Association of genetic loci with sleep apnea in European Americans and African-Americans: the Candidate Gene Association Resource (CARe)

• Published in: PloS one Vol. 7; no. 11; p. e48836
• Main Authors: Patel, Sanjay R, Goodloe, Robert, De, Gourab, Kowgier, Matthew, Weng, Jia, Buxbaum, Sarah G, Cade, Brian, Fulop, Tibor, Gharib, Sina A, Gottlieb, Daniel J, Hillman, David, Larkin, Emma K, Lauderdale, Diane S, Li, Li, Mukherjee, Sutapa, Palmer, Lyle, Zee, Phyllis, Zhu, Xiaofeng, Redline, Susan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.11.2012; Public Library of Science (PLoS)
• Subjects: Adult; African Americans; African Americans - genetics; Aged; Alleles; Analysis; Apnea; Biology; Data processing; DNA microarrays; European Continental Ancestry Group - genetics; Family studies; Female; Gene loci; Genes; Genetic aspects; Genetic Association Studies; Genetic Loci; Genetic Predisposition to Disease; Genotype; Heart; Humans; Insomnia; Lungs; Lysophosphatidic acid; Male; Medicine; Middle Aged; Pathogenesis; Phenotype; Pleckstrin; Polymorphism, Single Nucleotide; Polysomnography; Prostaglandin E2; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Sleep; Sleep apnea; Sleep Apnea, Obstructive - genetics; Sleep disorders; Womens health; Canada; Mississippi; Perth Western Australia Australia; United States > US; Massachusetts; Illinois; Tennessee; Ohio; Chicago Illinois; Toronto Ontario Canada; Australia; Nashville Tennessee
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048836

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.