@article{961e154796794f41b2c18466075fbe84,
title = "Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans",
abstract = "Background: Genome-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. Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis. Methods: We 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. Results: Two 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. Conclusions: This 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.",
keywords = "Asthma, KLK3, genetic risk factors, meta-analysis",
author = "Myers, {Rachel A.} and Himes, {Blanca E.} and Gignoux, {Christopher R.} and Yang, {James J.} and Gauderman, {W. James} and Cristina Rebordosa and Jianming Xie and Torgerson, {Dara G.} and Levin, {Albert M.} and James Baurley and Graves, {Penelope E.} and Mathias, {Rasika A.} and Isabelle Romieu and Roth, {Lindsey A.} and David Conti and Lydiana Avila and Celeste Eng and Hita Vora and Lenoir, {Michael A.} and Manuel Soto-Quiros and Jinghua Liu and Celed{\'o}n, {Juan C.} and Farber, {Harold J.} and Rajesh Kumar and Avila, {Pedro C.} and Kelley Meade and Denise Serebrisky and Shannon Thyne and William Rodriguez-Cintron and Rodriguez-Santana, {Jose R.} and Borrell, {Luisa N.} and Lemanske, {Robert F.} and Bleecker, {Eugene R.} and Meyers, {Deborah A.} and London, {Stephanie J.} and Barnes, {Kathleen C.} and Raby, {Benjamin A.} and Martinez, {Fernando D.} and Gilliland, {Frank D.} and Williams, {L. Keoki} and Burchard, {Esteban G.} and Weiss, {Scott T.} and Nicolae, {Dan L.} and Carole Ober",
note = "Funding Information: Supported by grants from the Office of the Director, National Institutes of Health (NIH) to C.O. and D.L.N.; the National Heart, Lung, and Blood Institute ( HL101651 to C.O. and D.L.N.; HL087665 to D.L.N.; HL070831 , HL072414 , and HL049596 to C.O.; HL064307 and HL064313 to F.D.M.; HL075419 , HL65899 , HL083069 , HL066289 , HL087680 , HL101543 , and HL101651 to S.T.W.; HL079055 to L.K.W.; HL087699 , HL49612 , HL075417 , HL04266 , and HL072433 to K.C.B.; HL061768 and HL076647 to F.D.G.; HL087680 to W.J.G.; HL078885 and HL088133 to E.G.B.; and HL87665 to D.A.M.); the National Institutes of Allergy and Infectious Disease ( AI070503 to C.O.; AI079139 and AI061774 to L.K.W.; AI50024 , AI44840 , and AI41040 to K.C.B.; and AI077439 to E.G.B.); the National Institute of Diabetes and Digestive and Kidney Diseases to L.K.W. ( DK064695 ); the National Institutes of Environmental Health Sciences ( ES09606 , ES018176 , and ES015903 to K.C.B.; ES007048 , ES009581 , R826708 , RD831861 , and ES011627 to F.D.G.; ES015794 to E.G.B.; and the Division of Intramural Research, Z01 ES049019 to S.J.L.); the National Center for Research Resources ( RR03048 to K.C.B., RR00188 to H.J.F.); the Environmental Protection Agency ( 83213901 and R-826724 to K.C.B.); the American Asthma Foundation and the Fund for Henry Ford Hospital (to L.K.W.); Mary Beryl Patch Turnbull Scholar Program (to K.C.B.); and the Flight Attendant Medical Research Institute (FAMRI), Robert Wood Johnson Foundation (RWJF) Amos Medical Faculty Development Award, the American Asthma Foundation, and the Sandler Foundation (to E.G.B.). Funding Information: Disclosure of potential conflict of interest: C. R. Gignoux has received grants and travel support from the National Heart, Lung, and Blood Institute (NHLBI) and has stock/stock options in 23andMe, Inc. A. M. Levin has received grants and travel support from the National Institutes of Health (NIH) and is employed by Henry Ford Health System . R. A. Mathias has received grants from the NIH and the NHLBI and is employed by Johns Hopkins University . W. J. Gauderman, J. Baurley, L. A. Roth, D. Conti, R. Kumar, P. C. Avila, S. Thyne, J. R. Rodriguez-Santana, L. N. Borrell, F. D. Gilliland, E. G. Burchard, and D. L. Nicolae have received grants from the NIH. L. Avila has received payment for lectures, including service on speakers{\textquoteright} bureaus, from Merck Sharpe Dohme and AstraZeneca . M. A. LeNoir receives payment for lectures, including service on speakers{\textquoteright} bureaus, from Teva and GlaxoSmithKline . J. C. Celedon has received grants from the NIH, has consultant arrangements with Genentech , and receives royalties from UpToDate. H. J. Farber has received grants from the NIH, is employed by the Texas Children{\textquoteright}s Health Plan, has received payment for lectures from EMD China , has received payment for manuscript preparation from Web MD, has received travel expenses from the American Academy of Pediatrics, and has received honoraria for service as the Editor of Pediatric Allergy, Immunology, and Pulmonology from Mary Ann Liebert, Inc. D. Serebrisky has received grants from the NIH and has received payment for lectures, including service on speakers' bureaus, from Teva. W. Rodriguez-Cintron has received grants from the University of California, San Francisco . R. F. Lemankse, Jr has received travel support and fees for participation in review activities from the NIH; has consultant arrangements with Merck, Sepracor, SA Boney and Associates, LTD, GlaxoSmithKline, American Institute of Research, Genentech, Inc, Double Helix Development, Inc, and Boerhinger Ingelheim; is employed by the University of Wisconsin School of Medicine and Public Health; has received grants from the NHLBI and Pharmaxis ; has received payment for lectures, including service on speakers' bureaus, from the Michigan Public Health Institute, Allegheny General Hospital, the American Academy of Pediatrics, West Allegheny Health Systems, Inc, California Chapter 4, AAP, the Colorado Allergy Society, the Pennsylvania Allergy and Asthma Association, Harvard Pilgrim Health, the California Society of Allergy, the NYC Allergy Society, the World Allergy Organization, and the American College of Chest Physicians ; has received payment for manuscript preparation from the American Academy of Allergy, Asthma, & Immunology ; and has received royalties from Elsevier and UpToDate. D. A. Meyers has received grants from the NHLBI. K. C. Barnes has received grants from the NIH and the NHLBI; has board membership with Genentech; has consultant arrangements with Sanofi-Aventis and Sirius Genomics; is employed by Johns Hopkins University; and has received payments for lectures, including service on speakers' bureaus, from the “Evolution and Diseases of Modern Environments” Symposium, the American Academy of Allergy, Asthma, & Immunology, the Cincinnati CHMC Allergy Conference, and the 50th Annual Swineford Allergy Conference. B. A. Raby has received grants from the NIH and has received royalties from UpToDate, Inc . F. D. Martinez has consultant arrangements with MedImmune, has received grants from the NIH, has received payment for lectures, including service on speakers' bureaus, from Abbott and Merck, and has received travel expenses from Abbott and Merck. L. K. Williams has received grants from the National Institute of Allergy and Infectious Diseases and the NHLBI. C. Ober has received grants, travel support, fees for participation in review activities, and payment for lectures, including service on speakers{\textquoteright} bureaus, from the NIH. The rest of the authors declare that they have no relevant conflicts of interest. ",
year = "2012",
month = dec,
doi = "10.1016/j.jaci.2012.07.054",
language = "English (US)",
volume = "130",
pages = "1294--1301",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "6",
}