Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans

Myers, R. A.; Himes, B. E.; Gignoux, C. R.; Yang, J. J.; Gauderman, W. J.; Rebordosa, C.; Xie, J.; Torgerson, D. G.; Levin, A. M.; Baurley, J.; Graves, P. E.; Mathias, R. A.; Romieu, I.; Roth, L. A.; Conti, D.; Avila, L.; Eng, C.; Vora, H.; LeNoir, M. A.; Soto-Quiros, M.; Liu, J.; Celedon, J. C.; Galanter, J. M.; Farber, H. J.; Kumar, R.; Avila, P. C.; Meade, K.; Serebrisky, D.; Thyne, S.; Rodriguez-Cintron, W.; Rodriguez-Santana, J. R.; Borrell, L. N.; Lemanske, R. F., Jr.; Bleecker, E. R.; Meyers, D. A.; London, S. J.; Barnes, K. C.; Raby, B. A.; Martinez, F. D.; Gilliland, F. D.; Williams, L. K.; Burchard, E. G.; Weiss, S. T.; Nicolae, D. L.; Ober, C.

J Allergy Clin Immunol. 2012 Oct 9; 130(6):1294-301


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.

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