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.
Title
Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe)
Author
Patel, Sanjay R. : Brigham and Women's Hospital
Goodloe, Robert : Vanderbilt University
De, Gourab : Harvard University
Kowgier, Matthew : Mount Sinai Hospital
Weng, Jia : Brigham and Women's Hospital
Buxbaum, Sarah G. : Jackson State University
Cade, Brian : Brigham and Women's Hospital
Fulop, Tibor : University of Mississippi Medical Center
Gharib, Sina A. : University of Washington
Gottlieb, Daniel J. : Boston University
Hillman, David : Sir Charles Gairdner Hospital
Larkin, Emma K. : Vanderbilt University
Lauderdale, Diane S. : University of Chicago
Li, Li : Case Western Reserve University
Mukherjee, Sutapa : Sir Charles Gairdner Hospital
Palmer, Lyle : Mount Sinai Hospital
Zee, Phyllis : Northwestern University
Zhu, Xiaofeng : Case Western Reserve University
Content Type
Article
Published in
PLOS ONE
Funding Information
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
Publication Date
2012-11-14
Language
English
Record Created
2024-01-09