Original Investigation

Human Genetics

, Volume 131, Issue 9, pp 1495-1505

First online:

Genome-wide association analysis of circulating vitamin D levels in children with asthma

  • Jessica Lasky-SuAffiliated withChanning Laboratory, Department of Medicine, Brigham and Women’s HospitalHarvard Medical School
  • , Nancy LangeAffiliated withChanning Laboratory, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital
  • , John M. BrehmAffiliated withDivision of Pediatric Pulmonary Medicine, Allergy and Immunology, Children’s Hospital of Pittsburgh of UPMC
  • , Amy DamaskAffiliated withNovartis Institutes for Biomedical Research
  • , Manuel Soto-QuirosAffiliated withDivision of Pediatric Pulmonology, Hospital Nacional de Niños
  • , Lydiana AvilaAffiliated withDivision of Pediatric Pulmonology, Hospital Nacional de Niños
  • , Juan C. CeledónAffiliated withDivision of Pediatric Pulmonary Medicine, Allergy and Immunology, Children’s Hospital of Pittsburgh of UPMC
  • , Glorisa CaninoAffiliated withBehavioral Sciences Institute, University of Puerto Rico
  • , Michelle M. CloutierAffiliated withUniversity of Connecticut Health Center
    • , Bruce W. HollisAffiliated withDarby Children’s Research Institute, Medical University of South Carolina
    • , Scott T. WeissAffiliated withChanning Laboratory, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolDepartment of Medicine, Center for Genomic Medicine, Brigham and Women’s Hospital
    • , Augusto A. LitonjuaAffiliated withChanning Laboratory, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital Email author 

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Abstract

Vitamin D deficiency is becoming more apparent in many populations. Genetic factors may play a role in the maintenance of vitamin D levels. The objective of this study was to perform a genome-wide analysis (GWAS) of vitamin D levels, including replication of prior GWAS results. We measured 25-hydroxyvitamin D (25(OH)D) levels in serum collected at the time of enrollment and at year 4 in 572 Caucasian children with asthma, who were part of a multi-center clinical trial, the Childhood Asthma Management Program. Replication was performed in a second cohort of 592 asthmatics from Costa Rica and a third cohort of 516 Puerto Rican asthmatics. In addition, we attempted replication of three SNPs that were previously identified in a large GWAS of Caucasian individuals. The setting included data from a clinical trial of childhood asthmatics and two cohorts of asthmatics recruited for genetic studies of asthma. The main outcome measure was circulating 25(OH)D levels. The 25(OH)D levels at the two time-points were only modestly correlated with each other (intraclass correlation coefficient = 0.33) in the CAMP population. We identified SNPs that were nominally associated with 25(OH)D levels at two time-points in CAMP, and replicated four SNPs in the Costa Rican cohort: rs11002969, rs163221, rs1678849, and rs4864976. However, these SNPs were not significantly associated with 25(OH)D levels in a third population of Puerto Rican asthmatics. We were able to replicate the SNP with the strongest effect, previously reported in a large GWAS: rs2282679 (GC), and we were able to replicate another SNP, rs10741657 (CYP2R1), to a lesser degree. We were able to replicate two of three prior significant findings in a GWAS of 25(OH)D levels. Other SNPs may be additionally associated with 25(OH)D levels in certain populations.