Genome-wide screen for asthma in Puerto Ricans: evidence for association with 5q23 region

Springer Science and Business Media LLC - Tập 123 - Trang 455-468 - 2008
Shweta Choudhry1,2,3, Margaret Taub4, Rui Mei5, José Rodriguez-Santana6, William Rodriguez-Cintron7, Mark D. Shriver8, Elad Ziv1,3, Neil J. Risch1,9,10, Esteban González Burchard1,2,3,11,10
1Institute for Human Genetics, University of California, San Francisco, USA
2UCSF/Lung Biology Center, University of California, San Francisco, San Francisco, USA
3Department of Medicine, University of California, San Francisco, USA
4Department of Biostatistics, University of California, Berkeley, USA
5Affymetrix Inc., Santa Clara, USA
6Centro de Neumologia Pediatrica, CSP, San Juan, USA
7Veterans Caribbean Health Care System, The University of Puerto Rico School of Medicine, San Juan, USA
8Department of Anthropology, Pennsylvania State University, University Park, USA
9Department of Epidemiology and Biostatistics, University of California, San Francisco, USA
10Division of Research, Kaiser Permanente, Oakland, USA
11Department of Biopharmaceutical Sciences, University of California, San Francisco, USA

Tóm tắt

While the number of success stories for mapping genes associated with complex diseases using genome-wide association approaches is growing, there is still much work to be done in developing methods for such studies when the samples are collected from a population, which may not be homogeneous. Here we report the first genome-wide association study to identify genes associated with asthma in an admixed population. We genotyped 96 Puerto Rican moderate to severe asthma cases and 88 controls as well as 109 samples representing Puerto Rico’s founding populations using the Affymetrix GeneChip Human Mapping 100K array sets. The data from samples representing Puerto Rico’s founding populations was used to identify ancestry informative markers for admixture mapping analyses. In addition, a genome-wide association analysis using logistic regression was performed on the data. Although neither admixture mapping nor regression analysis gave any significant association with asthma after correction for multiple testing, an overlap analysis using the top scoring SNPs from different methods suggested chromosomal regions 5q23.3 and 13q13.3 as potential regions harboring genes for asthma in Puerto Ricans. The validation analysis of these two regions in 284 Puerto Rican asthma trios gave significant association for the 5q23.3 region. Our results provide strong evidence that the previously linked 5q23 region is associated with asthma in Puerto Ricans. The detection of causative variants in this region will require fine mapping and functional validation.

Tài liệu tham khảo

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