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Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.
Wednesday,2019-05-22 16:34 America/Los_Angeles — ecterry
| Title | Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Cade, BE, Chen, H, Stilp, AM, Louie, T, Ancoli-Israel, S, Arens, R, Barfield, R, Below, JE, Cai, J, Conomos, MP, Evans, DS, Frazier-Wood, AC, Gharib, SA, Gleason, KJ, Gottlieb, DJ, Hillman, DR, W Johnson, C, Lederer, DJ, Lee, J, Loredo, JS, Mei, H, Mukherjee, S, Patel, SR, Post, WS, Purcell, SM, Ramos, AR, Reid, KJ, Rice, K, Shah, NA, Sofer, T, Taylor, KD, Thornton, TA, Wang, H, Yaffe, K, Zee, PC, Hanis, CL, Palmer, LJ, Rotter, JI, Stone, KL, Tranah, GJ, Wilson, JG, Sunyaev, SR, Laurie, CC, Zhu, X, Saxena, R, Lin, X, Redline, S |
| Journal | PLoS Genet |
| Volume | 15 |
| Issue | 4 |
| Pagination | e1007739 |
| Date Published | 2019 04 |
| ISSN | 1553-7404 |
| Keywords | Adolescent, Adult, Aged, Aged, 80 and over, Cell Adhesion Molecules, Neuronal, Computational Biology, Extracellular Matrix Proteins, Female, Gene Regulatory Networks, Genetic Variation, Genome-Wide Association Study, Hexokinase, Humans, Hypoxia, Interleukin-18 Receptor alpha Subunit, Male, Middle Aged, Nerve Tissue Proteins, NLR Family, Pyrin Domain-Containing 3 Protein, Oxygen, Oxyhemoglobins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Serine Endopeptidases, Sleep, Sleep Apnea Syndromes, Young Adult |
| Abstract | <p>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.</p> |
| DOI | 10.1371/journal.pgen.1007739 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 30990817 |
| PubMed Central ID | PMC6467367 |
| Grant List | HHSN268201300049C / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States HHSN268201300046C / HL / NHLBI NIH HHS / United States U01 AG042145 / AG / NIA NIH HHS / United States RC2 AR058973 / AR / NIAMS NIH HHS / United States HHSN268201300005C / HL / NHLBI NIH HHS / United States U01 DK085501 / DK / NIDDK NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States U01 AG042140 / AG / NIA NIH HHS / United States U01 AG042124 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL070847 / HL / NHLBI NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States R01 AI085014 / AI / NIAID NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States U54 GM115428 / GM / NIGMS NIH HHS / United States HHSN268201300047C / HL / NHLBI NIH HHS / United States UL1 TR000128 / TR / NCATS NIH HHS / United States UL1 TR001420 / TR / NCATS NIH HHS / United States U01 AG042139 / AG / NIA NIH HHS / United States R21 HL140437 / HL / NHLBI NIH HHS / United States R01 HL070841 / HL / NHLBI NIH HHS / United States U01 AG042143 / AG / NIA NIH HHS / United States R01 DK073541 / DK / NIDDK NIH HHS / United States R01 HL070838 / HL / NHLBI NIH HHS / United States R01 HL070842 / HL / NHLBI NIH HHS / United States HHSN268201300048C / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01 AG027810 / AG / NIA NIH HHS / United States R01 HL070839 / HL / NHLBI NIH HHS / United States U01 AR066160 / AR / NIAMS NIH HHS / United States UL1 TR001079 / TR / NCATS NIH HHS / United States R01 HL071194 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States R01 HL070837 / HL / NHLBI NIH HHS / United States R01 HL070848 / HL / NHLBI NIH HHS / United States U01 AG042168 / AG / NIA NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States R21 AG056952 / AG / NIA NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States HHSN268201300050C / HL / NHLBI NIH HHS / United States R01 HL102830 / HL / NHLBI NIH HHS / United States R01 AR051124 / AR / NIAMS NIH HHS / United States |
ePub date:
19/04