- 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;
- Ober, Carole
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.