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Record W2937441727 · doi:10.1371/journal.pgen.1007739

Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep

2019· review· en· W2937441727 on OpenAlexfundno aff
Brian E. Cade, Han Chen, Adrienne M. Stilp, Tin Louie, Sonia Ancoli‐Israel, Raanan Arens, Richard Barfield, Jennifer E. Below, Jianwen Cai, Matthew P. Conomos, Daniel S. Evans, Alexis C. Wood, Sina A. Gharib, Kevin J. Gleason, Daniel J. Gottlieb, David R. Hillman, W. Craig Johnson, David J. Lederer, Jiwon Lee, José S. Loredo, Hao Mei, Sutapa Mukherjee, Sanjay R. Patel, Wendy S. Post, Shaun Purcell, Alberto R. Ramos, Kathryn J. Reid, Kenneth Rice, Neomi Shah, Tamar Sofer, Kent D. Taylor, Timothy A. Thornton, Heming Wang, Kristine Yaffe, Phyllis C. Zee, Craig L. Hanis, Lyle J. Palmer, Jerome I. Rotter, Katie L. Stone, Gregory J. Tranah, James G. Wilson, Shamil Sunyaev, Cathy C. Laurie, Xiaofeng Zhu, Richa Saxena, Xihong Lin, Susan Redline

Bibliographic record

VenuePLoS Genetics · 2019
Typereview
Languageen
FieldMedicine
TopicErythrocyte Function and Pathophysiology
Canadian institutionsnot available
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute on Minority Health and Health DisparitiesNational Center for Advancing Translational SciencesNational Institute of Dental and Craniofacial ResearchNational Institute of Environmental Health SciencesNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesNational Institute on AgingUniversity of Illinois at Urbana-ChampaignAmerican Thoracic SocietyBroad InstituteNational Center for Research ResourcesNational Institute of Allergy and Infectious DiseasesUniversity of Texas Health Science Center at HoustonNational Human Genome Research InstituteBrigham and Women's HospitalOntario Institute for Cancer ResearchUniversity of TorontoHollywood Private Hospital Research FoundationNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Diabetes and Digestive and Kidney DiseasesJackson State UniversityJohns Hopkins UniversityNational Heart, Lung, and Blood InstituteUniversity of MiamiNorthwestern UniversityUniversity of MinnesotaSan Diego State UniversityNational Institutes of HealthOffice of Dietary SupplementsU.S. Department of Health and Human Services
KeywordsBiologyHexokinaseGeneticsEndocrinologyGlycolysisMetabolism

Abstract

fetched live from OpenAlex

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 SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.005
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.086
GPT teacher head0.313
Teacher spread0.227 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations42
Published2019
Admission routes1
Has abstractyes

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