Biological Sciences Division
Published November 14, 2012 | Version v1
Journal article Open

Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe)

Creators

  • 1. Brigham and Women's Hospital
  • 2. Vanderbilt University
  • 3. Harvard University
  • 4. Mount Sinai Hospital
  • 5. Jackson State University
  • 6. University of Mississippi Medical Center
  • 7. University of Washington
  • 8. Boston University
  • 9. Sir Charles Gairdner Hospital
  • 10. University of Chicago
  • 11. Case Western Reserve University
  • 12. Northwestern University

Description

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study.

Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×10−6. Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts.

Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.

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Additional details

Identifiers

DOI
10.1371/journal.pone.0048836
Other
oai:uchicago.tind.io:10377

Funding

National Heart, Lung, and Blood Institute
HHSN268201100005C
National Heart, Lung, and Blood Institute
HHSN268201100006C
National Heart, Lung, and Blood Institute
HHSN268201100007C
National Heart, Lung, and Blood Institute
HHSN268201100008C
National Heart, Lung, and Blood Institute
HHSN268201100009C
National Heart, Lung, and Blood Institute
HHSN268201100010C
National Heart, Lung, and Blood Institute
HHSN268201100011C
National Heart, Lung, and Blood Institute
HHSN268201100012C
National Heart, Lung, and Blood Institute
R01HL087641
National Heart, Lung, and Blood Institute
R01HL59367
National Heart, Lung, and Blood Institute
R01HL086694
National Human Genome Research Institute
U01HG004402
National Institutes of Health
HHSN268200625226C
National Institutes of Health
UL1RR025005
National Cancer Institute
CA116867
National Heart, Lung, and Blood Institute
HL081385
National Heart, Lung, and Blood Institute
HL46380
National Heart, Lung, and Blood Institute
N01-HC-85239
National Heart, Lung, and Blood Institute
N01-HC-85079
National Heart, Lung, and Blood Institute
N01-HC-85086
National Heart, Lung, and Blood Institute
N01-HC-35129
National Heart, Lung, and Blood Institute
N01 HC-15103
National Heart, Lung, and Blood Institute
N01 HC-55222
National Heart, Lung, and Blood Institute
N01-HC-75150
National Heart, Lung, and Blood Institute
N01-HC-45133
National Heart, Lung, and Blood Institute
HL080295
National Institute of Neurological Disorders and Stroke
National Institute of Aging
AG-023629
National Institute of Aging
AG-15928
National Institute of Aging
AG-20098
National Institute of Aging
AG-027058
National Heart, Lung, and Blood Institute
HL94092
Sir Charles Gairdner and Hollywood Private Hospital Research Foundations
State Health Research Advisory Council of Western Australia
Western Australian Sleep Disorders Research Institute
University of Western Australia
Centre for Genetic Epidemiology and Biostatistics

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Public Health Sciences