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Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study

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Abstract

Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 × 10−7) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

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Acknowledgments

The authors acknowledge the patients, families, recruiters, health care providers, and community clinics for their participation. In particular, the authors thank Sandra Salazar for her support as the SAGE II study coordinator. The authors also acknowledge the Lowell Science Research Program, Lowell High School, San Francisco, CA. This work was supported in part by the Sandler Foundation, the American Asthma Foundation, the RWJF Amos Medical Faculty Development Program, and the National Institutes of Health (ES015794 and MD006902).

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    Authors and Affiliations

    1. Department of Medicine, University of California, San Francisco, UCSF Box 2911, San Francisco, CA, 94143-2911, USA

      Marquitta J. White, O. Risse-Adams, P. Goddard, M. G. Contreras, J. Adams, D. Hu, C. Eng, S. S. Oh, K. Bibbins-Domingo & E. G. Burchard

    2. Lowell Science Research Program, Lowell High School, San Francisco, CA, USA

      O. Risse-Adams

    3. SF BUILD, San Francisco State University, San Francisco, CA, USA

      M. G. Contreras

    4. Children’s Hospital and Research Center Oakland, Oakland, CA, USA

      A. Davis & K. Meade

    5. Department of Allergy and Immunology, Kaiser Permanente Vallejo Medical Center, Vallejo, CA, USA

      E. Brigino-Buenaventura

    6. Bay Area Pediatrics, Oakland, CA, USA

      M. A. LeNoir

    7. Research Unit, Hospital Universitario N.S. de Candelaria, Tenerife, Spain

      M. Pino-Yanes

    8. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain

      M. Pino-Yanes

    9. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA

      E. G. Burchard

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    Corresponding author

    Correspondence to Marquitta J. White.

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    Conflict of interest

    EGB has been funded by the National Institutes of Health (R01ES015794 and P60-MD006902), the Sandler Foundation, the RWJF Amos Medical Faculty Development Award, and the American Asthma Foundation. MPY has received honoraria for speaking at symposium from Affymetrix. The rest of the authors report no conflicts of interest in this work.

    Additional information

    Marquitta J. White and O. Risse-Adams contributed equally to this work.

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    Post-hoc Power Calculations for Detectable Effect Sizes in the SAGE II population. (GIF 22 kb)

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    White, M.J., Risse-Adams, O., Goddard, P. et al. Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study. Immunogenetics 68, 391–400 (2016). https://doi.org/10.1007/s00251-016-0914-1

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