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
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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.
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