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10. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

Author

Torgerson, Dara G, Ampleford, Elizabeth J, Chiu, Grace Y, Gauderman, W James, Gignoux, Christopher R, Graves, Penelope E, Himes, Blanca E, Levin, Albert M, Mathias, Rasika A, Hancock, Dana B, Baurley, James W, Eng, Celeste, Stern, Debra A, Celedón, Juan C, Rafaels, Nicholas, Capurso, Daniel, Conti, David V, Roth, Lindsey A, Soto-Quiros, Manuel, Togias, Alkis, Li, Xingnan, Myers, Rachel A, Romieu, Isabelle, Van Den Berg, David J, Hu, Donglei, Hansel, Nadia N, Hernandez, Ryan D, Israel, Elliott, Salam, Muhammad T, Galanter, Joshua, Avila, Pedro C, Avila, Lydiana, Rodriquez-Santana, Jose R, Chapela, Rocio, Rodriguez-Cintron, William, Diette, Gregory B, Adkinson, N Franklin, Abel, Rebekah A, Ross, Kevin D, Shi, Min, Faruque, Mezbah U, Dunston, Georgia M, Watson, Harold R, Mantese, Vito J, Ezurum, Serpil C, Liang, Liming, Ruczinski, Ingo, Ford, Jean G, Huntsman, Scott, Chung, Kian Fan, Vora, Hita, Li, Xia, Calhoun, William J, Castro, Mario, Sienra-Monge, Juan J, del Rio-Navarro, Blanca, Deichmann, Klaus A, Heinzmann, Andrea, Wenzel, Sally E, Busse, William W, Gern, James E, Lemanske, Robert F, Beaty, Terri H, Bleecker, Eugene R, Raby, Benjamin A, Meyers, Deborah A, London, Stephanie J, Mexico City Childhood Asthma Study (MCAAS), Gilliland, Frank D, Children's Health Study (CHS) and HARBORS study, Burchard, Esteban G, Genetics of Asthma in Latino Americans (GALA) Study, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Asthma, Genes & Environments (SAGE), Martinez, Fernando D, Childhood Asthma Research and Education (CARE) Network, Weiss, Scott T, Childhood Asthma Management Program (CAMP), Williams, L Keoki, Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE), Barnes, Kathleen C, Genetic Research on Asthma in African Diaspora (GRAAD) Study, Ober, Carole, and Nicolae, Dan L

Subjects
Risk, European Continental Ancestry Group, Childhood Asthma Management Program, Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity, Medical and Health Sciences, White People, Genetics, Humans, Genetic Predisposition to Disease, Childhood Asthma Research and Education (CARE) Network, Mexico City Childhood Asthma Study, Lung, Genes & Environments, Genetic Research on Asthma in African Diaspora (GRAAD) Study, African Americans, Human Genome, Hispanic or Latino, Biological Sciences, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Asthma, respiratory tract diseases, Genetics of Asthma in Latino Americans (GALA) Study, Black or African American, Caribbean Region, Genetic Loci, Children's Health Study (CHS) and HARBORS study, North America, Respiratory, Hispanic Americans, Genome-Wide Association Study, Developmental Biology
Abstract

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

Published
2011

11. TSLP Polymorphisms are Associated with Asthma in a Sex-Specific Fashion

Author

Hunninghake, Gary M., Soto-Quirós, Manuel E., Avila, Lydiana, Kim, Hong P., Lasky-Su, Jessica, Rafaels, Nicholas, Ruczinski, Ingo, Beaty, Terry H., Mathias, Rasika A., Barnes, Kathleen C., Wilk, Jemma B., O’Connor, George T., Gauderman, W. James, Vora, Hita, Baurley, James W., Gilliland, Frank, Liang, Catherine, Sylvia, Jody S., Klanderman, Barbara J., Sharma, Sunita S., Himes, Blanca E., Bossley, Cara J., Israel, Elliot, Raby, Benjamin A., Bush, Andrew, Choi, Augustine M., Weiss, Scott T., and Celedón, Juan C.

Subjects
Costa Rica, Male, Sex Characteristics, Genotype, Black People, Hispanic or Latino, Polymorphism, Single Nucleotide, Article, Asthma, White People, Cohort Studies, Thymic Stromal Lymphopoietin, Risk Factors, Cytokines, Humans, Female, Genetic Predisposition to Disease, Child, Genome-Wide Association Study
Abstract

Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion.We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS).Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS.TSLP variants are associated with asthma in a sex-specific fashion.

Published
2010

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