snively, Beverly M, Yanek, Lisa R, Boerwinkle, Eric, Correa, Adolfo, Cupples, L Adrienne, He, Jiang, Kardia, Sharon LR, Kooperberg, Charles, Mathias, Rasika A, Mitchell, Braxton D, Psaty, Bruce M, Vasan, Ramachandran S, Rao, DC, Rich, Stephen S, Rotter, Jerome I, Wilson, James G, Chakravarti, Aravinda, Morrison, Alanna C, Levy, Daniel, Arnett, Donna K, Redline, Susan, and Zhu, Xiaofeng

Subjects
Biological Sciences, Genetics, Biotechnology, Heart Disease, Human Genome, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Alternative Splicing, Blood Pressure, Chromosomes, Human, Pair 16, Exome, Female, Follow-Up Studies, Genetic Linkage, Genetic Variation, Genome, Human, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Humans, Male, RNA Splicing Factors, Recombinases, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Blood Pressure Working Group, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p

Published
2019

234. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial.

Author

Matthay, Michael A, Calfee, Carolyn S, Zhuo, Hanjing, Thompson, B Taylor, Wilson, Jennifer G, Levitt, Joseph E, Rogers, Angela J, Gotts, Jeffrey E, Wiener-Kronish, Jeanine P, Bajwa, Ednan K, Donahoe, Michael P, McVerry, Bryan J, Ortiz, Luis A, Exline, Matthew, Christman, John W, Abbott, Jason, Delucchi, Kevin L, Caballero, Lizette, McMillan, Melanie, McKenna, David H, and Liu, Kathleen D

Subjects
Humans, Disease-Free Survival, Treatment Outcome, Mesenchymal Stem Cell Transplantation, Severity of Illness Index, Hospital Mortality, Multivariate Analysis, Proportional Hazards Models, Risk Assessment, Statistics, Nonparametric, Survival Analysis, Prospective Studies, Double-Blind Method, Adult, Aged, Middle Aged, Academic Medical Centers, United States, Female, Male, Patient Safety, Respiratory Distress Syndrome, Rare Diseases, Stem Cell Research, Acute Respiratory Distress Syndrome, Stem Cell Research - Nonembryonic - Human, Clinical Trials and Supportive Activities, Clinical Research, Lung, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Respiratory, Good Health and Well Being, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

BackgroundTreatment with bone-marrow-derived mesenchymal stromal cells (MSCs) has shown benefits in preclinical models of acute respiratory distress syndrome (ARDS). Safety has not been established for administration of MSCs in critically ill patients with ARDS. We did a phase 2a trial to assess safety after administration of MSCs to patients with moderate to severe ARDS.MethodsWe did a prospective, double-blind, multicentre, randomised trial to assess treatment with one intravenous dose of MSCs compared with placebo. We recruited ventilated patients with moderate to severe ARDS (ratio of partial pressure of oxygen to fractional inspired oxygen

Published
2019

235. Efficient Variant Set Mixed Model Association Tests for Continuous and Binary Traits in Large-Scale Whole-Genome Sequencing Studies

Author

Chen, Han, Huffman, Jennifer E, Brody, Jennifer A, Wang, Chaolong, Lee, Seunggeun, Li, Zilin, Gogarten, Stephanie M, Sofer, Tamar, Bielak, Lawrence F, Bis, Joshua C, Blangero, John, Bowler, Russell P, Cade, Brian E, Cho, Michael H, Correa, Adolfo, Curran, Joanne E, de Vries, Paul S, Glahn, David C, Guo, Xiuqing, Johnson, Andrew D, Kardia, Sharon, Kooperberg, Charles, Lewis, Joshua P, Liu, Xiaoming, Mathias, Rasika A, Mitchell, Braxton D, O’Connell, Jeffrey R, Peyser, Patricia A, Post, Wendy S, Reiner, Alex P, Rich, Stephen S, Rotter, Jerome I, Silverman, Edwin K, Smith, Jennifer A, Vasan, Ramachandran S, Wilson, James G, Yanek, Lisa R, Consortium, NHLBI Trans-Omics for Precision Medicine, Group, TOPMed Hematology and Hemostasis Working, Redline, Susan, Smith, Nicholas L, Boerwinkle, Eric, Borecki, Ingrid B, Cupples, L Adrienne, Laurie, Cathy C, Morrison, Alanna C, Rice, Kenneth M, and Lin, Xihong

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.5 Research design and methodologies (aetiology), Generic health relevance, Good Health and Well Being, Chromosomes, Human, Pair 4, Cloud Computing, Female, Fibrinogen, Genetic Association Studies, Genetics, Population, Humans, Male, Models, Genetic, National Heart, Lung, and Blood Institute (U.S.), Precision Medicine, Research Design, Time Factors, United States, Whole Genome Sequencing, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Hematology and Hemostasis Working Group, TOPMed, generalized linear mixed model, population structure, rare variants, relatedness, variant set association test, whole-genome sequencing, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

With advances in whole-genome sequencing (WGS) technology, more advanced statistical methods for testing genetic association with rare variants are being developed. Methods in which variants are grouped for analysis are also known as variant-set, gene-based, and aggregate unit tests. The burden test and sequence kernel association test (SKAT) are two widely used variant-set tests, which were originally developed for samples of unrelated individuals and later have been extended to family data with known pedigree structures. However, computationally efficient and powerful variant-set tests are needed to make analyses tractable in large-scale WGS studies with complex study samples. In this paper, we propose the variant-set mixed model association tests (SMMAT) for continuous and binary traits using the generalized linear mixed model framework. These tests can be applied to large-scale WGS studies involving samples with population structure and relatedness, such as in the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program. SMMATs share the same null model for different variant sets, and a virtue of this null model, which includes covariates only, is that it needs to be fit only once for all tests in each genome-wide analysis. Simulation studies show that all the proposed SMMATs correctly control type I error rates for both continuous and binary traits in the presence of population structure and relatedness. We also illustrate our tests in a real data example of analysis of plasma fibrinogen levels in the TOPMed program (n = 23,763), using the Analysis Commons, a cloud-based computing platform.

Published
2019

236. Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep

Author

Cade, Brian E, Chen, Han, Stilp, Adrienne M, Louie, Tin, Ancoli-Israel, Sonia, Arens, Raanan, Barfield, Richard, Below, Jennifer E, Cai, Jianwen, Conomos, Matthew P, Evans, Daniel S, Frazier-Wood, Alexis C, Gharib, Sina A, Gleason, Kevin J, Gottlieb, Daniel J, Hillman, David R, Johnson, W Craig, Lederer, David J, Lee, Jiwon, Loredo, Jose S, Mei, Hao, Mukherjee, Sutapa, Patel, Sanjay R, Post, Wendy S, Purcell, Shaun M, Ramos, Alberto R, Reid, Kathryn J, Rice, Ken, Shah, Neomi A, Sofer, Tamar, Taylor, Kent D, Thornton, Timothy A, Wang, Heming, Yaffe, Kristine, Zee, Phyllis C, Hanis, Craig L, Palmer, Lyle J, Rotter, Jerome I, Stone, Katie L, Tranah, Gregory J, Wilson, James G, Sunyaev, Shamil R, Laurie, Cathy C, Zhu, Xiaofeng, Saxena, Richa, Lin, Xihong, and Redline, Susan

Subjects
Genetics, Lung, Sleep Research, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Aged, Aged, 80 and over, Cell Adhesion Molecules, Neuronal, Computational Biology, Extracellular Matrix Proteins, Female, Gene Regulatory Networks, Genetic Variation, Genome-Wide Association Study, Hexokinase, Humans, Hypoxia, Interleukin-18 Receptor alpha Subunit, Male, Middle Aged, NLR Family, Pyrin Domain-Containing 3 Protein, Nerve Tissue Proteins, Oxygen, Oxyhemoglobins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reelin Protein, Serine Endopeptidases, Sleep, Sleep Apnea Syndromes, Young Adult, Developmental Biology
Abstract

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.

Published
2019

237. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author

Prins, Bram P, Mead, Timothy J, Brody, Jennifer A, Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A, van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T, Gabriel, George C, Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M, Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching-Ti, Lyytikäinen, Leo-Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V, Verweij, Niek, Warren, Helen R, Weiss, Stefan, Alonso, Alvaro, Arnar, David O, Bots, Michiel L, de Boer, Rudolf A, Dominiczak, Anna F, Eijgelsheim, Mark, Ellinor, Patrick T, Guo, Xiuqing, Felix, Stephan B, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Huang, Paul L, Jukema, JW, Kähönen, Mika, Kors, Jan A, Lambiase, Pier D, Launer, Lenore J, Li, Man, Linneberg, Allan, Nelson, Christopher P, Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M, Raitakari, Olli T, Rice, Kenneth M, Rotter, Jerome I, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Tim D, Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G, Xie, Zhijun, Asselbergs, Folkert W, Dörr, Marcus, van Duijn, Cornelia M, Gasparini, Paolo, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J, Lubitz, Steven A, Mook-Kanamori, Dennis O, Conti, Francesco J, Newton-Cheh, Christopher H, Rosand, Jonathan, Rudan, Igor, and Samani, Nilesh J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Human Genome, Heart Disease, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, ADAMTS Proteins, Animals, Black People, Connexin 43, Electrocardiography, Exome, Female, Gene Expression, Gene Expression Profiling, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Humans, Male, Mice, Middle Aged, Myocardium, Open Reading Frames, Polymorphism, Single Nucleotide, White People, Exome Sequencing, Exome chip, Conduction, ADAMTS6, Meta-analysis, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundGenome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.ResultsHere, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.ConclusionsOur approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.

Published
2018

238. Spatially and Temporally Distributed Data Foraging Decisions in Disciplinary Field Science

Author

Wilson, Cristina G., Qian, Feifei, Jerolmack, Douglas J., Roberts, Sonia, Ham, Jonathan, Koditschek, Daniel, and Shipley, Thomas F.

Abstract

How do scientists generate and weight candidate queries for hypothesis testing, and how does learning from observations or experimental data impact query selection? Field sciences offer a compelling context to ask these questions because query selection and adaptation involves consideration of the spatiotemporal arrangement of data, and therefore closely parallels classic search and foraging behavior. Here we conduct a novel simulated data foraging study--and a complementary real-world case study--to determine how spatiotemporal data collection decisions are made in field sciences, and how search is adapted in response to in-situ data. Expert geoscientists evaluated a hypothesis by collecting environmental data using a mobile robot. At any point, participants were able to stop the robot and change their search strategy or make a conclusion about the hypothesis. We identified spatiotemporal reasoning heuristics, to which scientists strongly anchored, displaying limited adaptation to new data. We analyzed two key decision factors: variable-space coverage, and fitting error to the hypothesis. We found that, despite varied search strategies, the majority of scientists made a conclusion as the fitting error converged. Scientists who made premature conclusions, due to insufficient variable-space coverage or before the fitting error stabilized, were more prone to incorrect conclusions. We found that novice undergraduates used the same heuristics as expert geoscientists in a simplified version of the scenario. We believe the findings from this study could be used to improve field science training in data foraging, and aid in the development of technologies to support data collection decisions.

Published
2021
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239. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Author

Mahajan, Anubha, Spracklen, Cassandra N., Zhang, Weihua, Ng, Maggie C. Y., Petty, Lauren E., Kitajima, Hidetoshi, Yu, Grace Z., Rüeger, Sina, Speidel, Leo, Kim, Young Jin, Horikoshi, Momoko, Mercader, Josep M., Taliun, Daniel, Moon, Sanghoon, Kwak, Soo-Heon, Robertson, Neil R., Rayner, Nigel W., Loh, Marie, Kim, Bong-Jo, Chiou, Joshua, Miguel-Escalada, Irene, della Briotta Parolo, Pietro, Lin, Kuang, Bragg, Fiona, Preuss, Michael H., Takeuchi, Fumihiko, Nano, Jana, Guo, Xiuqing, Lamri, Amel, Nakatochi, Masahiro, Scott, Robert A., Lee, Jung-Jin, Huerta-Chagoya, Alicia, Graff, Mariaelisa, Chai, Jin-Fang, Parra, Esteban J., Yao, Jie, Bielak, Lawrence F., Tabara, Yasuharu, Hai, Yang, Steinthorsdottir, Valgerdur, Cook, James P., Kals, Mart, Grarup, Niels, Schmidt, Ellen M., Pan, Ian, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloe, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Ahmad, Meraj, Noordam, Raymond, Lim, Victor J. Y., Tam, Claudia H. T., Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M., Lecoeur, Cécile, Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R., Chen, Guanjie, Jensen, Richard A., Tajuddin, Salman, Kabagambe, Edmond K., An, Ping, Xiang, Anny H., Choi, Hyeok Sun, Cade, Brian E., Tan, Jingyi, Flanagan, Jack, Abaitua, Fernando, Adair, Linda S., Adeyemo, Adebowale, Aguilar-Salinas, Carlos A., Akiyama, Masato, Anand, Sonia S., Bertoni, Alain, Bian, Zheng, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A., Brummett, Chad M., Buchanan, Thomas A., Canouil, Mickaël, Chan, Juliana C. N., Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Cushman, Mary, Das, Swapan K., de Silva, H. Janaka, Dedoussis, George, Dimitrov, Latchezar, Doumatey, Ayo P., Du, Shufa, Duan, Qing, Eckardt, Kai-Uwe, Emery, Leslie S., Evans, Daniel S., Evans, Michele K., Fischer, Krista, Floyd, James S., Ford, Ian, Fornage, Myriam, Franco, Oscar H., Frayling, Timothy M., Freedman, Barry I., Fuchsberger, Christian, Genter, Pauline, Gerstein, Hertzel C., Giedraitis, Vilmantas, González-Villalpando, Clicerio, González-Villalpando, Maria Elena, Goodarzi, Mark O., Gordon-Larsen, Penny, Gorkin, David, Gross, Myron, Guo, Yu, Hackinger, Sophie, Han, Sohee, Hattersley, Andrew T., Herder, Christian, Howard, Annie-Green, Hsueh, Willa, Huang, Mengna, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Ikram, Mohammad Arfan, Ingelsson, Martin, Islam, Md Tariqul, Isono, Masato, Jang, Hye-Mi, Jasmine, Farzana, Jiang, Guozhi, Jonas, Jost B., Jørgensen, Marit E., Jørgensen, Torben, Kamatani, Yoichiro, Kandeel, Fouad R., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kaur, Varinderpal, Kawaguchi, Takahisa, Keaton, Jacob M., Kho, Abel N., Khor, Chiea-Chuen, Kibriya, Muhammad G., Kim, Duk-Hwan, Kohara, Katsuhiko, Kriebel, Jennifer, Kronenberg, Florian, Kuusisto, Johanna, Läll, Kristi, Lange, Leslie A., Lee, Myung-Shik, Lee, Nanette R., Leong, Aaron, Li, Liming, Li, Yun, Li-Gao, Ruifang, Ligthart, Symen, Lindgren, Cecilia M., Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Locke, Adam E., Louie, Tin, Luan, Jian’an, Luk, Andrea O., Luo, Xi, Lv, Jun, Lyssenko, Valeriya, Mamakou, Vasiliki, Mani, K. Radha, Meitinger, Thomas, Metspalu, Andres, Morris, Andrew D., Nadkarni, Girish N., Nadler, Jerry L., Nalls, Michael A., Nayak, Uma, Nongmaithem, Suraj S., Ntalla, Ioanna, Okada, Yukinori, Orozco, Lorena, Patel, Sanjay R., Pereira, Mark A., Peters, Annette, Pirie, Fraser J., Porneala, Bianca, Prasad, Gauri, Preissl, Sebastian, Rasmussen-Torvik, Laura J., Reiner, Alexander P., Roden, Michael, Rohde, Rebecca, Roll, Kathryn, Sabanayagam, Charumathi, Sander, Maike, Sandow, Kevin, Sattar, Naveed, Schönherr, Sebastian, Schurmann, Claudia, Shahriar, Mohammad, Shi, Jinxiu, Shin, Dong Mun, Shriner, Daniel, Smith, Jennifer A., So, Wing Yee, Stančáková, Alena, Stilp, Adrienne M., Strauch, Konstantin, Suzuki, Ken, Takahashi, Atsushi, Taylor, Kent D., Thorand, Barbara, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tomlinson, Brian, Torres, Jason M., Tsai, Fuu-Jen, Tuomilehto, Jaakko, Tusie-Luna, Teresa, Udler, Miriam S., Valladares-Salgado, Adan, van Dam, Rob M., van Klinken, Jan B., Varma, Rohit, Vujkovic, Marijana, Wacher-Rodarte, Niels, Wheeler, Eleanor, Whitsel, Eric A., Wickremasinghe, Ananda R., van Dijk, Ko Willems, Witte, Daniel R., Yajnik, Chittaranjan S., Yamamoto, Ken, Yamauchi, Toshimasa, Yengo, Loïc, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Yusuf, Salim, Zhang, Liang, Zheng, Wei, Raffel, Leslie J., Igase, Michiya, Ipp, Eli, Redline, Susan, Cho, Yoon Shin, Lind, Lars, Province, Michael A., Hanis, Craig L., Peyser, Patricia A., Ingelsson, Erik, Zonderman, Alan B., Psaty, Bruce M., Wang, Ya-Xing, Rotimi, Charles N., Becker, Diane M., Matsuda, Fumihiko, Liu, Yongmei, Zeggini, Eleftheria, Yokota, Mitsuhiro, Rich, Stephen S., Kooperberg, Charles, Pankow, James S., Engert, James C., Chen, Yii-Der Ida, Froguel, Philippe, Wilson, James G., Sheu, Wayne H. H., Kardia, Sharon L. R., Wu, Jer-Yuarn, Hayes, M. Geoffrey, Ma, Ronald C. W., Wong, Tien-Yin, Groop, Leif, Mook-Kanamori, Dennis O., Chandak, Giriraj R., Collins, Francis S., Bharadwaj, Dwaipayan, Paré, Guillaume, Sale, Michèle M., Ahsan, Habibul, Motala, Ayesha A., Shu, Xiao-Ou, Park, Kyong-Soo, Jukema, J. Wouter, Cruz, Miguel, McKean-Cowdin, Roberta, Grallert, Harald, Cheng, Ching-Yu, Bottinger, Erwin P., Dehghan, Abbas, Tai, E-Shyong, Dupuis, Josée, Kato, Norihiro, Laakso, Markku, Köttgen, Anna, Koh, Woon-Puay, Palmer, Colin N. A., Liu, Simin, Abecasis, Goncalo, Kooner, Jaspal S., Loos, Ruth J. F., North, Kari E., Haiman, Christopher A., Florez, Jose C., Saleheen, Danish, Hansen, Torben, Pedersen, Oluf, Mägi, Reedik, Langenberg, Claudia, Wareham, Nicholas J., Maeda, Shiro, Kadowaki, Takashi, Lee, Juyoung, Millwood, Iona Y., Walters, Robin G., Stefansson, Kari, Myers, Simon R., Ferrer, Jorge, Gaulton, Kyle J., Meigs, James B., Mohlke, Karen L., Gloyn, Anna L., Bowden, Donald W., Below, Jennifer E., Chambers, John C., Sim, Xueling, Boehnke, Michael, Rotter, Jerome I., McCarthy, Mark I., and Morris, Andrew P.

Published
2022
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242. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author

Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki V., Hutri-Kähönen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O’Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome I., Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.

Published
2022
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245. Author Correction: Proteolytic processing induces a conformational switch required for antibacterial toxin delivery

Author

Bartelli, Nicholas L., Passanisi, Victor J., Michalska, Karolina, Song, Kiho, Nhan, Dinh Q., Zhou, Hongjun, Cuthbert, Bonnie J., Stols, Lucy M., Eschenfeldt, William H., Wilson, Nicholas G., Basra, Jesse S., Cortes, Ricardo, Noorsher, Zainab, Gabraiel, Youssef, Poonen-Honig, Isaac, Seacord, Elizabeth C., Goulding, Celia W., Low, David A., Joachimiak, Andrzej, Dahlquist, Frederick W., and Hayes, Christopher S.

Published
2022
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246. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Author

Kanoni, Stavroula, Graham, Sarah E., Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L., Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J. M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Yousri, Noha A., Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, EWarwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Vazquez-Moreno, Miguel, Feitosa, Mary F., Wojczynski, Mary K., Wang, Zhe, Preuss, Michael H., Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Tsao, Noah L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Frank, Mirjam, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Bayyana, Swati, Stringham, Heather M., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Nardone, Giuseppe Giovanni, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R. B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Liang, Jingjing, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, Hollander, Anneke Iden, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Costanzo, Maria C., Jang, Dongkeun, Burtt, Noël P., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M.‘t, Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., Willemsen, Allegonda H. M., Cupples, LAdrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, YEugene, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter W. F., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Mohlke, Karen L., Sun, Yan V., Morris, Andrew P., Boehnke, Michael, Brown, Christopher D., Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J., Assimes, Themistocles L., and Peloso, Gina M.

Published
2022
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249. $\textit{Herschel}$/SPIRE Observations of Water Production Rates and Ortho-to-Para Ratios in Comets

Author

Wilson, Thomas G., Rawlings, Jonathan M. C., and Swinyard, Bruce M.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

This paper presents $\textit{Herschel}$/SPIRE spectroscopic observations of several fundamental rotational ortho- and para-water transitions seen in three Jupiter-family comets and one Oort-cloud comet. Radiative transfer models that include excitation by collisions with neutrals and electrons, and by solar infrared radiation were used to produce synthetic emission line profiles originating in the cometary coma. Ortho-to-para ratios (OPRs) were determined and used to derived water production rates for all comets. Comparisons are made with the water production rates derived using an OPR of 3. The OPR of three of the comets in this study are much lower than the statistical equilibrium value of 3, however they agree with observations of comets 1P/Halley and C/2001 A2 (LINEAR), and the protoplanetary disc TW Hydrae. These results provide evidence suggesting that OPR variation is caused by post-sublimation gas-phase nuclear-spin conversion processes. The water production rates of all comets agree with previous work and, in general, decrease with increasing nucleocentric offset. This could be due to a temperature profile, additional water source, or OPR variation in the comae, or model inaccuracies., Comment: 9 pages, 2 figures, 3 tables; accepted for publication in MNRAS

Published
2016
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250. Evidence of Vulnerability to Decision Bias in Expert Field Scientists

Author

Wilson, Cristina G., Shipley, Thomas F., and Davatzes, Alexandra K.

Abstract

Previous research demonstrates that domain experts, like ordinary participant populations, are vulnerable to decision bias. Here, we examine susceptibility to bias amongst expert field scientists. Field scientists operate in less predictable environments than other experts, and feedback on the consequences of their decisions is often unclear or delayed. Thus, field scientists are a population where the findings of scientific research may be particularly vulnerable to bias. In this study, susceptibility to optimism, hindsight, and framing bias was evaluated in a group of expert field geologists using descriptive decision scenarios. Experts showed susceptibility to all three biases, and susceptibility was not influenced by years of science practice. We found no evidence that participants' vulnerability to one bias was related to their vulnerability to another bias. Our findings are broadly consistent with previous research on expertise and decision bias, demonstrating that no expert, regardless their domain experience, is immune to bias.

Published
2020
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