1. Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans
- Author
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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
Biomedical and Clinical Sciences ,Immunology ,Prevention ,Clinical Research ,Genetics ,Human Genome ,Asthma ,Lung ,2.1 Biological and endogenous factors ,Respiratory ,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 ,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