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5. Neutrophil-to-lymphocyte ratio and all-cause mortality with and without myeloproliferative neoplasms—a Danish longitudinal study

Author

Larsen, Morten Kranker, Skov, Vibe, Kjær, Lasse, Eickhardt-Dalbøge, Christina Schjellerup, Knudsen, Trine Alma, Kristiansen, Marie Hvelplund, Sørensen, Anders Lindholm, Wienecke, Troels, Andersen, Morten, Ottesen, Johnny T., Gudmand-Høyer, Johanne, Snyder, Jordan Andrew, Andersen, Mikkel Porsborg, Torp-Pedersen, Christian, Poulsen, Henrik Enghusen, Stiehl, Thomas, Hasselbalch, Hans Carl, and Ellervik, Christina

Published
2024
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6. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

Sterenborg, Rosalie B. T. M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A. L. M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C. M., Linneberg, Allan, Lominchar, Jesus V. T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N. A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I. A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H. R., Wouters, Hanneke J. C. M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W. A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, and Medici, Marco

Published
2024
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9. Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

Author

Young, William J., Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R., Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R., Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L., Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L., Sitlani, Colleen M., Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A., Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Jackson, Rebecca D., Kors, Jan A., Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W., Morrison, Alanna C., Navarro, Pau, Porteous, David J., Pramstaller, Peter P., Reiner, Alexander P., Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z., Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R., Whitsel, Eric A., Wiggins, Kerri L., Arking, Dan E., Avery, Christy L., Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J.Wouter, Mook-Kanamori, Dennis O., Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M., Pattaro, Cristian, Ribeiro, Antonio Luiz P., Rotter, Jerome I., Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James G., Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J., Wilson, James F., Kanters, Jørgen K., Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D., Tereshchenko, Larisa G., and Munroe, Patricia B.

Published
2023
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13. The gut microbiota in patients with polycythemia vera is distinct from that of healthy controls and varies by treatment

Author

Eickhardt-Dalbøge, Christina Schjellerup, Ingham, Anna Cäcilia, Andersen, Lee O'Brien, Nielsen, Henrik V., Fuursted, Kurt, Stensvold, Christen Rune, Larsen, Morten Kranker, Kjær, Lasse, Christensen, Sarah Friis, Knudsen, Trine Alma, Skov, Vibe, Ellervik, Christina, Olsen, Lars Rønn, Hasselbalch, Hans Carl, Nielsen, Xiaohui Chen, and Christensen, Jens Jørgen Elmer

Published
2023
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17. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author

Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki V., Hutri-Kähönen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O’Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome I., Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.

Published
2022
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18. Genomic profiling of a randomized trial of interferon-α vs hydroxyurea in MPN reveals mutation-specific responses

Author

Knudsen, Trine Alma, Skov, Vibe, Stevenson, Kristen, Werner, Lillian, Duke, William, Laurore, Charles, Gibson, Christopher J., Nag, Anwesha, Thorner, Aaron R., Wollison, Bruce, Hansen, Dennis Lund, Ellervik, Christina, El Fassi, Daniel, de Stricker, Karin, Ocias, Lukas Frans, Brabrand, Mette, Bjerrum, Ole Weis, Overgaard, Ulrik Malthe, Frederiksen, Mikael, Kristensen, Thomas Kielsgaard, Kruse, Torben A., Thomassen, Mads, Mourits-Andersen, Torben, Severinsen, Marianne Tang, Stentoft, Jesper, Starklint, Joern, Neuberg, Donna S., Kjaer, Lasse, Larsen, Thomas Stauffer, Hasselbalch, Hans Carl, Lindsley, R. Coleman, and Mullally, Ann

Published
2022
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19. Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study.

Author

Ellervik, Christina, Boulakh, Lena, Teumer, Alexander, Marouli, Eirini, Kuś, Aleksander, Buch Hesgaard, Helena, Heegaard, Steffen, Blankers, Lizette, Sterenborg, Rosalie, Åsvold, Bjørn Olav, Winkler, Thomas Wolfgang, Medici, Marco, and Kjaergaard, Alisa Devedzic

Abstract

Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10−4), cataract (p = 3 × 10−3), and T1D (p = 1 × 10−3), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10−4). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10−3). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Thyroid dysfunction and exudative age‐related macular degeneration – A longitudinal nationwide registry‐based cohort study.

Author

Boulakh, Lena, Isaksen, Jonas L., Poulsen, Henrik Enghusen, Faber, Jens, Heegaard, Steffen, Nygaard, Birte, Kanters, Jørgen Kim, Toft, Peter Bjerre, Mortens Udholm, Patricia, Bek, Toke, Buch Hesgaard, Helena, and Ellervik, Christina

Subjects
THYROID diseases, MACULAR degeneration, HYPERTHYROIDISM, HYPOTHYROIDISM, THYROID hormones
Abstract

Purpose: The association between thyroid dysfunction and exudative age‐related macular degeneration (AMD) is unknown. Methods: In this Danish longitudinal nationwide registry‐based cohort study we included all Danish residents aged 50–100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti‐thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti‐VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group. Results: We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow‐up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10–1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13–1.34; p < 0.001) were both associated with the development of exudative AMD. The age‐stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population. Conclusion: This is the first longitudinal nationwide study showing that both hypo‐ and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association. [ABSTRACT FROM AUTHOR]

Published
2024
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21. The CHIP-clinic as the catalyst of preventive medicine.

Author

Hasselbalch, Hans Carl, Skov, Vibe, Kjaer, Lasse, Knudsen, Trine Alma, Eickhardt-Dalbøge, Christina Schjellerup, Ellervik, Christina, Cordua, Sabrina, Sørensen, Anders Lindholm, Christensen, Sarah Friis, Kristiansen, Marie Hvelplund, Lindholt, Jes Sanddal, Thomassen, Mads, Kruse, Torben A., Bruun, Niels Eske, Lindholm, Matias Greve, Nielsen, Claus Henrik, Egyed, Miklos, März, Winfried, Larsen, Morten Kranker, and Wienecke, Troels

Published
2024
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22. The CALR mutations enhance the expression of the immunosuppressive proteins GARP and LAP on peripheral blood lymphocytes through increased binding of activated platelets.

Author

Holmström, Morten Orebo, Ruders, Josephine Hallundbæk, Riley, Caroline Hasselbalch, Larsen, Morten Kranker, Grauslund, Jacob Handlos, Kjær, Lasse, Skov, Vibe, Ellervik, Christina, Guo, Belinda B., Linden, Matthew, Hasselbalch, Hans Carl, and Andersen, Mads Hald

Subjects
TRANSFORMING growth factors-beta, GENE expression, PLATELET count, MYELOPROLIFERATIVE neoplasms, PEPTIDES
Abstract

Summary: Recently, an antibody which inhibits the glycoprotein A repetitions predominant (GARP)‐mediated release of active transforming growth factor beta (TGFβ) from the TGFβ propeptide latency‐associated peptide (LAP) showed preclinical activity in a murine model of the chronic myeloproliferative neoplasms (MPN). Consequently, we investigated the expression of the immunosuppressive molecules LAP and GARP on peripheral blood lymphocytes from 56 MPN patients and 11 healthy donors (HD). We found that lymphocytes from patients with MPN express higher levels of LAP and GARP with no strong differences found between the different MPN diagnoses. The impact of clinical parameters on the expression of LAP and GARP by lymphocytes showed that patients with calreticulin (CALR)mut MPN have increased expression compared with HD and patients with the Januskinase2 (JAK2) mutation. The fraction of lymphocytes bound to activated platelets (aPLT) strongly correlate to LAP and GARP expression suggesting that it is not the lymphocytes themselves but aPLT, which confer the increased expression of GARP and LAP on MPN patient lymphocytes. Notably, no differences in neither platelet counts nor anti‐thrombotic therapy was identified between patients with JAK2‐ and CALRmut patients. Analysis of platelet gene expression failed to identify differences in expression of relevant genes between JAK2‐ and CALRmut patients. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood

Author

Zheng, Yan, Huang, Tao, Wang, Tiange, Mei, Zhendong, Sun, Zhonghan, Zhang, Tao, Ellervik, Christina, Chai, Jin-Fang, Sim, Xueling, van Dam, Rob M., Tai, E-Shyong, Koh, Woon-Puay, Dorajoo, Rajkumar, Saw, Seang-Mei, Sabanayagam, Charumathi, Wong, Tien Yin, Gupta, Preeti, Rossing, Peter, Ahluwalia, Tarunveer S., Vinding, Rebecca K., Bisgaard, Hans, Bønnelykke, Klaus, Wang, Yujie, Graff, Mariaelisa, Voortman, Trudy, van Rooij, Frank J. A., Hofman, Albert, van Heemst, Diana, Noordam, Raymond, Estampador, Angela C., Varga, Tibor V., Enzenbach, Cornelia, Scholz, Markus, Thiery, Joachim, Burkhardt, Ralph, Orho-Melander, Marju, Schulz, Christina-Alexandra, Ericson, Ulrika, Sonestedt, Emily, Kubo, Michiaki, Akiyama, Masato, Zhou, Ang, Kilpeläinen, Tuomas O., Hansen, Torben, Kleber, Marcus E., Delgado, Graciela, McCarthy, Mark, Lemaitre, Rozenn N., Felix, Janine F., Jaddoe, Vincent W. V., Wu, Ying, Mohlke, Karen L., Lehtimäki, Terho, Wang, Carol A., Pennell, Craig E., Schunkert, Heribert, Kessler, Thorsten, Zeng, Lingyao, Willenborg, Christina, Peters, Annette, Lieb, Wolfgang, Grote, Veit, Rzehak, Peter, Koletzko, Berthold, Erdmann, Jeanette, Munz, Matthias, Wu, Tangchun, He, Meian, Yu, Caizheng, Lecoeur, Cécile, Froguel, Philippe, Corella, Dolores, Moreno, Luis A., Lai, Chao-Qiang, Pitkänen, Niina, Boreham, Colin A., Ridker, Paul M., Rosendaal, Frits R., de Mutsert, Renée, Power, Chris, Paternoster, Lavinia, Sørensen, Thorkild I. A., Tjønneland, Anne, Overvad, Kim, Djousse, Luc, Rivadeneira, Fernando, Lee, Nanette R., Raitakari, Olli T., Kähönen, Mika, Viikari, Jorma, Langhendries, Jean-Paul, Escribano, Joaquin, Verduci, Elvira, Dedoussis, George, König, Inke, Balkau, Beverley, Coltell, Oscar, Dallongeville, Jean, Meirhaeghe, Aline, Amouyel, Philippe, Gottrand, Frédéric, Pahkala, Katja, Niinikoski, Harri, Hyppönen, Elina, März, Winfried, Mackey, David A., Gruszfeld, Dariusz, Tucker, Katherine L., Fumeron, Frédéric, Estruch, Ramon, Ordovas, Jose M., Arnett, Donna K., Mook-Kanamori, Dennis O., Mozaffarian, Dariush, Psaty, Bruce M., North, Kari E., Chasman, Daniel I., and Qi, Lu

Published
2020

33. DeepFake electrocardiograms using generative adversarial networks are the beginning of the end for privacy issues in medicine

Author

Thambawita, Vajira, Isaksen, Jonas L., Hicks, Steven A., Ghouse, Jonas, Ahlberg, Gustav, Linneberg, Allan, Grarup, Niels, Ellervik, Christina, Olesen, Morten Salling, Hansen, Torben, Graff, Claus, Holstein-Rathlou, Niels-Henrik, Strümke, Inga, Hammer, Hugo L., Maleckar, Mary M., Halvorsen, Pål, Riegler, Michael A., and Kanters, Jørgen K.

Published
2021
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36. Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals

Author

Noordam, Raymond, Young, William J., Salman, Reem, Kanters, Jørgen K., van den Berg, Marten E., van Heemst, Diana, Lin, Henry J., Barreto, Sandhi Maria, Biggs, Mary L., Biino, Ginevra, Catamo, Eulalia, Concas, Maria Pina, Ding, Jun, Evans, Daniel S., Foco, Luisa, Grarup, Niels, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Mei, Hao, van der Most, Peter J., Müller-Nurasyid, Martina, Nelson, Christopher P., Qian, Yong, Repetto, Linda, Said, M. Abdullah, Shah, Nabi, Schramm, Katharina, Vidigal, Pedro G., Weiss, Stefan, Yao, Jie, Zilhao, Nuno R., Brody, Jennifer A., Braund, Peter S., Brumat, Marco, Campana, Eric, Christofidou, Paraskevi, Caulfield, Mark J., De Grandi, Alessandro, Dominiczak, Anna F., Doney, Alex S.F., Eiriksdottir, Gudny, Ellervik, Christina, Giatti, Luana, Gögele, Martin, Graff, Claus, Guo, Xiuqing, van der Harst, Pim, Joshi, Peter K., Kähönen, Mika, Kestenbaum, Bryan, Lima-Costa, Maria F., Linneberg, Allan, Maan, Arie C., Meitinger, Thomas, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Petersmann, Astrid, Sever, Peter, Sinner, Mortiz F., Shen, Xia, Stanton, Alice, Strauch, Konstantin, Soliman, Elsayed Z., Tarasov, Kirill V., Taylor, Kent D., Thio, Chris H.L., Uitterlinden, André G., Vaccargiu, Simona, Waldenberger, Melanie, Robino, Antonietta, Correa, Adolfo, Cucca, Francesco, Cummings, Steven R., Dörr, Marcus, Girotto, Giorgia, Gudnason, Vilmundur, Hansen, Torben, Heckbert, Susan R., Juhl, Christian R., Kääb, Stefan, Lehtimäki, Terho, Liu, Yongmei, Lotufo, Paulo A., Palmer, Colin N.A., Pirastu, Mario, Pramstaller, Peter P., Ribeiro, Antonio Luiz P., Rotter, Jerome I., Samani, Nilesh J., Snieder, Harold, Spector, Tim D., Stricker, Bruno H., Verweij, Niek, Wilson, James F., Wilson, James G., Jukema, J. Wouter, Tinker, Andrew, Newton-Cheh, Christopher H., Sotoodehnia, Nona, Mook-Kanamori, Dennis O., Munroe, Patricia B., and Warren, Helen R.

Published
2019
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39. Oxidative Stress-Induced Damage to RNA and DNA and Mortality in Individuals with Psychiatric Illness.

Author

Jorgensen, Anders, Brandslund, Ivan, Ellervik, Christina, Henriksen, Trine, Weimann, Allan, Andersen, Mikkel Porsborg, Torp-Pedersen, Christian, Andersen, Per Kragh, Jorgensen, Martin Balslev, and Poulsen, Henrik Enghusen

Subjects
DNA adducts, LIQUID chromatography-mass spectrometry, PROPORTIONAL hazards models, DNA damage, NUCLEIC acids, MORTALITY
Abstract

Key Points: Question: Is systemic oxidative stress-induced damage to RNA and DNA increased in community-dwelling individuals with psychiatric illness and associated with all-cause mortality? Findings: In this cohort study, oxidative stress-induced damage to RNA was increased in individuals with psychiatric illness and showed a dose-response association with mortality. Meaning: The findings suggest that RNA damage from oxidation may be a mechanism in the accelerated aging observed in psychiatric illness and could have utility as a marker of mortality risk in these common disorders. This cohort study evaluates the association between oxidative stress on nucleic acids and all-cause mortality in individuals with and without psychiatric illness. Importance: All-cause mortality and the risk for age-related medical disease is increased in individuals with psychiatric illness, but the underlying biological mechanisms are not known. Oxidative stress on nucleic acids (DNA and RNA; NA-OXS) is a molecular driver of aging and a potential pathophysiological mechanism in a range of age-related disorders. Objective: To study the levels of markers of NA-OXS in a large cohort of community-dwelling individuals with and without psychiatric illness and to evaluate their association with prospective all-cause mortality. Design, Setting, and Participants: This cohort study used a combined cohort of participants from 2 population-based health studies: the Danish General Suburban Population Study (January 2010 to October 2013) and nondiabetic control participants from the Vejle Diabetes Biobank study (March 2007 to May 2010). Individual history of psychiatric illness was characterized using register data on psychiatric diagnoses and use of psychotropic drugs before baseline examination. Urinary markers of systemic RNA (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]) damage from oxidation were measured by ultraperformance liquid chromatography–tandem mass spectrometry. Cox proportional hazard regression models were applied for survival analyses, using register-based all-cause mortality updated to May 2023. The follow-up time was up to 16.0 years. Exposures: History of psychiatric illness. Main Outcomes and Measures: Mortality risk according to psychiatric illness status and 8-oxoGuo or 8-oxodG excretion level. Results: A total of 7728 individuals were included (3983 [51.5%] female; mean [SD] age, 58.6 [11.9] years), 3095 of whom (40.0%) had a history of psychiatric illness. Mean (SD) baseline 8-oxoGuo was statistically significantly higher in individuals with psychiatric illness than in those without (2.4 [1.2] nmol/mmol vs 2.2 [0.9] nmol/mmol; P <.001), whereas 8-oxodG was not. All-cause mortality was higher in the psychiatric illness group vs the no psychiatric illness group (hazard ratio [HR], 1.44; 95% CI, 1.27-1.64; P <.001) and increased sequentially with each increasing tertile of 8-oxoGuo excretion in both groups to an almost doubled risk in the psychiatric illness/high 8-oxoGuo group compared to the no psychiatric illness/low 8-oxoGuo reference group (HR, 1.99; 95% CI, 1.58-2.52; P <.001). These results persisted after adjustment for a range of potential confounders and in a sensitivity analysis stratified for sex. Conclusions and Relevance: This study establishes systemic oxidative stress-induced damage to RNA as a potential mechanism in the accelerated aging observed in psychiatric disorders and urinary 8-oxoGuo as a potentially useful marker of mortality risk in individuals with psychiatric illness. [ABSTRACT FROM AUTHOR]

Published
2024
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40. JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms.

Author

Eickhardt‐Dalbøge, Christina Schjellerup, Nielsen, Henrik V., Fuursted, Kurt, Stensvold, Christen Rune, Andersen, Lee O' Brien, Lilje, Berit, Larsen, Morten Kranker, Kjær, Lasse, Christensen, Sarah Friis, Knudsen, Trine Alma, Skov, Vibe, Sørensen, Anders Lindholm, Ellervik, Christina, Olsen, Lars Rønn, Christensen, Jens Jørgen Elmer, Nielsen, Xiaohui Chen, Hasselbalch, Hans Carl, and Ingham, Anna Cäcilia

Subjects
GUT microbiome, MYELOPROLIFERATIVE neoplasms, MYELOFIBROSIS, POLYCYTHEMIA vera, NUCLEOTIDE sequencing, INFECTION control
Abstract

Background: Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are myeloproliferative neoplasms (MPN). Inflammation is involved in the initiation, progression, and symptomology of the diseases. The gut microbiota impacts the immune system, infection control, and steady‐state hematopoiesis. Methods: We analyzed the gut microbiota of 227 MPN patients and healthy controls (HCs) using next‐generation sequencing. We expanded our previous results in PV and ET patients with additional PV, pre‐MF, and MF patients which allowed us to compare MPN patients collectively, MPN sub‐diagnoses, and MPN mutations (separately and combined) vs. HCs (N = 42) and compare within MPN sub‐diagnoses and MPN mutation. Results: MPN patients had a higher observed richness (median, 245 [range, 49–659]) compared with HCs (191.5 [range, 111–300; p =.003]) and a lower relative abundance of taxa within the Firmicutes phylum; for example, Faecalibacterium (6% vs. 14%, p <.001). The microbiota of CALR‐positive patients (N = 30) resembled that of HCs more than that of patients with JAK2V617F (N = 177). In JAK2V617F‐positive patients, only minor differences in the gut microbiota were observed between MPN sub‐diagnoses, illustrating the importance of this mutation. Conclusion: The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more. [ABSTRACT FROM AUTHOR]

Published
2024
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