03102nas a2200565 4500008004100000022001400041245014200055210006900197260000900266300001100275490000600286520151100292653001001803653002201813653000901835653001201844653004001856653001101896653003201907653001701939653003801956653001301994653001102007653000902018653001602027653001402043653003602057653002002093653002902113100002102142700002002163700001502183700002102198700001402219700002202233700001602255700001702271700002002288700002402308700001902332700002002351700002502371700001102396700002202407700001702429700001702446700001802463700001902481856003602500 2012 eng d a1932-620300aAssociation of genetic loci with sleep apnea in European Americans and African-Americans: the Candidate Gene Association Resource (CARe).0 aAssociation of genetic loci with sleep apnea in European America c2012 ae488360 v73 a
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.
10aAdult10aAfrican Americans10aAged10aAlleles10aEuropean Continental Ancestry Group10aFemale10aGenetic Association Studies10aGenetic Loci10aGenetic Predisposition to Disease10aGenotype10aHumans10aMale10aMiddle Aged10aPhenotype10aPolymorphism, Single Nucleotide10aPolysomnography10aSleep Apnea, Obstructive1 aPatel, Sanjay, R1 aGoodloe, Robert1 aDe, Gourab1 aKowgier, Matthew1 aWeng, Jia1 aBuxbaum, Sarah, G1 aCade, Brian1 aFulop, Tibor1 aGharib, Sina, A1 aGottlieb, Daniel, J1 aHillman, David1 aLarkin, Emma, K1 aLauderdale, Diane, S1 aLi, Li1 aMukherjee, Sutapa1 aPalmer, Lyle1 aZee, Phyllis1 aZhu, Xiaofeng1 aRedline, Susan uhttps://chs-nhlbi.org/node/6178