- Record: found
- Abstract: found
- Article: found
Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep
research-article
Author(s):
Brian E. Cade
1
,
2
,
3
,
* ,
Han Chen
4
,
5 ,
Adrienne M. Stilp
6 ,
Tin Louie
6 ,
Sonia Ancoli-Israel
7 ,
Raanan Arens
8 ,
Richard Barfield
9 ,
Jennifer E. Below
10 ,
Jianwen Cai
11 ,
Matthew P. Conomos
6 ,
Daniel S. Evans
12 ,
Alexis C. Frazier-Wood
13 ,
Sina A. Gharib
14 ,
Kevin J. Gleason
1
,
15 ,
Daniel J. Gottlieb
1
,
2
,
16 ,
David R. Hillman
17 ,
W. Craig Johnson
6 ,
David J. Lederer
18 ,
Jiwon Lee
1 ,
Jose S. Loredo
19 ,
Hao Mei
20 ,
Sutapa Mukherjee
21
,
22 ,
Sanjay R. Patel
23 ,
Wendy S. Post
24 ,
Shaun M. Purcell
1
,
2
,
3 ,
Alberto R. Ramos
25 ,
Kathryn J. Reid
26 ,
Ken Rice
6 ,
Neomi A. Shah
27 ,
Tamar Sofer
1
,
2
,
6 ,
Kent D. Taylor
28 ,
Timothy A. Thornton
6 ,
Heming Wang
1
,
2
,
3 ,
Kristine Yaffe
29
,
30 ,
Phyllis C. Zee
26 ,
Craig L. Hanis
4 ,
Lyle J. Palmer
31 ,
Jerome I. Rotter
28 ,
Katie L. Stone
12 ,
Gregory J. Tranah
12 ,
James G. Wilson
32 ,
Shamil R. Sunyaev
3
,
33
,
34 ,
Cathy C. Laurie
6 ,
Xiaofeng Zhu
35 ,
Richa Saxena
1
,
2
,
3
,
36 ,
Xihong Lin
9 ,
Susan Redline
1
,
2
,
37
Publication date (Electronic):
16 April 2019
Journal:
PLoS Genetics
Publisher:
Public Library of Science
Read this article at
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Abstract
Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10 −6 were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO 2 (rs78136548 p = 2.70 × 10 −10). SNPs at 10q22 were associated with all three traits including average SpO 2 (rs72805692 p = 4.58 × 10 −8). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.
Author summary
Variation in oxyhemoglobin saturation, the proportion of oxygen-saturated to total hemoglobin in the blood, is associated with numerous disorders and is a predictor of health outcomes including mortality, incident heart failure, and dementia. Despite the fundamental role of oxygen saturation in normal and abnormal physiology, there are few large-scale genetic studies of oxygen saturation performed across populations. Overnight measurements provide more variability than daytime levels due to the “stresses” associated with normal and disordered breathing, and also provide an important measure of sleep apnea severity, a common disorder in the population that is associated with considerable morbidity. In this study, for the first time, we identified multiple replicated genome-significant associations based on up to 22,736 individuals from 10 cohort studies. Our findings suggest a contribution of inflammatory genes such as the Interleukin 18 receptor subunit genes to the genetic architecture of sleep-disordered breathing. These results extend our understanding of the genetics of oxyhemoglobin saturation and sleep-disordered breathing and may provide further insight into the biology of associated diseases.
Related collections
Most cited references82
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- Abstract: found
- Article: not found
Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages.
Macrophages activated by the TLR4 agonist LPS undergo dramatic changes in their metabolic activity. We here show that LPS induces expression of the key metabolic regulator Pyruvate Kinase M2 (PKM2). Activation of PKM2 using two well-characterized small molecules, DASA-58 and TEPP-46, inhibited LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes. Activation of PKM2 attenuated an LPS-induced proinflammatory M1 macrophage phenotype while promoting traits typical of an M2 macrophage. We show that LPS-induced PKM2 enters into a complex with Hif-1α, which can directly bind to the IL-1β promoter, an event that is inhibited by activation of PKM2. Both compounds inhibited LPS-induced glycolytic reprogramming and succinate production. Finally, activation of PKM2 by TEPP-46 in vivo inhibited LPS and Salmonella typhimurium-induced IL-1β production, while boosting production of IL-10. PKM2 is therefore a critical determinant of macrophage activation by LPS, promoting the inflammatory response.
- Record: found
- Abstract: found
- Article: found
Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics
Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease genes are enriched among significant associations for related traits, suggesting that smaller alterations of these genes may cause a spectrum of milder phenotypes.
- Record: found
- Abstract: found
- Article: not found
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Sarah E. Corcoran, Luke A.J O’Neill (2016)
HIF1α is a common component of pathways involved in the control of cellular metabolism and has a role in regulating immune cell effector functions. Additionally, HIF1α is critical for the maturation of dendritic cells and for the activation of T cells. HIF1α is induced in LPS-activated macrophages, where it is critically involved in glycolysis and the induction of proinflammatory genes, notably Il1b. The mechanism of LPS-stimulated HIF1α induction involves succinate, which inhibits prolyl hydroxylases (PHDs). Pyruvate kinase M2 (PKM2) is also induced and interacts with and promotes the function of HIF1α. In another critical inflammatory cell type, Th17 cells, HIF1α acts via the retinoic acid-related orphan receptor-γt (RORγt) to drive Th17 differentiation. HIF1α is therefore a key reprogrammer of metabolism in inflammatory cells that promotes inflammatory gene expression.
Author and article information
Contributors
Brian E. Cade:
ORCID: http://orcid.org/0000-0003-1424-0673
Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole:
SoftwareRole: VisualizationRole: Writing – original draftRole: Writing – review &
editing
Han Chen:
ORCID: http://orcid.org/0000-0002-9510-4923
Role: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing
– review & editing
Adrienne M. Stilp: Role: Data curationRole: Formal analysisRole: Writing – review & editing
Tin Louie: Role: Data curationRole: Formal analysisRole: Writing – review & editing
Sonia Ancoli-Israel: Role: ConceptualizationRole: Writing – review & editing
Raanan Arens: Role: ConceptualizationRole: Writing – review & editing
Richard Barfield:
ORCID: http://orcid.org/0000-0002-6276-7704
Role: Data curationRole: Writing – review & editing
Jennifer E. Below: Role: Data curationRole: Writing – review & editing
Jianwen Cai: Role: ConceptualizationRole: ResourcesRole: Writing – review & editing
Matthew P. Conomos: Role: Data curationRole: Writing – review & editing
Daniel S. Evans: Role: Data curationRole: Writing – review & editing
Alexis C. Frazier-Wood: Role: Data curationRole: Writing – review & editing
Sina A. Gharib: Role: Data curationRole: Writing – review & editing
Kevin J. Gleason: Role: Data curationRole: Writing – review & editing
Daniel J. Gottlieb:
ORCID: http://orcid.org/0000-0001-8812-8751
Role: ConceptualizationRole: Writing – review & editing
David R. Hillman: Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
W. Craig Johnson: Role: Data curationRole: Writing – review & editing
David J. Lederer:
ORCID: http://orcid.org/0000-0001-5258-0228
Role: Data curationRole: Writing – review & editing
Jiwon Lee:
ORCID: http://orcid.org/0000-0002-4079-7494
Role: Data curationRole: Writing – review & editing
Jose S. Loredo: Role: ConceptualizationRole: Writing – review & editing
Hao Mei: Role: Data curationRole: Writing – review & editing
Sutapa Mukherjee:
ORCID: http://orcid.org/0000-0001-5021-1648
Role: Data curationRole: ResourcesRole: Writing – review & editing
Sanjay R. Patel:
ORCID: http://orcid.org/0000-0002-9142-5172
Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
Wendy S. Post: Role: Data curationRole: Writing – review & editing
Shaun M. Purcell: Role: Data curationRole: Writing – review & editing
Alberto R. Ramos: Role: Data curationRole: Writing – review & editing
Kathryn J. Reid: Role: Data curationRole: Writing – review & editing
Ken Rice: Role: Data curationRole: Writing – review & editing
Neomi A. Shah: Role: Data curationRole: Writing – review & editing
Tamar Sofer:
ORCID: http://orcid.org/0000-0001-8520-8860
Role: Data curationRole: Writing – review & editing
Kent D. Taylor: Role: Data curationRole: Writing – review & editing
Timothy A. Thornton: Role: Data curationRole: Writing – review & editing
Heming Wang: Role: Data curationRole: Writing – review & editing
Kristine Yaffe: Role: Data curationRole: Writing – review & editing
Phyllis C. Zee: Role: Data curationRole: Writing – review & editing
Craig L. Hanis:
ORCID: http://orcid.org/0000-0002-4880-5348
Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Writing – review
& editing
Lyle J. Palmer:
ORCID: http://orcid.org/0000-0002-1628-3055
Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Writing – review
& editing
Jerome I. Rotter:
ORCID: http://orcid.org/0000-0001-7191-1723
Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Writing – review
& editing
Katie L. Stone: Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Writing – review
& editing
Gregory J. Tranah: Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Writing – review
& editing
James G. Wilson: Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Writing – review
& editing
Shamil R. Sunyaev: Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
Cathy C. Laurie:
ORCID: http://orcid.org/0000-0003-2572-4040
Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review &
editing
Xiaofeng Zhu: Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Writing – original
draftRole: Writing – review & editing
Richa Saxena: Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Writing – original
draftRole: Writing – review & editing
Xihong Lin: Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole:
Writing – review & editing
Susan Redline: Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole:
Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole:
Writing – review & editing
Courtney G. Montgomery: Role: Editor
Journal
Journal ID (nlm-ta): PLoS Genet
Journal ID (iso-abbrev): PLoS Genet
Journal ID (publisher-id): plos
Journal ID (pmc): plosgen
Title:
PLoS Genetics
Publisher:
Public Library of Science
(San Francisco, CA USA
)
ISSN
(Print):
1553-7390
ISSN
(Electronic):
1553-7404
Publication date
(Electronic):
16
April
2019
Publication date Collection:
April
2019
Volume: 15
Issue: 4
Electronic Location Identifier: e1007739
Affiliations
[1
]
Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA,
United States of America
[3
]
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, United
States of America
[4
]
Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental
Sciences, School of Public Health, The University of Texas Health Science Center at
Houston, Houston, TX United States of America
[5
]
Center for Precision Health, School of Public Health and School of Biomedical Informatics,
The University of Texas Health Science Center at Houston, Houston, TX United States
of America
[8
]
The Children’s Hospital at Montefiore, Division of Respiratory and Sleep Medicine,
Albert Einstein College of Medicine, Bronx, NY, United States of America
[9
]
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA,
United States of America
[10
]
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN,
United States of America
[11
]
Department of Biostatistics, Gillings School of Global Public Health, University of
North Carolina, Chapel Hill, NC, United States of America
[12
]
California Pacific Medical Center Research Institute, San Francisco, CA, United States
of America
[13
]
USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston,
TX, United States of America
[14
]
Computational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Division
of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle
WA, United States of America
[15
]
Department of Public Health Sciences, University of Chicago, Chicago, IL, United States
of America
[17
]
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital,
Perth, Western Australia, Australia
[18
]
Departments of Medicine and Epidemiology, Columbia University, New York, NY, United
States of America
[19
]
Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, UC
San Diego School of Medicine, La Jolla, CA, United States of America
[20
]
Department of Data Science, University of Mississippi Medical Center, Jackson, MS,
United States of America
[21
]
Sleep Health Service, Respiratory and Sleep Services, Southern Adelaide Local Health
Network, Adelaide, South Australia
[23
]
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh,
Pittsburgh, PA, United States of America
[25
]
Department of Neurology, University of Miami Miller School of Medicine, Miami, FL,
United States of America
[26
]
Department of Neurology, Center for Circadian and Sleep Medicine, Northwestern University
Feinberg School of Medicine, Chicago, IL, United States of America
[27
]
Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine
at Mount Sinai, New York, NY, United States of America
[28
]
The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics
and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, United States
of America
[29
]
Department of Psychiatry, Neurology, and Epidemiology and Biostatistics, University
of California at San Francisco, San Francisco, CA, United States of America
[32
]
Department of Physiology and Biophysics, University of Mississippi Medical Center,
Jackson MS, United States of America
[35
]
Department of Population and Quantitative Health Sciences, Case Western Reserve University,
Cleveland, OH, United States of America
[36
]
Center for Genomic Medicine and Department of Anesthesia, Pain, and Critical Care
Medicine, Massachusetts General Hospital, Boston, MA, United States of America
Author notes
Author information
Brian E. Cade
http://orcid.org/0000-0003-1424-0673
Han Chen
http://orcid.org/0000-0002-9510-4923
Richard Barfield
http://orcid.org/0000-0002-6276-7704
Daniel J. Gottlieb
http://orcid.org/0000-0001-8812-8751
David J. Lederer
http://orcid.org/0000-0001-5258-0228
Jiwon Lee
http://orcid.org/0000-0002-4079-7494
Sutapa Mukherjee
http://orcid.org/0000-0001-5021-1648
Sanjay R. Patel
http://orcid.org/0000-0002-9142-5172
Tamar Sofer
http://orcid.org/0000-0001-8520-8860
Craig L. Hanis
http://orcid.org/0000-0002-4880-5348
Lyle J. Palmer
http://orcid.org/0000-0002-1628-3055
Jerome I. Rotter
http://orcid.org/0000-0001-7191-1723
Cathy C. Laurie
http://orcid.org/0000-0003-2572-4040
Article
Publisher ID: PGENETICS-D-18-00785DOI: 10.1371/journal.pgen.1007739
PMC ID: 6467367
PubMed ID: 30990817
SO-VID: 94aebbd3-6739-4a82-ade5-12e12d017218
License:
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
History
Date
received
: 17
April
2018
Date
accepted
: 3
October
2018
Page count
Figures: 2,
Tables: 3,
Pages: 31
Funding
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: K01-HL135405-01
Award Recipient
:
ORCID: http://orcid.org/0000-0003-1424-0673
Brian E. Cade
Funded by: funder-id http://dx.doi.org/10.13039/100001465, American Thoracic Society;
Award Recipient
:
ORCID: http://orcid.org/0000-0003-1424-0673
Brian E. Cade
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01-HL113338-04
Award Recipient
:
Susan Redline
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R35-HL135818-01
Award Recipient
:
Susan Redline
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: 5-R01-HL046380-15
Award Recipient
:
Susan Redline
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: 5-KL2-RR024990-05
Award Recipient
:
Susan Redline
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01-HC-55015
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
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Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95160
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95161
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95162
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95163
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95164
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95165
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95166
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95167
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95168
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: N01HC95169
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: UL1TR000040
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: UL1TR001079
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: UL1TR001420
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: UL1TR001881
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL56984
Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
Award ID: UL1TR000124
Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
Award ID: U01AG027810
Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
Award ID: U01AG042124
Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
Award ID: U01AG042139
Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
Award ID: U01AG042140
Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
Award ID: U01AG042143
Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
Award ID: U01AG042145
Funded by: funder-id http://dx.doi.org/10.13039/100000049, National Institute on Aging;
Award ID: U01AG042168
Funded by: funder-id http://dx.doi.org/10.13039/100000069, National Institute of Arthritis and Musculoskeletal and Skin Diseases;
Award ID: U01AR066160
Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
Award ID: UL1TR000128
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL071194
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL070848
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL070847
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL070842
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL070841
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL070837
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL070838
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL070839
Funded by: funder-id http://dx.doi.org/10.13039/100000069, National Institute of Arthritis and Musculoskeletal and Skin Diseases;
Award ID: R01AR051124
Funded by: funder-id http://dx.doi.org/10.13039/100000069, National Institute of Arthritis and Musculoskeletal and Skin Diseases;
Award ID: RC2AR058973
Funded by: funder-id http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
Award ID: R01DK073541
Funded by: funder-id http://dx.doi.org/10.13039/100000062, National Institute of Diabetes and Digestive and Kidney Diseases;
Award ID: U01DK085501
Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
Award ID: R01AI085014
Funded by: funder-id http://dx.doi.org/10.13039/100000050, National Heart, Lung, and Blood Institute;
Award ID: R01HL102830
Funded by: University of Texas Health Science Center at Houston
Funded by: Sir Charles Gairdner Research Foundation
Funded by: funder-id http://dx.doi.org/10.13039/100008188, Hollywood Private Hospital Research Foundation;
Funded by: Western Australian Sleep Disorders Research Institute
Funded by: Centre for Genetic Epidemiology and Biostatistics at the University of Western Australia
Funded by: funder-id http://dx.doi.org/10.13039/100012118, Ontario Institute for Cancer Research;
Funded by: McLaughlin Centre Accelerator Grant from the University of Toronto
Brian Cade is supported by grants from the National Institutes of Health [K01-HL135405-01,
R01-HL113338-04, R35-HL135818-01] and the American Thoracic Society Foundation (
http://foundation.thoracic.org). The Sleep Reading Center of Brigham and Women's Hospital has been supported by
National Institutes of Health grants [5-R01-HL046380-15 and 5-KL2-RR024990-05]. 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 Cardiovascular Health
Study (CHS) research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C,
N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086;
and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393,
and R01HL130114 with additional contribution from the National Institute of Neurological
Disorders and Stroke (NINDS). Genotyping among the African-American cohort was supported
in part by HL085251Additional support was provided through R01AG023629 from the National
Institute on Aging (NIA). A full list of principal CHS investigators and institutions
can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part
by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124,
and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research
Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research
Center. The Framingham Heart Study is conducted and supported by NHLBI in collaboration
with Boston University (Contract No. N01-HC-25195). Funding for SHARe Affymetrix genotyping
was provided by NHLBI Contract N02-HL- 64278. SHARe Illumina genotyping was provided
under an agreement between Illumina and Boston University. Funding support for the
Framingham Sleep Heart Health Study was provided by NIH/NHLBI grant U01 HL 53941.
The Hispanic Community Health Study/Study of Latinos is a collaborative study supported
by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University
of North Carolina (HHSN268201300001I / N01-HC-65233), University of Miami (HHSN268201300004I
/ N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I / N01-HC-65235),
University of Illinois at Chicago – HHSN268201300003I / N01-HC-65236 Northwestern
Univ), and San Diego State University (HHSN268201300005I / N01-HC-65237). The following
Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of
funds to the NHLBI: National Institute on Minority Health and Health Disparities,
National Institute on Deafness and Other Communication Disorders, National Institute
of Dental and Craniofacial Research, National Institute of Diabetes and Digestive
and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH
Institution-Office of Dietary Supplements. The Genetic Analysis Center at Washington
University was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and
MOD03). The Jackson Heart Study is supported and conducted in collaboration with Jackson
State University (HHSN268201300049C and HHSN268201300050C), Tougaloo College (HHSN268201300048C),
and the University of Mississippi Medical Center (HHSN268201300046C and HHSN268201300047C)
contracts from the National Heart, Lung, and Blood Institute (NHLBI) and the National
Institute for Minority Health and Health Disparities (NIMHD). Dr. Wilson is supported
by U54GM115428 from the National Institute of General Medical Sciences. The authors
thank the participants and data collection staff of the Jackson Heart Study. The views
expressed in this manuscript are those of the authors and do not necessarily represent
the views of the National Heart, Lung, and Blood Institute; the National Institutes
of Health; or the U.S. Department of Health and Human Services. The Multi-Ethnic Study
of Atherosclerosis (MESA) is conducted and supported by the NHLBI in collaboration
with MESA investigators. MESA and the MESA SHARe project are conducted and supported
by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA
investigators. Support for MESA is provided by contracts HHSN268201500003I, 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, UL1-TR-000040, UL1-TR-001079,
UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided
by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara,
California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts,
USA) using the Affymetrix Genome-Wide Human SNP Array 6.0. Funding support for the
Sleep Polysomnography dataset was provided by grant HL56984. Provision of genotyping
services supported in part by NCATS CTSI grant UL1TR000124 and NIDDK DRC grant DK063491.
The Osteoporotic Fractures in Men (MrOS) Study is supported by NIH funding. The following
institutes provide support: the National Institute on Aging (NIA), the National Institute
of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NCATS, and NIH Roadmap
for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124,
U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160,
and UL1 TR000128. The NHLBI provides funding for the MrOS Sleep ancillary study "Outcomes
of Sleep Disorders in Older Men" under the following grant numbers: R01 HL071194,
R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838,
and R01 HL070839. The NIAMS provides funding for the MrOS ancillary study ‘Replication
of candidate gene associations and bone strength phenotype in MrOS’ under the grant
number R01 AR051124. The NIAMS provides funding for the MrOS ancillary study ‘GWAS
in MrOS and SOF’ under the grant number RC2 AR058973. The Starr County Health Studies
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. Funding for the Western Australian Sleep Health Study was
obtained from the Sir Charles Gairdner and Hollywood Private Hospital Research Foundations,
the Western Australian Sleep Disorders Research Institute, and the Centre for Genetic
Epidemiology and Biostatistics at the University of Western Australia. Funding for
the GWAS genotyping obtained from the Ontario Institute for Cancer Research and a
McLaughlin Centre Accelerator Grant from the University of Toronto. The funders had
no role in study design, data collection and analysis, decision to publish, or preparation
of the manuscript.
Categories
Subject:
Research Article
Custom metadata
Data Availability Full meta-analysis results are freely available from
http://www.sleepdisordergenetics.org/informational/data
ScienceOpen disciplines: Genetics
Data availability:
ScienceOpen disciplines: Genetics