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Novel recessive locus for body mass index in childhood asthma
  1. Sanghun Lee1,
  2. Jessica Lasky-Su2,
  3. Sungho Won3,
  4. Cecelia Laurie4,
  5. Juan Carlos Celedón5,
  6. Christoph Lange6,
  7. Scott Weiss2,
  8. Julian Hecker2
  1. 1 Department of Medical Consilience, Division of Medicine, Graduate School, Dankook University—Jukjeon Campus, Yongin, South Korea
  2. 2 Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3 Department of Public Health Science, Seoul National University, Gwanak-gu, South Korea
  4. 4 Department of Biostatistics, University of Washington, Seattle, Washington, USA
  5. 5 Division of Pediatric Pulmonary Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA
  6. 6 Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
  1. Correspondence to Dr Sanghun Lee, Dankook University—Jukjeon Campus, Yongin, Korea (the Republic of); shlee92{at}dankook.ac.kr

Abstract

Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in FTO. In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in LOC102724122 and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses.

  • paediatric asthma
  • asthma genetics

https://doi.org/10.1136/thoraxjnl-2020-215742

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    Footnotes

    • Correction notice This article has been corrected since it was published Online First. Table 1 has been corrected.

    • Contributors SHL, CLange and JH conceptualised and designed the project, performed statistical analyses and interpretation, and drafted the manuscript. SW, CLaurie, JCC, JL-S and SW assisted in data preparation and the analyses as well as manuscript preparation. All authors contributed to the relevant sections and approved the final manuscript.

    • Funding This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1F1A01072033) and the Industrial Core Technology Development Program (20000134) funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea); Cure Alzheimer’s Fund; the National Human Genome Research Institute (R01HG008976, 2U01HG008685); and the National Heart, Lung, and Blood Institute (P01HL132825, U01HL089856, U01HL089897, P01HL120839).

    • Competing interests JCC has received research materials from Merck and GSK (inhaled steroids) and Pharmavite (vitamin D and placebo capsules), in order to provide medications free of cost to participants in NIH-funded studies, unrelated to the current work.

    • Provenance and peer review Not commissioned; externally peer reviewed.