1,043 results on '"Raby, Benjamin"'
Search Results
2. Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes
- Author
-
Keener, Rebecca, Chhetri, Surya B, Connelly, Carla J, Taub, Margaret A, Conomos, Matthew P, Weinstock, Joshua, Ni, Bohan, Strober, Benjamin, Aslibekyan, Stella, Auer, Paul L, Barwick, Lucas, Becker, Lewis C, Blangero, John, Bleecker, Eugene R, Brody, Jennifer A, Cade, Brian E, Celedon, Juan C, Chang, Yi-Cheng, Cupples, L Adrienne, Custer, Brian, Freedman, Barry I, Gladwin, Mark T, Heckbert, Susan R, Hou, Lifang, Irvin, Marguerite R, Isasi, Carmen R, Johnsen, Jill M, Kenny, Eimear E, Kooperberg, Charles, Minster, Ryan L, Naseri, Take, Viali, Satupa’itea, Nekhai, Sergei, Pankratz, Nathan, Peyser, Patricia A, Taylor, Kent D, Telen, Marilyn J, Wu, Baojun, Yanek, Lisa R, Yang, Ivana V, Albert, Christine, Arnett, Donna K, Ashley-Koch, Allison E, Barnes, Kathleen C, Bis, Joshua C, Blackwell, Thomas W, Boerwinkle, Eric, Burchard, Esteban G, Carson, April P, Chen, Zhanghua, Chen, Yii-Der Ida, Darbar, Dawood, de Andrade, Mariza, Ellinor, Patrick T, Fornage, Myriam, Gelb, Bruce D, Gilliland, Frank D, He, Jiang, Islam, Talat, Kaab, Stefan, Kardia, Sharon LR, Kelly, Shannon, Konkle, Barbara A, Kumar, Rajesh, Loos, Ruth JF, Martinez, Fernando D, McGarvey, Stephen T, Meyers, Deborah A, Mitchell, Braxton D, Montgomery, Courtney G, North, Kari E, Palmer, Nicholette D, Peralta, Juan M, Raby, Benjamin A, Redline, Susan, Rich, Stephen S, Roden, Dan, Rotter, Jerome I, Ruczinski, Ingo, Schwartz, David, Sciurba, Frank, Shoemaker, M Benjamin, Silverman, Edwin K, Sinner, Moritz F, Smith, Nicholas L, Smith, Albert V, Tiwari, Hemant K, Vasan, Ramachandran S, Weiss, Scott T, Williams, L Keoki, Zhang, Yingze, Ziv, Elad, Raffield, Laura M, Reiner, Alexander P, Arvanitis, Marios, Greider, Carol W, Mathias, Rasika A, and Battle, Alexis
- Subjects
Biological Sciences ,Genetics ,Human Genome ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Generic health relevance ,Humans ,Genome-Wide Association Study ,Telomere ,K562 Cells ,Telomere Homeostasis ,Polymorphism ,Single Nucleotide ,Gene Expression Regulation ,CRISPR-Cas Systems ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium ,TOPMed Hematology and Hemostasis Working Group ,TOPMed Structural Variation Working Group - Abstract
Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.
- Published
- 2024
3. Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling
- Author
-
Kim, Hyunbum, Liu, Yu, Kim, Jiwon, Kim, Yunhye, Klouda, Timothy, Fisch, Sudeshna, Baek, Seung Han, Liu, Tiffany, Dahlberg, Suzanne, Hu, Cheng-Jun, Tian, Wen, Jiang, Xinguo, Kosmas, Kosmas, Christou, Helen A, Korman, Benjamin D, Vargas, Sara O, Wu, Joseph C, Stenmark, Kurt R, Perez, Vinicio de Jesus, Nicolls, Mark R, Raby, Benjamin A, and Yuan, Ke
- Published
- 2024
- Full Text
- View/download PDF
4. Abstract 4116949: Specialized Pericyte Subtypes in the Pulmonary Capillary
- Author
-
Klouda, Tim, Kim, Yunhye, Baek, Han-Seong, Bhaumik, Mantu, Liu, Yu, Liu, Tiffany, Que, Jianwen, Wu, Joseph, Raby, Benjamin, Dejesus, Vinicio, and Yuan, Ke
- Published
- 2024
- Full Text
- View/download PDF
5. Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling.
- Author
-
Holtz, Alexander, VanCoillie, Rachel, Vansickle, Elizabeth, Carere, Deanna, Withrow, Kara, Torti, Erin, Juusola, Jane, Millan, Francisca, Person, Richard, Guillen Sacoto, Maria, Si, Yue, Wentzensen, Ingrid, Pugh, Jada, Vasileiou, Georgia, Rieger, Melissa, Reis, André, Aldinger, Kimberly, Dobyns, William, Brunet, Theresa, Hoefele, Julia, Wagner, Matias, Haber, Benjamin, Kotzaeridou, Urania, Keren, Boris, Heron, Delphine, Mignot, Cyril, Heide, Solveig, Courtin, Thomas, Buratti, Julien, Murugasen, Serini, Donald, Kirsten, OHeir, Emily, Moody, Shade, Kim, Katherine, Burton, Barbara, Yoon, Grace, Campo, Miguel, Masser-Frye, Diane, Kozenko, Mariya, Parkinson, Christina, Sell, Susan, Gordon, Patricia, Prokop, Jeremy, Karaa, Amel, Bupp, Caleb, Raby, Benjamin, Sherr, Elliott, and Argilli, Emanuela
- Subjects
Hedgehog signaling ,MYH10 ,Neurodevelopmental disorder ,Nonmuscle myosin ,Primary cilia ,Actins ,Cilia ,Hedgehog Proteins ,Humans ,Myosin Heavy Chains ,Neurodevelopmental Disorders ,Nonmuscle Myosin Type IIB - Abstract
PURPOSE: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10. METHODS: An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis. RESULTS: We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a broad spectrum of neurodevelopmental disorders and variable congenital anomalies that affect most organ systems and were recapitulated in animal models of altered MYH10 activity. Variants were typically de novo missense changes with clustering observed in the motor domain. MYH10 knockout cells showed defects in primary ciliogenesis and reduced ciliary length with impaired Hedgehog signaling. MYH10 variant overexpression produced a dominant-negative effect on ciliary length. CONCLUSION: These data presented a novel genetic cause of isolated and syndromic neurodevelopmental disorders related to heterozygous variants in the MYH10 gene with implications for disrupted primary cilia length control and altered Hedgehog signaling in disease pathogenesis.
- Published
- 2022
6. Biomarker-Based Risk Stratification Tool in Pediatric Acute Respiratory Distress Syndrome: Single-Center, Longitudinal Validation in a 2014–2019 Cohort
- Author
-
Whitney, Jane E., Johnson, Grace M., Varisco, Brian M., Raby, Benjamin A., and Yehya, Nadir
- Published
- 2024
- Full Text
- View/download PDF
7. Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed
- Author
-
Taub, Margaret A, Conomos, Matthew P, Keener, Rebecca, Iyer, Kruthika R, Weinstock, Joshua S, Yanek, Lisa R, Lane, John, Miller-Fleming, Tyne W, Brody, Jennifer A, Raffield, Laura M, McHugh, Caitlin P, Jain, Deepti, Gogarten, Stephanie M, Laurie, Cecelia A, Keramati, Ali, Arvanitis, Marios, Smith, Albert V, Heavner, Benjamin, Barwick, Lucas, Becker, Lewis C, Bis, Joshua C, Blangero, John, Bleecker, Eugene R, Burchard, Esteban G, Celedón, Juan C, Chang, Yen Pei C, Custer, Brian, Darbar, Dawood, de las Fuentes, Lisa, DeMeo, Dawn L, Freedman, Barry I, Garrett, Melanie E, Gladwin, Mark T, Heckbert, Susan R, Hidalgo, Bertha A, Irvin, Marguerite R, Islam, Talat, Johnson, W Craig, Kaab, Stefan, Launer, Lenore, Lee, Jiwon, Liu, Simin, Moscati, Arden, North, Kari E, Peyser, Patricia A, Rafaels, Nicholas, Seidman, Christine, Weeks, Daniel E, Wen, Fayun, Wheeler, Marsha M, Williams, L Keoki, Yang, Ivana V, Zhao, Wei, Aslibekyan, Stella, Auer, Paul L, Bowden, Donald W, Cade, Brian E, Chen, Zhanghua, Cho, Michael H, Cupples, L Adrienne, Curran, Joanne E, Daya, Michelle, Deka, Ranjan, Eng, Celeste, Fingerlin, Tasha E, Guo, Xiuqing, Hou, Lifang, Hwang, Shih-Jen, Johnsen, Jill M, Kenny, Eimear E, Levin, Albert M, Liu, Chunyu, Minster, Ryan L, Naseri, Take, Nouraie, Mehdi, Reupena, Muagututi A Sefuiva, Sabino, Ester C, Smith, Jennifer A, Smith, Nicholas L, Lasky-Su, Jessica, Taylor, James G, Telen, Marilyn J, Tiwari, Hemant K, Tracy, Russell P, White, Marquitta J, Zhang, Yingze, Wiggins, Kerri L, Weiss, Scott T, Vasan, Ramachandran S, Taylor, Kent D, Sinner, Moritz F, Silverman, Edwin K, Shoemaker, M Benjamin, Sheu, Wayne H-H, Sciurba, Frank, Schwartz, David A, Rotter, Jerome I, Roden, Daniel, Redline, Susan, and Raby, Benjamin A
- Subjects
Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Human Genome ,Biotechnology ,Aetiology ,2.1 Biological and endogenous factors ,Generic health relevance ,Good Health and Well Being ,NHLBI CARE Network ,NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium ,TOPMed Hematology and Hemostasis Working Group ,TOPMed Structural Variation Working Group - Abstract
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value
- Published
- 2022
8. Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial
- Author
-
Ringshausen, Felix C, Shapiro, Adam J, Nielsen, Kim G, Mazurek, Henryk, Pifferi, Massimo, Donn, Karl H, van der Eerden, Menno M, Loebinger, Michael R, Zariwala, Maimoona A, Leigh, Margaret W, Knowles, Michael R, Ferkol, Jr, Thomas W, Brown, Trey, Carroll, Mary, Church, Nina, Couluris, Marisa, Davis, Stephanie D, Dell, Sharon D, Di Cicco, Maria E, Di Mango, Angela, Escobar, Hugo, Griffiths, Anne, Haver, Kenan, Hornick, Douglas, Johnson, Christopher, Milla, Carlos E, O'Donnell, Anne, Pink, Isabell, Pogorzelski, Andrzej, Prickett, Michelle, Raby, Benjamin A, Rosenfeld, Margaret, Saba, Thomas G, Sandvik, Rikke Mulvad, Sagel, Scott D, Salathe, Matthias, Simmons, Ashley E, Solomon, George M, Sommerburg, Olaf, Soussi, Najwa, Strausbaugh, Steven D, Sullivan, Kelli M, Werner, Claudius, and Ferkol, Thomas W
- Published
- 2024
- Full Text
- View/download PDF
9. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
- Author
-
Budu-Aggrey, Ashley, Kilanowski, Anna, Sobczyk, Maria K., Shringarpure, Suyash S., Mitchell, Ruth, Reis, Kadri, Reigo, Anu, Mägi, Reedik, Nelis, Mari, Tanaka, Nao, Brumpton, Ben M., Thomas, Laurent F., Sole-Navais, Pol, Flatley, Christopher, Espuela-Ortiz, Antonio, Herrera-Luis, Esther, Lominchar, Jesus V. T., Bork-Jensen, Jette, Marenholz, Ingo, Arnau-Soler, Aleix, Jeong, Ayoung, Fawcett, Katherine A., Baurecht, Hansjorg, Rodriguez, Elke, Alves, Alexessander Couto, Kumar, Ashish, Sleiman, Patrick M., Chang, Xiao, Medina-Gomez, Carolina, Hu, Chen, Xu, Cheng-jian, Qi, Cancan, El-Heis, Sarah, Titcombe, Philip, Antoun, Elie, Fadista, João, Wang, Carol A., Thiering, Elisabeth, Wu, Baojun, Kress, Sara, Kothalawala, Dilini M., Kadalayil, Latha, Duan, Jiasong, Zhang, Hongmei, Hadebe, Sabelo, Hoffmann, Thomas, Jorgenson, Eric, Choquet, Hélène, Risch, Neil, Njølstad, Pål, Andreassen, Ole A., Johansson, Stefan, Almqvist, Catarina, Gong, Tong, Ullemar, Vilhelmina, Karlsson, Robert, Magnusson, Patrik K. E., Szwajda, Agnieszka, Burchard, Esteban G., Thyssen, Jacob P., Hansen, Torben, Kårhus, Line L., Dantoft, Thomas M., Jeanrenaud, Alexander C.S.N., Ghauri, Ahla, Arnold, Andreas, Homuth, Georg, Lau, Susanne, Nöthen, Markus M., Hübner, Norbert, Imboden, Medea, Visconti, Alessia, Falchi, Mario, Bataille, Veronique, Hysi, Pirro, Ballardini, Natalia, Boomsma, Dorret I., Hottenga, Jouke J., Müller-Nurasyid, Martina, Ahluwalia, Tarunveer S., Stokholm, Jakob, Chawes, Bo, Schoos, Ann-Marie M., Esplugues, Ana, Bustamante, Mariona, Raby, Benjamin, Arshad, Syed, German, Chris, Esko, Tõnu, Milani, Lili A., Metspalu, Andres, Terao, Chikashi, Abuabara, Katrina, Løset, Mari, Hveem, Kristian, Jacobsson, Bo, Pino-Yanes, Maria, Strachan, David P., Grarup, Niels, Linneberg, Allan, Lee, Young-Ae, Probst-Hensch, Nicole, Weidinger, Stephan, Jarvelin, Marjo-Riitta, Melén, Erik, Hakonarson, Hakon, Irvine, Alan D., Jarvis, Deborah, Nijsten, Tamar, Duijts, Liesbeth, Vonk, Judith M., Koppelmann, Gerard H., Godfrey, Keith M., Barton, Sheila J., Feenstra, Bjarke, Pennell, Craig E., Sly, Peter D., Holt, Patrick G., Williams, L. Keoki, Bisgaard, Hans, Bønnelykke, Klaus, Curtin, John, Simpson, Angela, Murray, Clare, Schikowski, Tamara, Bunyavanich, Supinda, Weiss, Scott T., Holloway, John W., Min, Josine L., Brown, Sara J., Standl, Marie, and Paternoster, Lavinia
- Published
- 2023
- Full Text
- View/download PDF
10. An intronic variant in TBX4 in a single family with variable and severe pulmonary manifestations
- Author
-
Flanagan, Frances O., Holtz, Alexander M., Vargas, Sara O., Genetti, Casie A., Schmitz-Abe, Klaus, Casey, Alicia, Kennedy, John C., Raby, Benjamin A., Mullen, Mary P., Fishman, Martha P., and Agrawal, Pankaj B.
- Published
- 2023
- Full Text
- View/download PDF
11. 735: IMPLEMENTATION OF A PEDIATRIC PULMONARY POST-ICU CLINIC: LESSONS LEARNED AND FUTURE DIRECTIONS
- Author
-
Johnson, Grace, Raby, Benjamin, Agus, Michael, Kelly, Daniel, Perkins, Ryan, Midyat, Levent, Steiding, Jacqueline, Rabinowitz, Elliot, and Whitney, Jane
- Published
- 2024
- Full Text
- View/download PDF
12. Expression of SMARCD1 interacts with age in association with asthma control on inhaled corticosteroid therapy
- Author
-
McGeachie, Michael J, Sordillo, Joanne E, Dahlin, Amber, Wang, Alberta L, Lutz, Sharon M, Tantisira, Kelan G, Panganiban, Ronald, Lu, Quan, Sajuthi, Satria, Urbanek, Cydney, Kelly, Rachel, Saef, Benjamin, Eng, Celeste, Oh, Sam S, Kho, Alvin T, Croteau-Chonka, Damien C, Weiss, Scott T, Raby, Benjamin A, Mak, Angel CY, Rodriguez-Santana, Jose R, Burchard, Esteban G, Seibold, Max A, and Wu, Ann Chen
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Asthma ,Biotechnology ,Genetics ,Clinical Research ,Human Genome ,Lung ,Aetiology ,2.1 Biological and endogenous factors ,Respiratory ,Administration ,Inhalation ,Adolescent ,Adrenal Cortex Hormones ,Adult ,Age Factors ,Child ,Chromosomal Proteins ,Non-Histone ,Cohort Studies ,Female ,Gene Expression ,Hispanic or Latino ,Humans ,Male ,Middle Aged ,Treatment Outcome ,Young Adult ,Cardiorespiratory Medicine and Haematology ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundGlobal gene expression levels are known to be highly dependent upon gross demographic features including age, yet identification of age-related genomic indicators has yet to be comprehensively undertaken in a disease and treatment-specific context.MethodsWe used gene expression data from CD4+ lymphocytes in the Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE), an open-access collection of subjects participating in genetic studies of asthma with available gene expression data. Replication population participants were Puerto Rico islanders recruited as part of the ongoing Genes environments & Admixture in Latino Americans (GALA II), who provided nasal brushings for transcript sequencing. The main outcome measure was chronic asthma control as derived by questionnaires. Genomic associations were performed using regression of chronic asthma control score on gene expression with age in years as a covariate, including a multiplicative interaction term for gene expression times age.ResultsThe SMARCD1 gene (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1) interacted with age to influence chronic asthma control on inhaled corticosteroids, with a doubling of expression leading to an increase of 1.3 units of chronic asthma control per year (95% CI [0.86, 1.74], p = 6 × 10- 9), suggesting worsening asthma control with increasing age. This result replicated in GALA II (p = 3.8 × 10- 8). Cellular assays confirmed the role of SMARCD1 in glucocorticoid response in airway epithelial cells.ConclusionFocusing on age-dependent factors may help identify novel indicators of asthma medication response. Age appears to modulate the effect of SMARCD1 on asthma control with inhaled corticosteroids.
- Published
- 2020
13. Abstract 17142: Deficiency of Smooth Muscle ADAR1 Exacerbates Vascular Remodeling and Pulmonary Hypertension
- Author
-
Kim, Yunhye, Maroli, Giovanni, Woodcock, Chen-Shan J, Klouda, Tim, Hao, Yuan, Liu, Tiffany, Schumacher, Valerie A, Li, Jin B, Raby, Benjamin, Chan, Stephen, Pullamsetti, Soni, and Yuan, Ke
- Published
- 2023
- Full Text
- View/download PDF
14. Abstract 12185: Hypoxia Exacerbates Flow-Induced Vascular Remodeling via CXCL12/CXCR4 Pathway
- Author
-
Klouda, Tim, Tsiki, Savas, Liu, Tiffany, Kim, Yunhye, Visner, Gary A, Puder, Mark, Raby, Benjamin, and Yuan, Ke
- Published
- 2023
- Full Text
- View/download PDF
15. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma
- Author
-
Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L, Ahluwalia, Tarunveer S, Cho, Michael H, Qiao, Dandi, Kelly, Rachel S, Chu, Su H, Virkud, Yamini V, Huang, Mengna, Barnes, Kathleen C, Burchard, Esteban G, Eng, Celeste, Hu, Donglei, Celedón, Juan C, Daya, Michelle, Levin, Albert M, Gui, Hongsheng, Williams, L Keoki, Forno, Erick, Mak, Angel CY, Avila, Lydiana, Soto-Quiros, Manuel E, Cloutier, Michelle M, Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A, Lange, Christoph, Weiss, Scott T, Lasky-Su, Jessica A, National Heart, Lung, Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette Palmer, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, and Das, Sayantan
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Clinical Research ,Asthma ,Genetics ,Pediatric ,Biotechnology ,Human Genome ,Lung ,2.1 Biological and endogenous factors ,Respiratory ,Adolescent ,Adult ,Cell Adhesion Molecules ,Child ,Child ,Preschool ,Costa Rica ,Female ,Forced Expiratory Volume ,Humans ,Interferon Regulatory Factors ,Male ,Middle Aged ,Respiratory Physiological Phenomena ,Vital Capacity ,Whole Genome Sequencing ,Young Adult ,airway hyperresponsiveness ,asthma ,lung function ,whole genome sequencing ,National Heart ,Lung ,and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundAsthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.MethodsWGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes.ResultsA genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR.ConclusionsThese findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.
- Published
- 2019
16. An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos
- Author
-
Gignoux, Christopher R, Torgerson, Dara G, Pino-Yanes, Maria, Uricchio, Lawrence H, Galanter, Joshua, Roth, Lindsey A, Eng, Celeste, Hu, Donglei, Nguyen, Elizabeth A, Huntsman, Scott, Mathias, Rasika A, Kumar, Rajesh, Rodriguez-Santana, Jose, Thakur, Neeta, Oh, Sam S, McGarry, Meghan, Moreno-Estrada, Andres, Sandoval, Karla, Winkler, Cheryl A, Seibold, Max A, Padhukasahasram, Badri, Conti, David V, Farber, Harold J, Avila, Pedro, Brigino-Buenaventura, Emerita, Lenoir, Michael, Meade, Kelley, Serebrisky, Denise, Borrell, Luisa N, Rodriguez-Cintron, William, Thyne, Shannon, Joubert, Bonnie R, Romieu, Isabelle, Levin, Albert M, Sienra-Monge, Juan-Jose, Del Rio-Navarro, Blanca Estela, Gan, Weiniu, Raby, Benjamin A, Weiss, Scott T, Bleecker, Eugene, Meyers, Deborah A, Martinez, Fernando J, Gauderman, W James, Gilliland, Frank, London, Stephanie J, Bustamante, Carlos D, Nicolae, Dan L, Ober, Carole, Sen, Saunak, Barnes, Kathleen, Williams, L Keoki, Hernandez, Ryan D, and Burchard, Esteban G
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Human Genome ,Clinical Research ,Lung ,Asthma ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Respiratory ,Chromosome Mapping ,Chromosomes ,Human ,Pair 18 ,Genetic Predisposition to Disease ,Hispanic or Latino ,Humans ,Polymorphism ,Single Nucleotide ,Smad2 Protein ,asthma exacerbations ,admixture mapping ,meta-analysis ,Latinos ,SMAD2 ,gene expression ,targeted sequencing ,rare variation ,Allergy - Abstract
BackgroundAsthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.ObjectiveWe sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.MethodsWe leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.ResultsWe identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10-6), where Native American ancestry was associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07-1.34; P = .002) and European ancestry was associated with protection (OR, 0.86; 95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent childhood asthma study in Latinos (P = 5.3 × 10-3, combined P = 2.6 × 10-7). Fine mapping of 18q21 in 1978 Latinos identified a significant association with multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a single rare variant in the same window was the top association in Puerto Ricans. Low versus high SMAD2 blood expression was correlated with case status (13.4% lower expression; OR, 3.93; 95% CI, 2.12-7.28; P
- Published
- 2019
17. Interferon-alpha or -beta facilitates SARS-CoV-2 pulmonary vascular infection by inducing ACE2
- Author
-
Klouda, Timothy, Hao, Yuan, Kim, Hyunbum, Kim, Jiwon, Olejnik, Judith, Hume, Adam J., Ayyappan, Sowntharya, Hong, Xuechong, Melero-Martin, Juan, Fang, Yinshan, Wang, Qiong, Zhou, Xiaobo, Mühlberger, Elke, Jia, Hongpeng, Padera, Jr., Robert F., Raby, Benjamin A., and Yuan, Ke
- Published
- 2022
- Full Text
- View/download PDF
18. Inflammasome activation in neutrophils of patients with severe COVID-19
- Author
-
Aymonnier, Karen, Ng, Julie, Fredenburgh, Laura E., Zambrano-Vera, Katherin, Münzer, Patrick, Gutch, Sarah, Fukui, Shoichi, Desjardins, Michael, Subramaniam, Meera, Baron, Rebecca M, Raby, Benjamin A., Perrella, Mark A., Lederer, James A., and Wagner, Denisa D.
- Published
- 2022
- Full Text
- View/download PDF
19. Progenitor potential of lung epithelial organoid cells in a transplantation model
- Author
-
Louie, Sharon M., Moye, Aaron L., Wong, Irene G., Lu, Emery, Shehaj, Andrea, Garcia-de-Alba, Carolina, Ararat, Erhan, Raby, Benjamin A., Lu, Bao, Paschini, Margherita, Bronson, Roderick T., and Kim, Carla F.
- Published
- 2022
- Full Text
- View/download PDF
20. Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma
- Author
-
Li, Nina, Mirzakhani, Hoomann, Kiefer, Alexander, Koelle, Julia, Vuorinen, Tytti, Rauh, Manfred, Yang, Zuqin, Krammer, Susanne, Xepapadaki, Paraskevi, Lewandowska-Polak, Anna, Lukkarinen, Heikki, Zhang, Nan, Stanic, Barbara, Zimmermann, Theodor, Kowalski, Marek L., Jartti, Tuomas, Bachert, Claus, Akdis, Mübeccel, Papadopoulos, Nikolaos G., Raby, Benjamin A., Weiss, Scott T., and Finotto, Susetta
- Published
- 2021
- Full Text
- View/download PDF
21. A meta-analysis of genome-wide association studies of asthma in Puerto Ricans
- Author
-
Yan, Qi, Brehm, John, Pino-Yanes, Maria, Forno, Erick, Lin, Jerome, Oh, Sam S, Acosta-Perez, Edna, Laurie, Cathy C, Cloutier, Michelle M, Raby, Benjamin A, Stilp, Adrienne M, Sofer, Tamar, Hu, Donglei, Huntsman, Scott, Eng, Celeste S, Conomos, Matthew P, Rastogi, Deepa, Rice, Kenneth, Canino, Glorisa, Chen, Wei, Barr, R Graham, Burchard, Esteban G, and Celedón, Juan C
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Lung ,Human Genome ,Clinical Research ,Genetics ,Asthma ,2.1 Biological and endogenous factors ,Aetiology ,Respiratory ,Adolescent ,Adult ,Child ,Chromosomes ,Human ,Pair 17 ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Hispanic or Latino ,Humans ,Linkage Disequilibrium ,Logistic Models ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,Puerto Rico ,Young Adult ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
Puerto Ricans are disproportionately affected with asthma in the USA. In this study, we aim to identify genetic variants that confer susceptibility to asthma in Puerto Ricans.We conducted a meta-analysis of genome-wide association studies (GWAS) of asthma in Puerto Ricans, including participants from: the Genetics of Asthma in Latino Americans (GALA) I-II, the Hartford-Puerto Rico Study and the Hispanic Community Health Study. Moreover, we examined whether susceptibility loci identified in previous meta-analyses of GWAS are associated with asthma in Puerto Ricans.The only locus to achieve genome-wide significance was chromosome 17q21, as evidenced by our top single nucleotide polymorphism (SNP), rs907092 (OR 0.71, p=1.2×10-12) at IKZF3 Similar to results in non-Puerto Ricans, SNPs in genes in the same linkage disequilibrium block as IKZF3 (e.g. ZPBP2, ORMDL3 and GSDMB) were significantly associated with asthma in Puerto Ricans. With regard to results from a meta-analysis in Europeans, we replicated findings for rs2305480 at GSDMB, but not for SNPs in any other genes. On the other hand, we replicated results from a meta-analysis of North American populations for SNPs at IL1RL1, TSLP and GSDMB but not for IL33Our findings suggest that common variants on chromosome 17q21 have the greatest effects on asthma in Puerto Ricans.
- Published
- 2017
22. Network study of nasal transcriptome profiles reveals master regulator genes of asthma
- Author
-
Do, Anh N., Chun, Yoojin, Grishina, Galina, Grishin, Alexander, Rogers, Angela J., Raby, Benjamin A., Weiss, Scott T., Vicencio, Alfin, Schadt, Eric E., and Bunyavanich, Supinda
- Published
- 2021
- Full Text
- View/download PDF
23. Abstract 10848: Adar1 Mediated Rna Editing Contributes to Vascular Remodeling
- Author
-
Kim, Hyunbum, Liu, Yu, Klouda, Timothy, Schumacher, Valerie A, Thompson, Alfred A, Wu, Joseph C, Li, Jin Billy, Raby, Benjamin, and Yuan, Ke
- Published
- 2022
- Full Text
- View/download PDF
24. Involvement of fine particulate matter exposure with gene expression pathways in breast tumor and adjacent-normal breast tissue
- Author
-
DuPré, Natalie C., Heng, Yujing J., Raby, Benjamin A., Glass, Kimberly, Hart, Jaime E., Chu, Jen-hwa, Askew, Catherine, Eliassen, A. Heather, Hankinson, Susan E., Kraft, Peter, Laden, Francine, and Tamimi, Rulla M.
- Published
- 2020
- Full Text
- View/download PDF
25. Pulmonary Eosinophilic Granulomatosis with Polyangiitis Has IgG4 Plasma Cells and Immunoregulatory Features
- Author
-
Dong, Zachary M., Lin, Edwin, Wechsler, Michael E., Weller, Peter F., Klion, Amy D., Bochner, Bruce S., Delker, Don A., Hazel, Mark W., Fairfax, Keke, Khoury, Paneez, Akuthota, Praveen, Merkel, Peter A., Dyer, Anne-Marie, Langford, Carol, Specks, Ulrich, Gleich, Gerald J., Chinchilli, Vernon M., Raby, Benjamin, Yandell, Mark, and Clayton, Frederic
- Published
- 2020
- Full Text
- View/download PDF
26. GSDMB/ORMDL3 Rare/Common Variants Are Associated with Inhaled Corticosteroid Response among Children with Asthma
- Author
-
Voorhies, Kirsten, primary, Mohammed, Akram, additional, Chinthala, Lokesh, additional, Kong, Sek Won, additional, Lee, In-Hee, additional, Kho, Alvin T., additional, McGeachie, Michael, additional, Mandl, Kenneth D., additional, Raby, Benjamin, additional, Hayes, Melanie, additional, Davis, Robert L., additional, Wu, Ann Chen, additional, and Lutz, Sharon M., additional
- Published
- 2024
- Full Text
- View/download PDF
27. Is prophylaxis with palivizumab in very low birth weight infants (VLBWIs) associated with improved lung function at early school age?
- Author
-
Makrinioti, Heidi, primary and Raby, Benjamin A., additional
- Published
- 2024
- Full Text
- View/download PDF
28. The Asthma Risk Gene, GSDMB, Promotes Mitochondrial DNA-induced ISGs Expression
- Author
-
Liu, Tao, primary, Hecker, Julian, additional, Liu, Siqi, additional, Rui, Xianliang, additional, Boyer, Nathan, additional, Wang, Jennifer, additional, Yu, Yuzhen, additional, Zhang, Yihan, additional, Mou, Hongmei, additional, Guillermo Gomez-Escobar, Luis, additional, M.K. Choi, Augustine, additional, A. Raby, Benjamin, additional, T. Weiss, Scott, additional, and Zhou, Xiaobo, additional
- Published
- 2024
- Full Text
- View/download PDF
29. Pharmacogenetic investigation of efficacy response to mepolizumab in eosinophilic granulomatosis with polyangiitis
- Author
-
Condreay, Lynn D., Parham, Laura R., Qu, Xiaoyan A., Steinfeld, Jonathan, Wechsler, Michael E., Raby, Benjamin A., Yancey, Steven W., and Ghosh, Soumitra
- Published
- 2020
- Full Text
- View/download PDF
30. A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics
- Author
-
Baudrand, Rene, Goodarzi, Mark O, Vaidya, Anand, Underwood, Patricia C, Williams, Jonathan S, Jeunemaitre, Xavier, Hopkins, Paul N, Brown, Nancy, Raby, Benjamin A, Lasky-Su, Jessica, Adler, Gail K, Cui, Jinrui, Guo, Xiuqing, Taylor, Kent D, Chen, Yii-Der I, Xiang, Anny, Raffel, Leslie J, Buchanan, Thomas A, Rotter, Jerome I, Williams, Gordon H, and Pojoga, Luminita H
- Subjects
Nutrition ,Obesity ,Diabetes ,Clinical Research ,Cardiovascular ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Metabolic and endocrine ,Adult ,Caveolin 1 ,Cohort Studies ,Female ,Genotype ,Hispanic or Latino ,Humans ,Male ,Metabolic Syndrome ,Middle Aged ,Whites ,Metabolic syndrome ,Insulin resistance ,Cardiovascular risk ,White People ,Clinical Sciences ,Endocrinology & Metabolism - Abstract
Context and objectiveWe examined whether a prevalent caveolin-1 gene (CAV1) variant, previously related to insulin resistance, is associated with metabolic syndrome (MetS).Patients and methodsWe included subjects genotyped for the CAV1 variant rs926198 from two cohorts: 735 Caucasians from the HyperPATH multicenter study, and 810 Hispanic participants from the HTN-IR cohort.ResultsMinor allele carriers from HyperPATH cohort (57% of subjects) had higher Framingham risk scores, higher odds of diabetes (10.7% vs 5.7%, p=0.016), insulin resistance (44.3% vs 35.1%, p=0.022), low HDL (49.3% vs 39.6%, p=0.018) and MetS (33% vs 20.5%, p
- Published
- 2015
31. Stress and Bronchodilator Response in Children with Asthma
- Author
-
Brehm, John M, Ramratnam, Sima K, Tse, Sze Man, Croteau-Chonka, Damien C, Pino-Yanes, Maria, Rosas-Salazar, Christian, Litonjua, Augusto A, Raby, Benjamin A, Boutaoui, Nadia, Han, Yueh-Ying, Chen, Wei, Forno, Erick, Marsland, Anna L, Nugent, Nicole R, Eng, Celeste, Colón-Semidey, Angel, Alvarez, María, Acosta-Pérez, Edna, Spear, Melissa L, Martinez, Fernando D, Avila, Lydiana, Weiss, Scott T, Soto-Quiros, Manuel, Ober, Carole, Nicolae, Dan L, Barnes, Kathleen C, Lemanske, Robert F, Strunk, Robert C, Liu, Andrew, London, Stephanie J, Gilliland, Frank, Sleiman, Patrick, March, Michael, Hakonarson, Hakon, Duan, Qing Ling, Kolls, Jay K, Fritz, Gregory K, Hu, Donglei, Fani, Negar, Stevens, Jennifer S, Almli, Lynn M, Burchard, Esteban G, Shin, Jaemin, McQuaid, Elizabeth L, Ressler, Kerry, Canino, Glorisa, and Celedón, Juan C
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Pediatric ,Asthma ,Behavioral and Social Science ,Clinical Research ,Mental Health ,Lung ,Genetics ,Aetiology ,2.3 Psychological ,social and economic factors ,Respiratory ,Good Health and Well Being ,Adolescent ,Anxiety ,Bronchodilator Agents ,Case-Control Studies ,Child ,Cross-Sectional Studies ,Down-Regulation ,Female ,Genetic Markers ,Genotype ,Humans ,Linear Models ,Male ,Multivariate Analysis ,Polymorphism ,Single Nucleotide ,Puerto Rico ,Receptors ,Adrenergic ,beta-2 ,Receptors ,Pituitary Adenylate Cyclase-Activating Polypeptide ,Type I ,Rhode Island ,Risk Factors ,Stress ,Psychological ,Treatment Outcome ,asthma ,Puerto Ricans ,bronchodilator response ,stress ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
RationaleStress is associated with asthma morbidity in Puerto Ricans (PRs), who have reduced bronchodilator response (BDR).ObjectivesTo examine whether stress and/or a gene regulating anxiety (ADCYAP1R1) is associated with BDR in PR and non-PR children with asthma.MethodsThis was a cross-sectional study of stress and BDR (percent change in FEV1 after BD) in 234 PRs ages 9-14 years with asthma. We assessed child stress using the Checklist of Children's Distress Symptoms, and maternal stress using the Perceived Stress Scale. Replication analyses were conducted in two cohorts. Polymorphisms in ADCYAP1R1 were genotyped in our study and six replication studies. Multivariable models of stress and BDR were adjusted for age, sex, income, environmental tobacco smoke, and use of inhaled corticosteroids.Measurements and main resultsHigh child stress was associated with reduced BDR in three cohorts. PR children who were highly stressed (upper quartile, Checklist of Children's Distress Symptoms) and whose mothers had high stress (upper quartile, Perceived Stress Scale) had a BDR that was 10.2% (95% confidence interval, 6.1-14.2%) lower than children who had neither high stress nor a highly stressed mother. A polymorphism in ADCYAP1R1 (rs34548976) was associated with reduced BDR. This single-nucleotide polymorphism is associated with reduced expression of the gene for the β2-adrenergic receptor (ADRB2) in CD4(+) lymphocytes of subjects with asthma, and it affects brain connectivity of the amygdala and the insula (a biomarker of anxiety).ConclusionsHigh child stress and an ADCYAP1R1 single-nucleotide polymorphism are associated with reduced BDR in children with asthma. This is likely caused by down-regulation of ADRB2 in highly stressed children.
- Published
- 2015
32. Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos
- Author
-
Pino-Yanes, Maria, Gignoux, Christopher R, Galanter, Joshua M, Levin, Albert M, Campbell, Catarina D, Eng, Celeste, Huntsman, Scott, Nishimura, Katherine K, Gourraud, Pierre-Antoine, Mohajeri, Kiana, O'Roak, Brian J, Hu, Donglei, Mathias, Rasika A, Nguyen, Elizabeth A, Roth, Lindsey A, Padhukasahasram, Badri, Moreno-Estrada, Andres, Sandoval, Karla, Winkler, Cheryl A, Lurmann, Fred, Davis, Adam, Farber, Harold J, Meade, Kelley, Avila, Pedro C, Serebrisky, Denise, Chapela, Rocio, Ford, Jean G, Lenoir, Michael A, Thyne, Shannon M, Brigino-Buenaventura, Emerita, Borrell, Luisa N, Rodriguez-Cintron, William, Sen, Saunak, Kumar, Rajesh, Rodriguez-Santana, Jose R, Bustamante, Carlos D, Martinez, Fernando D, Raby, Benjamin A, Weiss, Scott T, Nicolae, Dan L, Ober, Carole, Meyers, Deborah A, Bleecker, Eugene R, Mack, Steven J, Hernandez, Ryan D, Eichler, Evan E, Barnes, Kathleen C, Williams, L Keoki, Torgerson, Dara G, and Burchard, Esteban G
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,Human Genome ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Adolescent ,Adult ,Black or African American ,Child ,Chromosome Mapping ,Chromosomes ,Human ,Pair 14 ,DNA-Binding Proteins ,Female ,Genetic Loci ,Genome ,Human ,Genome-Wide Association Study ,Genotype ,HLA-DQ alpha-Chains ,Hispanic or Latino ,Humans ,Immunoglobulin E ,Male ,Polymorphism ,Single Nucleotide ,Transcription Factors ,White People ,IgE ,genome-wide association study ,admixture mapping ,allergy ,asthma ,next-generation sequencing ,Latinos ,Hispanics ,minority populations ,Allergy - Abstract
BackgroundIgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders.ObjectiveWe sought to identify genetic variants associated with IgE levels in Latinos.MethodsWe performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies.ResultsWe confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of a polymorphism in the zinc finger protein 365 gene (ZNF365) with total IgE levels (rs200076616, P = 2.3 × 10(-8)). We next identified 4 admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) at which local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower IgE levels (P = 4.95 × 10(-8)). All but 22q13.1 were replicated in an independent sample of Latinos, and 2 of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified 6 genome-wide significant single nucleotide polymorphisms in Latinos, 2 of which replicated in European Americans. Another single nucleotide polymorphism was peak-wide significant within 14q23.2 in African Americans (rs1741099, P = 3.7 × 10(-6)) and replicated in non-African American samples (P = .011).ConclusionWe confirmed genetic associations at 6 genes and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse multiethnic populations to uncover novel loci associated with total IgE levels.
- Published
- 2015
33. Author Correction: Discovering the genes mediating the interactions between chronic respiratory diseases in the human interactome
- Author
-
Maiorino, Enrico, Baek, Seung Han, Guo, Feng, Zhou, Xiaobo, Kothari, Parul H., Silverman, Edwin K., Barabási, Albert-László, Weiss, Scott T., Raby, Benjamin A., and Sharma, Amitabh
- Published
- 2021
- Full Text
- View/download PDF
34. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma
- Author
-
Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, Zoellner, Sebastian, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Levin, Albert M., Gui, Hongsheng, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Weiss, Scott T., and Lasky-Su, Jessica A.
- Published
- 2019
- Full Text
- View/download PDF
35. A trial of type 12 purinergic (P2Y12) receptor inhibition with prasugrel identifies a potentially distinct endotype of patients with aspirin-exacerbated respiratory disease
- Author
-
Laidlaw, Tanya M., Cahill, Katherine N., Cardet, Juan Carlos, Murphy, Katherine, Cui, Jing, Dioneda, Brittney, Kothari, Parul, Raby, Benjamin A., Israel, Elliot, and Boyce, Joshua A.
- Published
- 2019
- Full Text
- View/download PDF
36. Genome-wide interaction studies reveal sex-specific asthma risk alleles
- Author
-
Myers, Rachel A, Scott, Nicole M, Gauderman, W James, Qiu, Weiliang, Mathias, Rasika A, Romieu, Isabelle, Levin, Albert M, Pino-Yanes, Maria, Graves, Penelope E, Villarreal, Albino Barraza, Beaty, Terri H, Carey, Vincent J, Croteau-Chonka, Damien C, del Rio Navarro, Blanca, Edlund, Christopher, Hernandez-Cadena, Leticia, Navarro-Olivos, Efrain, Padhukasahasram, Badri, Salam, Muhammad T, Torgerson, Dara G, Van den Berg, David J, Vora, Hita, Bleecker, Eugene R, Meyers, Deborah A, Williams, L Keoki, Martinez, Fernando D, Burchard, Esteban G, Barnes, Kathleen C, Gilliland, Frank D, Weiss, Scott T, London, Stephanie J, Raby, Benjamin A, Ober, Carole, Nicolae, Dan L, Santana, Jose Rodriguez, Cintron, William Rodriguez, Chapela, Rocio, Ford, Jean, Thyne, Shannon, Avila, Pedro C, Monge, Juan Jose Sienra, Boorgula, Meher, Cheadle, Chris, Eng, Celeste S, Kiley, J, Banks-Schlegel, S, and Gan, W
- Subjects
Biological Sciences ,Genetics ,Clinical Research ,Human Genome ,Lung ,Prevention ,Asthma ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Respiratory ,Alleles ,Chromosome Mapping ,Female ,Gene Expression Regulation ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Odds Ratio ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Racial Groups ,Reproducibility of Results ,Sex Factors ,GRAAD ,Continental Population Groups ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Asthma is a complex disease with sex-specific differences in prevalence. Candidate gene studies have suggested that genotype-by-sex interaction effects on asthma risk exist, but this has not yet been explored at a genome-wide level. We aimed to identify sex-specific asthma risk alleles by performing a genome-wide scan for genotype-by-sex interactions in the ethnically diverse participants in the EVE Asthma Genetics Consortium. We performed male- and female-specific genome-wide association studies in 2653 male asthma cases, 2566 female asthma cases and 3830 non-asthma controls from European American, African American, African Caribbean and Latino populations. Association tests were conducted in each study sample, and the results were combined in ancestry-specific and cross-ancestry meta-analyses. Six sex-specific asthma risk loci had P-values < 1 × 10(-6), of which two were male specific and four were female specific; all were ancestry specific. The most significant sex-specific association in European Americans was at the interferon regulatory factor 1 (IRF1) locus on 5q31.1. We also identify a Latino female-specific association in RAP1GAP2. Both of these loci included single-nucleotide polymorphisms that are known expression quantitative trait loci and have been associated with asthma in independent studies. The IRF1 locus is a strong candidate region for male-specific asthma susceptibility due to the association and validation we demonstrate here, the known role of IRF1 in asthma-relevant immune pathways and prior reports of sex-specific differences in interferon responses.
- Published
- 2014
37. Detecting and dissecting signaling crosstalk via the multilayer network integration of signaling and regulatory interactions
- Author
-
Martini, Leonardo, primary, Baek, Seung Han, additional, Lo, Ian, additional, Raby, Benjamin A, additional, Silverman, Edwin K, additional, Weiss, Scott T, additional, Glass, Kimberly, additional, and Halu, Arda, additional
- Published
- 2023
- Full Text
- View/download PDF
38. Rheumatoid arthritis and risk of chronic obstructive pulmonary disease or asthma among women: A marginal structural model analysis in the Nurses’ Health Study
- Author
-
Sparks, Jeffrey A., Lin, Tzu-Chieh, Camargo, Carlos A., Jr, Barbhaiya, Medha, Tedeschi, Sara K., Costenbader, Karen H., Raby, Benjamin A., Choi, Hyon K., and Karlson, Elizabeth W.
- Published
- 2018
- Full Text
- View/download PDF
39. A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations
- Author
-
Levin, Albert M, Mathias, Rasika A, Huang, Lili, Roth, Lindsey A, Daley, Denise, Myers, Rachel A, Himes, Blanca E, Romieu, Isabelle, Yang, Mao, Eng, Celeste, Park, Julie E, Zoratti, Karla, Gignoux, Christopher R, Torgerson, Dara G, Galanter, Joshua M, Huntsman, Scott, Nguyen, Elizabeth A, Becker, Allan B, Chan-Yeung, Moira, Kozyrskyj, Anita L, Kwok, Pui-Yan, Gilliland, Frank D, Gauderman, W James, Bleecker, Eugene R, Raby, Benjamin A, Meyers, Deborah A, London, Stephanie J, Martinez, Fernando D, Weiss, Scott T, Burchard, Esteban G, Nicolae, Dan L, Ober, Carole, Barnes, Kathleen C, and Williams, L Keoki
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Lung ,Human Genome ,Clinical Research ,Genetics ,Asthma ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Adolescent ,Adult ,Black or African American ,Aged ,Aged ,80 and over ,Canada ,Case-Control Studies ,Child ,Child ,Preschool ,Female ,Genome-Wide Association Study ,HLA-DQ beta-Chains ,Hispanic or Latino ,Humans ,Immunoglobulin E ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,United States ,White People ,Meta-analysis ,genome-wide association study ,total IgE ,race-ethnicity ,continental population groups ,Allergy - Abstract
BackgroundIgE is both a marker and mediator of allergic inflammation. Despite reported differences in serum total IgE levels by race-ethnicity, African American and Latino subjects have not been well represented in genetic studies of total IgE.ObjectiveWe sought to identify the genetic predictors of serum total IgE levels.MethodsWe used genome-wide association data from 4292 subjects (2469 African Americans, 1564 European Americans, and 259 Latinos) in the EVE Asthma Genetics Consortium. Tests for association were performed within each cohort by race-ethnic group (ie, African American, Latino, and European American) and asthma status. The resulting P values were meta-analyzed, accounting for sample size and direction of effect. Top single nucleotide polymorphism associations from the meta-analysis were reassessed in 6 additional cohorts comprising 5767 subjects.ResultsWe identified 10 unique regions in which the combined association statistic was associated with total serum IgE levels (P
- Published
- 2013
40. Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans
- Author
-
Myers, Rachel A, Himes, Blanca E, Gignoux, Christopher R, Yang, James J, Gauderman, W James, Rebordosa, Cristina, Xie, Jianming, Torgerson, Dara G, Levin, Albert M, Baurley, James, Graves, Penelope E, Mathias, Rasika A, Romieu, Isabelle, Roth, Lindsey A, Conti, David, Avila, Lydiana, Eng, Celeste, Vora, Hita, LeNoir, Michael A, Soto-Quiros, Manuel, Liu, Jinghua, Celedón, Juan C, Galanter, Joshua M, Farber, Harold J, Kumar, Rajesh, Avila, Pedro C, Meade, Kelley, Serebrisky, Denise, Thyne, Shannon, Rodriguez-Cintron, William, Rodriguez-Santana, Jose R, Borrell, Luisa N, Lemanske, Robert F, Bleecker, Eugene R, Meyers, Deborah A, London, Stephanie J, Barnes, Kathleen C, Raby, Benjamin A, Martinez, Fernando D, Gilliland, Frank D, Williams, L Keoki, Burchard, Esteban G, Weiss, Scott T, Nicolae, Dan L, and Ober, Carole
- Subjects
Genetics ,Asthma ,Lung ,Human Genome ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Black or African American ,Chromosomes ,Human ,Pair 19 ,DNA Mutational Analysis ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Hispanic or Latino ,Humans ,Kallikreins ,Meta-Analysis as Topic ,Polymorphism ,Single Nucleotide ,Prostate-Specific Antigen ,Risk Factors ,United States ,White People ,genetic risk factors ,meta-analysis ,KLK3 ,Immunology ,Allergy - Abstract
BackgroundGenome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk.ObjectivesWe aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis.MethodsWe selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis.ResultsTwo novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos.ConclusionsThis extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations.
- Published
- 2012
41. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.
- Author
-
Torgerson, Dara G, Ampleford, Elizabeth J, Chiu, Grace Y, Gauderman, W James, Gignoux, Christopher R, Graves, Penelope E, Himes, Blanca E, Levin, Albert M, Mathias, Rasika A, Hancock, Dana B, Baurley, James W, Eng, Celeste, Stern, Debra A, Celedón, Juan C, Rafaels, Nicholas, Capurso, Daniel, Conti, David V, Roth, Lindsey A, Soto-Quiros, Manuel, Togias, Alkis, Li, Xingnan, Myers, Rachel A, Romieu, Isabelle, Van Den Berg, David J, Hu, Donglei, Hansel, Nadia N, Hernandez, Ryan D, Israel, Elliott, Salam, Muhammad T, Galanter, Joshua, Avila, Pedro C, Avila, Lydiana, Rodriquez-Santana, Jose R, Chapela, Rocio, Rodriguez-Cintron, William, Diette, Gregory B, Adkinson, N Franklin, Abel, Rebekah A, Ross, Kevin D, Shi, Min, Faruque, Mezbah U, Dunston, Georgia M, Watson, Harold R, Mantese, Vito J, Ezurum, Serpil C, Liang, Liming, Ruczinski, Ingo, Ford, Jean G, Huntsman, Scott, Chung, Kian Fan, Vora, Hita, Li, Xia, Calhoun, William J, Castro, Mario, Sienra-Monge, Juan J, del Rio-Navarro, Blanca, Deichmann, Klaus A, Heinzmann, Andrea, Wenzel, Sally E, Busse, William W, Gern, James E, Lemanske, Robert F, Beaty, Terri H, Bleecker, Eugene R, Raby, Benjamin A, Meyers, Deborah A, London, Stephanie J, Mexico City Childhood Asthma Study (MCAAS), Gilliland, Frank D, Children's Health Study (CHS) and HARBORS study, Burchard, Esteban G, Genetics of Asthma in Latino Americans (GALA) Study, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Asthma, Genes & Environments (SAGE), Martinez, Fernando D, Childhood Asthma Research and Education (CARE) Network, Weiss, Scott T, Childhood Asthma Management Program (CAMP), Williams, L Keoki, Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE), Barnes, Kathleen C, Genetic Research on Asthma in African Diaspora (GRAAD) Study, Ober, Carole, and Nicolae, Dan L
- Subjects
Mexico City Childhood Asthma Study ,Children's Health Study (CHS) and HARBORS study ,Genetics of Asthma in Latino Americans (GALA) Study ,Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans ,Asthma ,Genes & Environments ,Childhood Asthma Research and Education (CARE) Network ,Childhood Asthma Management Program ,Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity ,Genetic Research on Asthma in African Diaspora (GRAAD) Study ,Humans ,Asthma ,Genetic Predisposition to Disease ,Risk ,African Americans ,European Continental Ancestry Group ,Hispanic Americans ,Caribbean Region ,North America ,Genome-Wide Association Study ,Genetic Loci ,Genetics of Asthma in Latino Americans (GALA) Study ,Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans ,Genes & Environments ,Developmental Biology ,Biological Sciences ,Medical and Health Sciences - Abstract
Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.
- Published
- 2011
42. Genetic-Epigenetic Interactions in Asthma Revealed by a Genome-Wide Gene-Centric Search
- Author
-
Kogan, Vladimir, Millstein, Joshua, London, Stephanie J., Ober, Carole, White, Steven R., Naureckas, Edward T., Gauderman, W. James, Jackson, Daniel J., Barraza-Villarreal, Albino, Romieu, Isabelle, Raby, Benjamin A., and Breton, Carrie V.
- Published
- 2017
43. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children.
- Author
-
Hancock, Dana B, Romieu, Isabelle, Shi, Min, Sienra-Monge, Juan-Jose, Wu, Hao, Chiu, Grace Y, Li, Huiling, del Rio-Navarro, Blanca Estela, Willis-Owen, Saffron AG, Weiss, Scott T, Raby, Benjamin A, Gao, Hong, Eng, Celeste, Chapela, Rocio, Burchard, Esteban G, Tang, Hua, Sullivan, Patrick F, and London, Stephanie J
- Subjects
Chromosomes ,Human ,Pair 9 ,Humans ,Asthma ,Genetic Predisposition to Disease ,Case-Control Studies ,Adolescent ,Adult ,Child ,Mexico ,Female ,Male ,Genome-Wide Association Study ,Young Adult ,Chromosomes ,Human ,Pair 9 ,Genetics ,Developmental Biology - Abstract
Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.
- Published
- 2009
44. Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial
- Author
-
Ringshausen, Felix C, primary, Shapiro, Adam J, additional, Nielsen, Kim G, additional, Mazurek, Henryk, additional, Pifferi, Massimo, additional, Donn, Karl H, additional, van der Eerden, Menno M, additional, Loebinger, Michael R, additional, Zariwala, Maimoona A, additional, Leigh, Margaret W, additional, Knowles, Michael R, additional, Ferkol, Thomas W, additional, Ringshausen, Felix C, additional, Ferkol, Jr, Thomas W, additional, Brown, Trey, additional, Carroll, Mary, additional, Church, Nina, additional, Couluris, Marisa, additional, Davis, Stephanie D, additional, Dell, Sharon D, additional, Di Cicco, Maria E, additional, Di Mango, Angela, additional, Escobar, Hugo, additional, Griffiths, Anne, additional, Haver, Kenan, additional, Hornick, Douglas, additional, Johnson, Christopher, additional, Milla, Carlos E, additional, O'Donnell, Anne, additional, Pink, Isabell, additional, Pogorzelski, Andrzej, additional, Prickett, Michelle, additional, Raby, Benjamin A, additional, Rosenfeld, Margaret, additional, Saba, Thomas G, additional, Sandvik, Rikke Mulvad, additional, Sagel, Scott D, additional, Salathe, Matthias, additional, Simmons, Ashley E, additional, Solomon, George M, additional, Sommerburg, Olaf, additional, Soussi, Najwa, additional, Strausbaugh, Steven D, additional, Sullivan, Kelli M, additional, and Werner, Claudius, additional
- Published
- 2023
- Full Text
- View/download PDF
45. A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities
- Author
-
Moll, Matthew, primary, Peljto, Anna L., additional, Kim, John S., additional, Xu, Hanfei, additional, Debban, Catherine L., additional, Chen, Xianfeng, additional, Menon, Aravind, additional, Putman, Rachel K, additional, Ghosh, Auyon J, additional, Saferali, Aabida, additional, Nishino, Mizuki, additional, Hatabu, Hiroto, additional, Hobbs, Brian D., additional, Hecker, Julian, additional, McDermott, Gregory, additional, Sparks, Jeffrey A., additional, Wain, Louise V, additional, Allen, Richard J, additional, Tobin, Martin D, additional, Raby, Benjamin A, additional, Chun, Sung, additional, Silverman, Edwin K, additional, Zamora, Ana C., additional, Ortega, Victor E, additional, Garcia, Christine K, additional, Barr, R Graham, additional, Bleecker, Eugene R, additional, Meyers, Deborah A, additional, Kaner, Robert J, additional, Rich, Stephen S., additional, Manichaikul, Ani, additional, Rotter, Jerome I, additional, Dupuis, Josée, additional, O'Connor, George T, additional, Fingerlin, Tasha E, additional, Hunninghake, Gary M, additional, Schwartz, David A, additional, and Cho, Michael H, additional
- Published
- 2023
- Full Text
- View/download PDF
46. Discovering the genes mediating the interactions between chronic respiratory diseases in the human interactome
- Author
-
Maiorino, Enrico, Baek, Seung Han, Guo, Feng, Zhou, Xiaobo, Kothari, Parul H., Silverman, Edwin K., Barabási, Albert-László, Weiss, Scott T., Raby, Benjamin A., and Sharma, Amitabh
- Published
- 2020
- Full Text
- View/download PDF
47. Asthma severity, nature or nurture: genetic determinants
- Author
-
Raby, Benjamin A.
- Published
- 2019
- Full Text
- View/download PDF
48. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks
- Author
-
Demenais, Florence, Margaritte-Jeannin, Patricia, Barnes, Kathleen C., Cookson, William O. C., Altmüller, Janine, Ang, Wei, Barr, R. Graham, Beaty, Terri H., Becker, Allan B., Beilby, John, Bisgaard, Hans, Bjornsdottir, Unnur Steina, Bleecker, Eugene, Bønnelykke, Klaus, Boomsma, Dorret I., Bouzigon, Emmanuelle, Brightling, Christopher E., Brossard, Myriam, Brusselle, Guy G., Burchard, Esteban, Burkart, Kristin M., Bush, Andrew, Chan-Yeung, Moira, Chung, Kian Fan, Couto Alves, Alexessander, Curtin, John A., Custovic, Adnan, Daley, Denise, de Jongste, Johan C., Del-Rio-Navarro, Blanca E., Donohue, Kathleen M., Duijts, Liesbeth, Eng, Celeste, Eriksson, Johan G., Farrall, Martin, Fedorova, Yuliya, Feenstra, Bjarke, Ferreira, Manuel A., Freidin, Maxim B., Gajdos, Zofia, Gauderman, Jim, Gehring, Ulrike, Geller, Frank, Genuneit, Jon, Gharib, Sina A., Gilliland, Frank, Granell, Raquel, Graves, Penelope E., Gudbjartsson, Daniel F., Haahtela, Tari, Heckbert, Susan R., Heederik, Dick, Heinrich, Joachim, Heliövaara, Markku, Henderson, John, Himes, Blanca E., Hirose, Hiroshi, Hirschhorn, Joel N., Hofman, Albert, Holt, Patrick, Hottenga, Jouke, Hudson, Thomas J., Hui, Jennie, Imboden, Medea, Ivanov, Vladimir, Jaddoe, Vincent W. V., James, Alan, Janson, Christer, Jarvelin, Marjo-Riitta, Jarvis, Deborah, Jones, Graham, Jonsdottir, Ingileif, Jousilahti, Pekka, Kabesch, Michael, Kähönen, Mika, Kantor, David B., Karunas, Alexandra S., Khusnutdinova, Elza, Koppelman, Gerard H., Kozyrskyj, Anita L., Kreiner, Eskil, Kubo, Michiaki, Kumar, Rajesh, Kumar, Ashish, Kuokkanen, Mikko, Lahousse, Lies, Laitinen, Tarja, Laprise, Catherine, Lathrop, Mark, Lau, Susanne, Lee, Young-Ae, Lehtimäki, Terho, Letort, Sébastien, Levin, Albert M., Li, Guo, Liang, Liming, Loehr, Laura R., London, Stephanie J., Loth, Daan W., Manichaikul, Ani, Marenholz, Ingo, Martinez, Fernando J., Matheson, Melanie C., Mathias, Rasika A., Matsumoto, Kenji, Mbarek, Hamdi, McArdle, Wendy L., Melbye, Mads, Melén, Erik, Meyers, Deborah, Michel, Sven, Mohamdi, Hamida, Musk, Arthur W., Myers, Rachel A., Nieuwenhuis, Maartje A. E., Noguchi, Emiko, O’Connor, George T., Ogorodova, Ludmila M., Palmer, Cameron D., Palotie, Aarno, Park, Julie E., Pennell, Craig E., Pershagen, Göran, Polonikov, Alexey, Postma, Dirkje S., Probst-Hensch, Nicole, Puzyrev, Valery P., Raby, Benjamin A., Raitakari, Olli T., Ramasamy, Adaikalavan, Rich, Stephen S., Robertson, Colin F., Romieu, Isabelle, Salam, Muhammad T., Salomaa, Veikko, Schlünssen, Vivi, Scott, Robert, Selivanova, Polina A., Sigsgaard, Torben, Simpson, Angela, Siroux, Valérie, Smith, Lewis J., Solodilova, Maria, Standl, Marie, Stefansson, Kari, Strachan, David P., Stricker, Bruno H., Takahashi, Atsushi, Thompson, Philip J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiesler, Carla M. T., Torgerson, Dara G., Tsunoda, Tatsuhiko, Uitterlinden, André G., van der Valk, Ralf J. P., Vaysse, Amaury, Vedantam, Sailaja, von Berg, Andrea, von Mutius, Erika, Vonk, Judith M., Waage, Johannes, Wareham, Nick J., Weiss, Scott T., White, Wendy B., Wickman, Magnus, Widén, Elisabeth, Willemsen, Gonneke, Williams, L. Keoki, Wouters, Inge M., Yang, James J., Zhao, Jing Hua, Moffatt, Miriam F., Ober, Carole, and Nicolae, Dan L.
- Published
- 2018
- Full Text
- View/download PDF
49. ACDC: a general approach for detecting phenotype or exposure associated co-expression
- Author
-
Queen, Katelyn, primary, Nguyen, My-Nhi, additional, Gilliland, Frank D., additional, Chun, Sung, additional, Raby, Benjamin A., additional, and Millstein, Joshua, additional
- Published
- 2023
- Full Text
- View/download PDF
50. Gene expression profiling of asthma phenotypes demonstrates molecular signatures of atopy and asthma control
- Author
-
Howrylak, Judie A., Moll, Matthew, Weiss, Scott T., Raby, Benjamin A., Wu, Wei, and Xing, Eric P.
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.