Title: Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans.
Authors: 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 Jr, 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; Ober, Carole
Published In J Allergy Clin Immunol, (2012 Dec)
Abstract: 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.We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis.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.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.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.
PubMed ID: 23040885
MeSH Terms: African Americans; Asthma/epidemiology*; Asthma/genetics*; Asthma/immunology; Chromosomes, Human, Pair 19/genetics*; DNA Mutational Analysis; European Continental Ancestry Group; Genetic Loci/immunology; Genetic Predisposition to Disease; Genome-Wide Association Study; Hispanic Americans; Humans; Kallikreins/genetics*; Meta-Analysis as Topic; Polymorphism, Single Nucleotide; Prostate-Specific Antigen/genetics*; Risk Factors; United States