Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 130, Issue 6, Pages 1294-1301Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2012.07.054
Keywords
Asthma; genetic risk factors; meta-analysis; KLK3
Categories
Funding
- National Heart, Lung, and Blood Institute (NHLBI)
- National Institutes of Health (NIH)
- NIH
- UpToDate
- EMD China
- American Academy of Pediatrics
- University of California
- NHLBI
- Pharmaxis
- Michigan Public Health Institute
- Allegheny General Hospital
- West Allegheny Health Systems, Inc
- California Chapter 4
- AAP
- Colorado Allergy Society
- Pennsylvania Allergy and Asthma Association
- Harvard Pilgrim Health
- California Society of Allergy
- NYC Allergy Society
- World Allergy Organization
- American College of Chest Physicians
- American Academy of Allergy, Asthma, Immunology
- Elsevier
- Abbott
- Merck
- National Institute of Allergy and Infectious Diseases
- Office of the Director, National Institutes of Health (NIH)
- National Heart, Lung, and Blood Institute [HL087665, HL070831, HL072414, HL049596, HL064307, HL064313, HL075419, HL65899, HL083069, HL066289, HL101543, HL101651, HL079055, HL087699, HL49612, HL075417, HL04266, HL072433, HL061768, HL076647, HL087680, HL078885, HL088133, HL87665]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK064695]
- National Institutes of Environmental Health Sciences [ES09606, ES018176, ES015903, ES007048, ES009581, R826708, RD831861, ES011627, ES015794]
- Division of Intramural Research [Z01 ES049019]
- National Center for Research Resources [RR03048, RR00188]
- Environmental Protection Agency [83213901, R-826724]
- American Asthma Foundation
- Fund for Henry Ford Hospital
- Mary Beryl Patch Turnbull Scholar Program
- Flight Attendant Medical Research Institute (FAMRI)
- Robert Wood Johnson Foundation (RWJF)
- Amos Medical Faculty Development Award
- Sandler Foundation
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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. (J Allergy Clin Immunol 2012;130:1294-301.)
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