@article{1ed4c70246464573832413f28d2dfa9f,
title = "Variants in angiopoietin-2 (ANGPT2) contribute to variation in nocturnal oxyhaemoglobin saturation level",
abstract = "Genetic determinants of sleep-disordered breathing (SDB), a common set of disorders that contribute to significant cardiovascular and neuropsychiatric morbidity, are not clear. Overnight nocturnal oxygen saturation (SaO2) is a clinically relevant and easily measured indicator of SDB severity but its genetic contribution has never been studied. Our recent study suggests nocturnal SaO2 is heritable. We performed linkage analysis, association analysis and haplotype analysis of average nocturnal oxyhaemoglobin saturation in participants in the Cleveland Family Study (CFS), followed by gene-based association and additional tests in four independent samples. Linkage analysis identified a peak (LOD=4.29) on chromosome 8p23. Follow-up association analysis identified two haplotypes in angiopoietin-2 (ANGPT2) that significantly contributed to the variation of SaO2 (P=8×10-5) and accounted for a portion of the linkage evidence. Gene-based association analysis replicated the association of ANGPT2 and nocturnal SaO2. A rare missense SNP rs200291021 in ANGPT2 was associated with serum angiopoietin-2 level (P=1.29×10-4), which was associated with SaO2 (P=0.002). Our study provides the first evidence for the association of ANGPT2, a gene previously implicated in acute lung injury syndromes, with nocturnal SaO2, suggesting that this gene has a broad range of effects on gas exchange, including influencing oxygenation during sleep.",
author = "Heming Wang and Cade, {B{\"a}rian E.} and Han Chen and Gleason, {Kevin J.} and Richa Saxena and Tao Feng and Larkin, {Emma K.} and Vasan, {Ramachandran S.} and Honghuang Lin and Patel, {Sanjay R.} and Tracy, {Russell P.} and Yongmei Liu and Gottlieb, {Daniel J.} and Below, {Jennifer E.} and Hanis, {Craig L.} and Petty, {Lauren E.} and Sunyaev, {Shamil R.} and Frazier-Wood, {Alexis C.} and Rotter, {Jerome I.} and Wendy Post and Xihong Lin and Susan Redline and Xiaofeng Zhu",
note = "Funding Information: The work was supported by the National Institutes of Health, the National Heart, Lung, Blood Institute grant HL113338, R01HL098433, HL46380, the National Human Genome Research Institute grant HG003054, and the Nation Science Foundation grant IIS-1218036. Provision of genotyping services is supported in part by NCATS CTSI grant UL1TR000124 and NIDDK DRC grant DK063491. The Atherosclerosis Risk in Communities (ARIC) Study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of North Carolina (N01-HC-55015, N01-HC-55018), Baylor College of Medicine (N01-HC-55016), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), and University of Mississippi Medical Center (N01-HC-55021). This manuscript was not prepared in collaboration with investigators of the ARIC Study and does not necessarily reflect the opinions or conclusions of the ARIC Study or the NHLBI. Multi-Ethnic Study of Atherosclerosis (MESA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and CTSA UL1-RR-024156. The MESA epigenomes study is supported by 1R01HL101250. Starr County Health Studies (Starr) is supported in part by grants R01 DK073541, U01 DK085501, R01 AI085014, and R01 HL102830 from the National Institutes of Health, and funds from the University of Texas Health Science Center at Houston. The work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195 and HHSN268201500001I) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. Publisher Copyright: {\textcopyright} The Author 2016. Published by Oxford University Press. All rights reserved.",
year = "2016",
doi = "10.1093/hmg/ddw324",
language = "English (US)",
volume = "25",
pages = "5244--5253",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "23",
}