國家衛生研究院 NHRI:Item 3990099045/14070
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    題名: Upregulated heme biosynthesis increases obstructive sleep apnea severity: A pathway-based Mendelian randomization study
    作者: Wang, H;Kurniansyah, N;Cade, BE;Goodman, MO;Chen, H;Gottlieb, DJ;Gharib, SA;Purcell, SM;Lin, X;Saxena, R;Zhu, X;Durda, P;Tracy, R;Liu, Y;Taylor, KD;Johnson, WC;Gabriel, S;Smith, JD;Aguet, F;Ardlie, K;Blackwell, T;Reiner, AP;Rotter, JI;Rich, SS;Ayas, N;Burkardt, D;Cade, B;Chen, H;Clarkson-Townsend, D;Dutta, J;Ekunwe, L;Floyd, C;Gharib, S;Goodman, M;Gottlieb, D;Granot-Hershkovitz, E;Hale, L;Hanly, P;Heemann, S;Hsiung, C;Huang, T;Justice, A;Keenan, B;Lane, J;Liang, J;Lin, X;Liu, J;Lorincz-Comi, N;Magalang, U;Mazzotti, DR;Mei, H;Mikulla, J;Miller, A;Moafi-Madani, M;Ngo, D;O’Connell, J;Ochs-Balcom, H;Pack, A;Patel, S;Purcell, S;Redline, S;Saxena, R;Soemedi, R;Sofer, T;Sul, JH;Sunyaev, S;Tchio, C;Wang, H;Wilson, A;Xia, L;Zhang, M;Zhou, H;Zhu, X;Redline, S;Sofer, T;TOSTW Group
    貢獻者: Institute of Population Health Sciences
    摘要: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Iron and heme metabolism, implicated in ventilatory control and OSA comorbidities, was associated with OSA phenotypes in recent admixture mapping and gene enrichment analyses. However, its causal contribution was unclear. In this study, we performed pathway-level transcriptional Mendelian randomization (MR) analysis to investigate the causal relationships between iron and heme related pathways and OSA. In primary analysis, we examined the expression level of four iron/heme Reactome pathways as exposures and four OSA traits as outcomes using cross-tissue cis-eQTLs from the Genotype-Tissue Expression portal and published genome-wide summary statistics of OSA. We identify a significant putative causal association between up-regulated heme biosynthesis pathway with higher sleep time percentage of hypoxemia (p = 6.14 × 10–3). This association is supported by consistency of point estimates in one-sample MR in the Multi-Ethnic Study of Atherosclerosis using high coverage DNA and RNA sequencing data generated by the Trans-Omics for Precision Medicine project. Secondary analysis for 37 additional iron/heme Gene Ontology pathways did not reveal any significant causal associations. This study suggests a causal association between increased heme biosynthesis and OSA severity.
    日期: 2022-01-27
    關聯: Scientific Reports. 2022 Jan 27;12:Article number 1472.
    Link to: http://dx.doi.org/10.1038/s41598-022-05415-4
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-2322&DestApp=IC2JCR
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85123904808
    顯示於類別:[熊昭] 期刊論文

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