Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study - 01/08/14
, Christopher R. Gignoux, MS b, Dara G. Torgerson, PhD a, Lindsey A. Roth, MA a, Celeste Eng, BS a, Sam S. Oh, MPH, PhD a, Elizabeth A. Nguyen, BS c, Katherine A. Drake, PhD b, Scott Huntsman, MS a, Donglei Hu, PhD a, Saunak Sen, PhD d, Adam Davis, MA, MPH e, Harold J. Farber, MD, MSPH f, Pedro C. Avila, MD g, Emerita Brigino-Buenaventura, MD h, Michael A. LeNoir, MD i, Kelley Meade, MD e, Denise Serebrisky, MD j, Luisa N. Borrell, DDS, PhD k, William Rodríguez-Cintrón, MD l, Andres Moreno Estrada, MD, PhD m, Karla Sandoval Mendoza, MS, PhD m, Cheryl A. Winkler, PhD n, William Klitz, PhD o, Isabelle Romieu, MD, MPH p, Stephanie J. London, MD, DrPh q, Frank Gilliland, MD, PhD r, Fernando Martinez, MD s, Carlos Bustamante, MA, PhD m, L. Keoki Williams, MD, MPH t, Rajesh Kumar, MD u, José R. Rodríguez-Santana, MD v, Esteban G. Burchard, MD, MPH a, bAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, Latinos, admixture mapping, genome-wide association study, local ancestry, 17q21, 6p21
Abbreviations used : GALA II, GWAS, OR, SNP
Plan
| Supported in part by the National Institutes of Health (NIH; R01 ES015794, R01 HL088133, M01 RR000083, R01 HL078885, R01 HL104608, P60 MD006902, U19 AI077439, and M01 RR00188) and ARRA grant RC2 HL101651. E.G.B. was supported in part through grants from the Flight Attendant Medical Research Institute (FAMRI), the Sandler Foundation, the American Asthma Foundation and NIH (K23 HL004464). J.M.G. was supported in part by NIH Training Grant T32 (GM007546) and career development awards from the NHLBI K23 (K23HL111636) and NCATS KL2 (KL2TR000143), as well as the Hewett Fellowship. C.R.G. was supported in part by NIH Training Grant T32 (GM007175) and the UCSF Chancellor’s Research Fellowship and Dissertation Year Fellowship. R.K. was supported with a career development award from the NHLBI (K23HL093023). H.J.F. was supported in part by the GCRC (RR00188). P.C.A. was supported in part by the Ernest S. Bazley Grant. S.J.L. was supported in part by the Division of Intramural Research, National Institute of Environmental Health Sciences (ZIA ES49019). This publication was supported by various institutes within the NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. |
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| Disclosure of potential conflict of interest: C. R. Gignoux has received a grant from the National Institutes of Health (NIH) and has stock/stock options with 23andMe. C. Eng, S. S. Oh, E. A. Nguyen, K. A. Drake, S. Sen, P. C. Avila, M. A. LeNoir, D. Serebrisky, L. N. Borrell, F. Gilliland, J. R. Rodriguez-Santana, and E. G. Burchard have received grants from the NIH. H. J. Farber has received a grant from the NIH, is the Associate Medical Director of Texas Children's Health Plan, has provided expert testimony in a malpractice case, has received payment for lectures from the American Academy of Pediatrics and Milestone Standard Consulting/Astra Zeneca, and is a medical journal editor for Mary Anne Liebert. E. Brigino-Buenaventura has received a grant, consulting fees, and travel support from the Sandler Foundation. K. Meade has received a grant from the University of California. F. Martinez has received research support from the NIH and has received travel support from Abbott and Merck. C. Bustamente has received research support from the NIH; is a member of the Scientific Advisory Boards for Personalis Inc and Ancestry.com; is a member of the Medical Advisory Board for Invitae; has consultant arrangements with 23andme.com, Etalon.com, and National Geographic; has patents filed by Stanford for DNA capture technology; and receives royalties from Personalis. L. K. Williams has received research support from the National Institute of Allergy and Infectious Disease; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Heart, Lung, and Blood Institute; and the NIH. R. Kumar has received grants from the National Heart, Lung, and Blood Institute and the NIH. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 134 - N° 2
P. 295-305 - août 2014 Retour au numéro
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