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
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