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Significant linkage to airway responsiveness on chromosome 12q24 in families of children with asthma in Costa Rica

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Abstract

Although asthma is a major public health problem in certain Hispanic subgroups in the United States and Latin America, only one genome scan for asthma has included Hispanic individuals. Because of small sample size, that study had limited statistical power to detect linkage to asthma and its intermediate phenotypes in Hispanic participants. To identify genomic regions that contain susceptibility genes for asthma and airway responsiveness in an isolated Hispanic population living in the Central Valley of Costa Rica, we conducted a genome-wide linkage analysis of asthma (n = 638) and airway responsiveness (n = 488) in members of eight large pedigrees of Costa Rican children with asthma. Nonparametric multipoint linkage analysis of asthma was conducted by the NPL-PAIR allele-sharing statistic, and variance component models were used for the multipoint linkage analysis of airway responsiveness as a quantitative phenotype. All linkage analyses were repeated after exclusion of the phenotypic data of former and current smokers. Chromosome 12q showed some evidence of linkage to asthma, particularly in nonsmokers (P < 0.01). Among nonsmokers, there was suggestive evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 2.33 at 146 cM). After genotyping 18 additional short-tandem repeat markers on chromosome 12q, there was significant evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 3.79 at 144 cM), with a relatively narrow 1.5-LOD unit support interval for the observed linkage peak (142–147 cM). Our results suggest that chromosome 12q24.31 contains a locus (or loci) that influence a critical intermediate phenotype of asthma (airway responsiveness) in Costa Ricans.

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Acknowledgments

The authors would like to thank the study families for their enthusiastic participation, the members of our field team in Costa Rica (Ligia Sanabria, Jenny Vega, Marvin Corrales, Adriana Gonzalez, Raquel Boza, Joaquín Acuña, Laura Rojas, Ana Castillo, Gabriela Ivankovich, Marcia Solano, Herminia Solano, and Heliberto Mena), all of the staff who were involved in genotyping efforts at McGill University and the Genome Quebec Innovation Centre (Genevieve Geneau, Alexandre Belisle, Corinne Darmon-Zwaig, Frederick Robidoux, David Roquis, and Yannick Renaud) and the Channing Laboratory (Benedict Bodota, Vimala Chompupong, and Elizabeth Bevilacqua), and Mr. John Ziniti and Ms. Nancy K. Voynow for help with preparation of the manuscript.

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Authors and Affiliations

  1. Channing Laboratory (Department of Medicine) and Respiratory Disorders Program, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA, 02115, USA

    Juan C. Celedón, Stephen L. Lake, Catherine Liang, Craig P. Hersh, Jody S. Sylvia, Barbara J. Klanderman, Edwin K. Silverman & Scott T. Weiss

  2. Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Juan C. Celedón

  3. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Juan C. Celedón, Stephen L. Lake, Craig P. Hersh, Edwin K. Silverman & Scott T. Weiss

  4. Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica

    Manuel E. Soto-Quiros, Lydiana Avila, Eduardo Fournier & Mitzi Spesny

  5. McGill University and Genome Quebec Innovation Centre, Montreal, Canada

    Thomas J. Hudson & Andrei Verner

  6. Department of Psychiatry, University of California at Los Angeles, Los Angeles, CA, USA

    Nelson B. Freimer

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  1. Juan C. Celedón
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  2. Manuel E. Soto-Quiros
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  3. Lydiana Avila
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Correspondence to Juan C. Celedón.

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This work was supported by grants HL04370 and HL66289 from the National Institutes of Health.

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Celedón, J.C., Soto-Quiros, M.E., Avila, L. et al. Significant linkage to airway responsiveness on chromosome 12q24 in families of children with asthma in Costa Rica . Hum Genet 120, 691–699 (2007). https://doi.org/10.1007/s00439-006-0255-5

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