Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep
Autor: | Wendy S. Post, Jose S. Loredo, Shaun Purcell, Gregory J. Tranah, Craig L. Hanis, James G. Wilson, Matthew P. Conomos, Sonia Ancoli-Israel, Shamil R. Sunyaev, Sina A. Gharib, Katie L. Stone, Timothy A. Thornton, Kent D. Taylor, W. Craig Johnson, Phyllis C. Zee, Richard Barfield, Kathryn J. Reid, Adrienne M. Stilp, Raanan Arens, Han Chen, David J. Lederer, Sanjay R. Patel, Kenneth Rice, Kristine Yaffe, Tin Louie, Kevin J. Gleason, Daniel S. Evans, Alexis C. Frazier-Wood, Hao Mei, Jerome I. Rotter, Neomi Shah, Jiwon Lee, Richa Saxena, Xiaofeng Zhu, Lyle J. Palmer, Alberto R. Ramos, Cathy C. Laurie, Susan Redline, Brian E. Cade, Tamar Sofer, David R. Hillman, Heming Wang, Jianwen Cai, Xihong Lin, Daniel J. Gottlieb, Sutapa Mukherjee, Jennifer E. Below |
---|---|
Přispěvatelé: | Montgomery, Courtney G |
Rok vydání: | 2018 |
Předmět: |
Male
Cancer Research Neuronal Genome-wide association study Hypoxemia 0302 clinical medicine Polymorphism (computer science) Hexokinase 80 and over 2.1 Biological and endogenous factors Gene Regulatory Networks Aetiology Hypoxia Lung Genetics (clinical) Aged 80 and over 0303 health sciences Extracellular Matrix Proteins Serine Endopeptidases Sleep apnea Single Nucleotide Middle Aged Female medicine.symptom Sleep Research Interleukin-18 Receptor alpha Subunit Research Article Adult medicine.medical_specialty Adolescent Cell Adhesion Molecules Neuronal Quantitative Trait Loci Single-nucleotide polymorphism Nerve Tissue Proteins Biology Quantitative trait locus NLR Family Polymorphism Single Nucleotide 03 medical and health sciences Young Adult Sleep Apnea Syndromes Clinical Research Internal medicine Genetic variation NLR Family Pyrin Domain-Containing 3 Protein medicine Genetics Humans Polymorphism Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Aged Human Genome IL18R1 Computational Biology Genetic Variation medicine.disease Pyrin Domain-Containing 3 Protein Oxygen Reelin Protein Endocrinology Oxyhemoglobins Sleep Cell Adhesion Molecules 030217 neurology & neurosurgery Developmental Biology Genome-Wide Association Study |
Zdroj: | PLoS genetics, vol 15, iss 4 |
ISSN: | 1553-7404 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |