Human Genetics

, Volume 131, Issue 9, pp 1495–1505 | Cite as

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

  • Jessica Lasky-Su
  • Nancy Lange
  • John M. Brehm
  • Amy Damask
  • Manuel Soto-Quiros
  • Lydiana Avila
  • Juan C. Celedón
  • Glorisa Canino
  • Michelle M. Cloutier
  • Bruce W. Hollis
  • Scott T. Weiss
  • Augusto A. Litonjua
Original Investigation

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.

Supplementary material

439_2012_1185_MOESM1_ESM.docx (35 kb)
Supplementary material 1 (DOCX 35 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Jessica Lasky-Su
    • 1
    • 2
  • Nancy Lange
    • 1
    • 2
    • 3
  • John M. Brehm
    • 4
  • Amy Damask
    • 5
  • Manuel Soto-Quiros
    • 6
  • Lydiana Avila
    • 6
  • Juan C. Celedón
    • 4
  • Glorisa Canino
    • 7
  • Michelle M. Cloutier
    • 8
  • Bruce W. Hollis
    • 9
  • Scott T. Weiss
    • 1
    • 2
    • 10
  • Augusto A. Litonjua
    • 1
    • 2
    • 3
  1. 1.Channing Laboratory, Department of MedicineBrigham and Women’s HospitalBostonUSA
  2. 2.Harvard Medical SchoolBostonUSA
  3. 3.Division of Pulmonary and Critical Care Medicine, Department of MedicineBrigham and Women’s HospitalBostonUSA
  4. 4.Division of Pediatric Pulmonary Medicine, Allergy and ImmunologyChildren’s Hospital of Pittsburgh of UPMCPittsburghUSA
  5. 5.Novartis Institutes for Biomedical ResearchCambridgeUSA
  6. 6.Division of Pediatric PulmonologyHospital Nacional de NiñosSan JoséCosta Rica
  7. 7.Behavioral Sciences InstituteUniversity of Puerto RicoSan JuanUSA
  8. 8.University of Connecticut Health CenterFarmingtonUSA
  9. 9.Darby Children’s Research InstituteMedical University of South CarolinaCharlestonUSA
  10. 10.Department of MedicineCenter for Genomic Medicine, Brigham and Women’s HospitalBostonUSA

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