title: Association of genetic loci with sleep apnea in European Americans and African-Americans: the Candidate Gene Association Resource (CARe).
abstract: 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.
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America. spatel@partners.org
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
authors.forename: Robert
authors.initials: R
authors.lastname: Goodloe
authors.forename: Gourab
authors.initials: G
authors.lastname: De
authors.forename: Matthew
authors.initials: M
authors.lastname: Kowgier
authors.forename: Jia
authors.initials: J
authors.lastname: Weng
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.forename: Brian
authors.initials: B
authors.lastname: Cade
authors.forename: Tibor
authors.initials: T
authors.lastname: Fulop
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Gottlieb
authors.forename: David
authors.initials: D
authors.lastname: Hillman
authors.forename: Emma K
authors.initials: EK
authors.lastname: Larkin
authors.forename: Diane S
authors.initials: DS
authors.lastname: Lauderdale
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Sutapa
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Lyle
authors.initials: L
authors.lastname: Palmer
authors.forename: Phyllis
authors.initials: P
authors.lastname: Zee
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017286:Polysomnography; D020181:Sleep Apnea, Obstructive / Q000235:genetics*; D044465:White People / Q000235:genetics*