Joshua M Galanter1, Christopher R Gignoux2, Dara G Torgerson3, Lindsey A Roth3, Celeste Eng3, Sam S Oh3, Elizabeth A Nguyen4, Katherine A Drake2, Scott Huntsman3, Donglei Hu3, Saunak Sen5, Adam Davis6, Harold J Farber7, Pedro C Avila8, Emerita Brigino-Buenaventura9, Michael A LeNoir10, Kelley Meade6, Denise Serebrisky11, Luisa N Borrell12, William Rodríguez-Cintrón13, Andres Moreno Estrada14, Karla Sandoval Mendoza14, Cheryl A Winkler15, William Klitz16, Isabelle Romieu17, Stephanie J London18, Frank Gilliland19, Fernando Martinez20, Carlos Bustamante14, L Keoki Williams21, Rajesh Kumar22, José R Rodríguez-Santana23, Esteban G Burchard24. 1. Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif. Electronic address: joshua.galanter@ucsf.edu. 2. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif. 3. Department of Medicine, University of California, San Francisco, Calif. 4. School of Medicine, St Louis University, St Louis, Mo. 5. Department of Epidemiology & Biostatistics, University of California, San Francisco, Calif. 6. Children's Hospital and Research Center Oakland, Oakland, Calif. 7. Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex. 8. Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill. 9. Department of Allergy & Immunology, Kaiser Permanente-Vallejo Medical Center, Vallejo, Calif. 10. Bay Area Pediatrics, Oakland, Calif. 11. Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, NY. 12. Department of Health Sciences, Graduate Program in Public Health, Lehman College, City University of New York, Bronx, NY. 13. Veterans Caribbean Health Care System, San Juan, Puerto Rico. 14. Department of Genetics, Stanford University, Stanford, Calif. 15. Frederick National Laboratory for Cancer Research, National Institutes of Health, Frederick, Md. 16. School of Public Health, University of California, Berkeley, Calif. 17. International Agency for Research on Cancer, Lyon, France. 18. National Institute of Environmental Health Sciences, National Institutes of Health, Dept of Health and Human Services, Research Triangle Park, NC. 19. Department of Preventive Medicine, University of Southern California, Los Angeles, Calif. 20. Department of Pediatrics, University of Arizona, Tucson, Ariz. 21. Department of Internal Medicine, Henry Ford Health System, Detroit, Mich. 22. Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill. 23. Centro de Neumologia Pediatrica, San Juan, Puerto Rico. 24. Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
Abstract
BACKGROUND: Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent. OBJECTIVE: We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. METHODS: Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. RESULTS: We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. CONCLUSIONS: Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21. Published by Mosby, Inc.
BACKGROUND:Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent. OBJECTIVE: We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. METHODS: Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. RESULTS: We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. CONCLUSIONS: Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21. Published by Mosby, Inc.
Entities:
Keywords:
17q21; 6p21; Asthma; Latinos; admixture mapping; genome-wide association study; local ancestry
Authors: Yael Baran; Bogdan Pasaniuc; Sriram Sankararaman; Dara G Torgerson; Christopher Gignoux; Celeste Eng; William Rodriguez-Cintron; Rocio Chapela; Jean G Ford; Pedro C Avila; Jose Rodriguez-Santana; Esteban Gonzàlez Burchard; Eran Halperin Journal: Bioinformatics Date: 2012-04-11 Impact factor: 6.937
Authors: Matthew L Freedman; Christopher A Haiman; Nick Patterson; Gavin J McDonald; Arti Tandon; Alicja Waliszewska; Kathryn Penney; Robert G Steen; Kristin Ardlie; Esther M John; Ingrid Oakley-Girvan; Alice S Whittemore; Kathleen A Cooney; Sue A Ingles; David Altshuler; Brian E Henderson; David Reich Journal: Proc Natl Acad Sci U S A Date: 2006-08-31 Impact factor: 11.205
Authors: Lucia A Hindorff; Praveen Sethupathy; Heather A Junkins; Erin M Ramos; Jayashri P Mehta; Francis S Collins; Teri A Manolio Journal: Proc Natl Acad Sci U S A Date: 2009-05-27 Impact factor: 11.205
Authors: Prescott G Woodruff; Barmak Modrek; David F Choy; Guiquan Jia; Alexander R Abbas; Almut Ellwanger; Laura L Koth; Joseph R Arron; John V Fahy Journal: Am J Respir Crit Care Med Date: 2009-05-29 Impact factor: 21.405
Authors: Gonneke Willemsen; Toos C E M van Beijsterveldt; Caroline G C M van Baal; Dirkje Postma; Dorret I Boomsma Journal: Twin Res Hum Genet Date: 2008-04 Impact factor: 1.587
Authors: J Apostolakis; M Toumbis; K Konstantopoulos; D Kamaroulias; J Anagnostakis; V Georgoulias; P Fessas; J Zervas Journal: Respir Med Date: 1996-04 Impact factor: 3.415
Authors: James Y Zou; Danny S Park; Esteban G Burchard; Dara G Torgerson; Maria Pino-Yanes; Yun S Song; Sriram Sankararaman; Eran Halperin; Noah Zaitlen Journal: Proc Natl Acad Sci U S A Date: 2015-10-19 Impact factor: 11.205
Authors: Natalia Hernandez-Pacheco; Carlos Flores; Sam S Oh; Esteban G Burchard; Maria Pino-Yanes Journal: Curr Allergy Asthma Rep Date: 2016-07 Impact factor: 4.806
Authors: Ivana V Yang; Brent S Pedersen; Andrew H Liu; George T O'Connor; Dinesh Pillai; Meyer Kattan; Rana Tawil Misiak; Rebecca Gruchalla; Stanley J Szefler; Gurjit K Khurana Hershey; Carolyn Kercsmar; Adam Richards; Allen D Stevens; Christena A Kolakowski; Melanie Makhija; Christine A Sorkness; Rebecca Z Krouse; Cynthia Visness; Elizabeth J Davidson; Corinne E Hennessy; Richard J Martin; Alkis Togias; William W Busse; David A Schwartz Journal: J Allergy Clin Immunol Date: 2016-10-13 Impact factor: 10.793
Authors: Eunice Y Lee; Angel C Y Mak; Donglei Hu; Satria Sajuthi; Marquitta J White; Kevin L Keys; Walter Eckalbar; Luke Bonser; Scott Huntsman; Cydney Urbanek; Celeste Eng; Deepti Jain; Gonçalo Abecasis; Hyun M Kang; Soren Germer; Michael C Zody; Deborah A Nickerson; David Erle; Elad Ziv; Jose Rodriguez-Santana; Max A Seibold; Esteban G Burchard Journal: Am J Respir Crit Care Med Date: 2020-10-01 Impact factor: 21.405
Authors: Maria Pino-Yanes; Christopher R Gignoux; Joshua M Galanter; Albert M Levin; Catarina D Campbell; Celeste Eng; Scott Huntsman; Katherine K Nishimura; Pierre-Antoine Gourraud; Kiana Mohajeri; Brian J O'Roak; Donglei Hu; Rasika A Mathias; Elizabeth A Nguyen; Lindsey A Roth; Badri Padhukasahasram; Andres Moreno-Estrada; Karla Sandoval; Cheryl A Winkler; Fred Lurmann; Adam Davis; Harold J Farber; Kelley Meade; Pedro C Avila; Denise Serebrisky; Rocio Chapela; Jean G Ford; Michael A Lenoir; Shannon M Thyne; Emerita Brigino-Buenaventura; Luisa N Borrell; William Rodriguez-Cintron; Saunak Sen; Rajesh Kumar; Jose R Rodriguez-Santana; Carlos D Bustamante; Fernando D Martinez; Benjamin A Raby; Scott T Weiss; Dan L Nicolae; Carole Ober; Deborah A Meyers; Eugene R Bleecker; Steven J Mack; Ryan D Hernandez; Evan E Eichler; Kathleen C Barnes; L Keoki Williams; Dara G Torgerson; Esteban G Burchard Journal: J Allergy Clin Immunol Date: 2014-12-06 Impact factor: 10.793
Authors: Berta Almoguera; Lyam Vazquez; Frank Mentch; John Connolly; Jennifer A Pacheco; Agnes S Sundaresan; Peggy L Peissig; James G Linneman; Catherine A McCarty; David Crosslin; David S Carrell; Todd Lingren; Bahram Namjou-Khales; John B Harley; Eric Larson; Gail P Jarvik; Murray Brilliant; Marc S Williams; Iftikhar J Kullo; Erik B Hysinger; Patrick M A Sleiman; Hakon Hakonarson Journal: Am J Respir Crit Care Med Date: 2017-02-15 Impact factor: 21.405