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1,166 results on '"Van Heemst, Diana"'

2. The performance of metabolomics-based prediction scores for mortality in older patients with solid tumors

Author

van Holstein, Yara, Mooijaart, Simon P., van Oevelen, Mathijs, van Deudekom, Floor J., Vojinovic, Dina, Bizzarri, Daniele, van den Akker, Erik B., Noordam, Raymond, Deelen, Joris, van Heemst, Diana, de Glas, Nienke A., Holterhues, Cynthia, Labots, Geert, van den Bos, Frederiek, Beekman, Marian, Slagboom, P. Eline, van Munster, Barbara C., Portielje, Johanneke E. A., and Trompet, Stella

Published
2024
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4. 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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6. An Internet-Based Physical Activity Intervention to Improve Quality of Life of Inactive Older Adults: A Randomized Controlled Trial

Author

Broekhuizen, Karen, de Gelder, Jelle, Wijsman, Carolien A, Wijsman, Liselotte W, Westendorp, Rudi GJ, Verhagen, Evert, Slagboom, Pieternella E, de Craen, Anton J, van Mechelen, Willem, van Heemst, Diana, van der Ouderaa, Frans, and Mooijaart, Simon P

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundIncreasing physical activity is a viable strategy for improving both the health and quality of life of older adults. ObjectiveThe aim of this study was to assess if an Internet-based intervention aimed to increase physical activity was effective in improving quality of life of inactive older adults. In addition, we analyzed the effect of the intervention on quality of life among those participants who successfully reached their individually targeted increase in daily physical activity as indicated by the intervention program, as well as the dose-response effect of increasing physical activity on quality of life. MethodsThe intervention was tested in a randomized controlled trial and was comprised of an Internet program—DirectLife (Philips)—aimed at increasing physical activity using monitoring and feedback by accelerometry and feedback by digital coaching (n=119). The control group received no intervention (n=116). Participants were inactive 60-70-year-olds and were recruited from the general population. Quality of life and physical activity were measured at baseline and after 3 months using the Research ANd Development 36-item health survey (RAND-36) and wrist-worn triaxial accelerometer, respectively. ResultsAfter 3 months, a significant improvement in quality of life was seen in the intervention group compared to the control group for RAND-36 subscales on emotional and mental health (2.52 vs -0.72, respectively; P=.03) and health change (8.99 vs 2.03, respectively; P=.01). A total of 50 of the 119 participants (42.0%) in the intervention group successfully reached their physical activity target and showed a significant improvement in quality of life compared to the control group for subscales on emotional and mental health (4.31 vs -0.72, respectively; P=.009) and health change (11.06 vs 2.03, respectively; P=.004). The dose-response analysis showed that there was a significant association between increase in minutes spent in moderate-to-vigorous physical activity (MVPA) and increase in quality of life. ConclusionsOur study shows that an Internet-based physical activity program was effective in improving quality of life in 60-70-year-olds after 3 months, particularly in participants that reached their individually targeted increase in daily physical activity. Trial RegistrationNederlands Trial Register: NTR 3045; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3045 (Archived by WebCite at http://www.webcitation.org/6fobg2sjJ)

Published
2016
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9. Dose-Response Effects of a Web-Based Physical Activity Program on Body Composition and Metabolic Health in Inactive Older Adults: Additional Analyses of a Randomized Controlled Trial

Author

Vroege, David P, Wijsman, Carolien A, Broekhuizen, Karen, de Craen, Anton JM, van Heemst, Diana, van der Ouderaa, Frans JG, van Mechelen, Willem, Slagboom, P Eline, Catt, Michael, Westendorp, Rudi GJ, Verhagen, Evert ALM, and Mooijaart, Simon P

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundLow physical activity is a major risk factor for several age-related diseases. Recently, we showed in a randomized controlled trial that a 12-week Web-based intervention (Philips DirectLife) to increase physical activity was effective in increasing physical activity levels and metabolic health in an inactive population aged 60-70 years. ObjectiveThe goal of this paper was to assess how many participants successfully reached the physical activity level as targeted by the intervention and what the effects of the intervention on body composition and metabolic health in these successful individuals were to provide insight in the maximum attainable effect of the intervention. MethodsAmong the 235 participants in a randomized controlled trial of the Actief en Gezond Oud (AGO) study, we assessed the effects of the intervention on metabolic parameters in those who had successfully reached their personalized physical activity target compared with the entire intervention group. Furthermore, we studied the dose-response effect of increase in physical activity on metabolic outcome within the intervention group. ResultsOf the intervention group, 50 of 119 (42.0%) participants successfully reached the physical activity target (corresponding to a 10% increased daily physical activity on average). This group showed markedly higher effects of the intervention compared to the entire intervention group, with greater decreases in body weight (2.74 vs 1.49 kg), waist circumference (3.74 vs 2.33 cm), insulin resistance (HOMA index: 0.23 vs 0.20), and in cholesterol/HDL ratio (0.39 vs 0.20) and Framingham risk score (0.90% vs 0.54%). We found that men compared to women were more likely to be successful. The dose-response analysis showed that there was a significant association between increase in minutes spent in moderate-to-vigorous activity and body weight loss, BMI reduction, waist circumference reduction, HDL cholesterol increasing, and cholesterol/HDL ratio lowering. ConclusionsOf the intervention group, 42.0% (50/119) reached their daily physical activity end goal, which was associated with a markedly better effect on body composition and metabolic health compared to the effect in the entire intervention group. In this population, men are more likely to be successful in increasing physical activity. Findings demonstrate that improving the effect of such physical activity interventions requires finding new ways to increase the proportion of the population reaching the targeted goal. Trial RegistrationDutch Trial Registry: NTR 3045; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3045 (Archived by WebCite at http://www.webcitation.org/6KPw52dCc).

Published
2014
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10. Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials

Author

Lyko, Christina, Blum, Manuel R, Abolhassani, Nazanin, Stuber, Mirah J, Del Giovane, Cinzia, Feller, Martin, Moutzouri, Elisavet, Oberle, Jolanda, Jungo, Katharina T, Collet, Tinh‐Hai, Elzen, Wendy PJ den, Poortvliet, Rosalinde KE, Du Puy, Robert S, Dekkers, Olaf M, Trompet, Stella, Jukema, J Wouter, Aujesky, Drahomir, Quinn, Terry, Westendorp, Rudi, Kearney, Patricia M, Gussekloo, Jacobijn, Van Heemst, Diana, Mooijaart, Simon P, Bauer, Douglas C, and Rodondi, Nicolas

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Female, Humans, Aged, Male, Thyroxine, Randomized Controlled Trials as Topic, Hypothyroidism, Hormone Replacement Therapy, autoimmune thyroid disease, levothyroxine treatment, subclinical hypothyroidism, Cardiovascular System & Hematology, Clinical sciences
Abstract

BackgroundAntithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4).ObjectiveTo determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies.MethodsWe pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire.ResultsAmong 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment.ConclusionsAmong older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

Published
2022

11. The association of inflammatory markers with frailty and in-hospital mortality in older COVID-19 patients

Author

Mooijaart, Simon P., Gussekloo, Jacobijn, Polinder-Bos, Harmke A., Moons, Karel G.M., van Smeden, Maarten, Peeters, Geeske, Melis, René J.F., Elders, Petra J.M., Festen, Jan, van der Linden, Carolien M.J., Jansen, Steffy W.M., Willems, Hanna C., van der Bol, Jessica M., Appelman, Brent, Rusch, Daisy, van den Oever, Niels C. Gritters, Simsek, Suat, van Osch, Frits H.M., de Kruif, Martijn D., Douma, Renée A., Moeniralam, Hazra, Brinkman, Kees, Bokhizzou, Nejma, Leavis, Helen, Beudel, Martijn, Abbink, Evertine J., Jacobs-Peters, Jeannette, Dofferhoff, Ton, Hoogerwerf, Jacobien J., Kerckhoffs, Angele, van der Maat, Josephine, Netea, Mihai, Slieker, Kitty, Veerman, Karin, Tran Van Hoi, Estelle, Mooijaart, Simon, Dalm, Virgil A.S.H., Polinder Bos, Harmke A., van Heemst, Diana, van Raaij, Bas F.M., Noordam, Raymond, Kuranova, Anna, and Smorenberg, Annemieke

Published
2024
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12. Effects of a Web-Based Intervention on Physical Activity and Metabolism in Older Adults: Randomized Controlled Trial

Author

Wijsman, Carolien A, Westendorp, Rudi GJ, Verhagen, Evert ALM, Catt, Michael, Slagboom, P Eline, de Craen, Anton JM, Broekhuizen, Karen, van Mechelen, Willem, van Heemst, Diana, van der Ouderaa, Frans, and Mooijaart, Simon P

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Public aspects of medicine, RA1-1270
Abstract

BackgroundLack of physical activity leads to detrimental changes in body composition and metabolism, functional decline, and increased risk of disease in old age. The potential of Web-assisted interventions for increasing physical activity and improving metabolism in older individuals holds great promise but to our knowledge it has not been studied. ObjectiveThe goal of our study was to assess whether a Web-based intervention increases physical activity and improves metabolic health in inactive older adults. MethodsWe conducted a 3-month randomized, waitlist-controlled trial in a volunteer sample of 235 inactive adults aged 60-70 years without diabetes. The intervention group received the Internet program Philips DirectLife, which was directed at increasing physical activity using monitoring and feedback by accelerometer and digital coaching. The primary outcome was relative increase in physical activity measured objectively using ankle- and wrist-worn accelerometers. Secondary outcomes of metabolic health included anthropometric measures and parameters of glucose metabolism. ResultsIn total, 226 participants (97%) completed the study. At the ankle, activity counts increased by 46% (standard error [SE] 7%) in the intervention group, compared to 12% (SE 3%) in the control group (Pdifference

Published
2013
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14. Metabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome

Author

Costeira, Ricardo, Evangelista, Laila, Wilson, Rory, Yan, Xinyu, Hellbach, Fabian, Sinke, Lucy, Christiansen, Colette, Villicaña, Sergio, Masachs, Olatz M., Tsai, Pei-Chien, Mangino, Massimo, Menni, Cristina, Berry, Sarah E., Beekman, Marian, van Heemst, Diana, Slagboom, P. Eline, Heijmans, Bastiaan T., Suhre, Karsten, Kastenmüller, Gabi, Gieger, Christian, Peters, Annette, Small, Kerrin S., Linseisen, Jakob, Waldenberger, Melanie, and Bell, Jordana T.

Published
2023
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16. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Heijmans, Bastiaan, ’t Hoen, Peter, van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret, Pool, René, van Dongen, Jenny, Hottenga, Jouke, van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje, Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Veldink, Jan, van den Berg, Leonard, van Duijn, Cornelia, Hofman, Bert, Isaacs, Aaron, Uitterlinden, André, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha, van ‘t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon, Swertz, Morris, van Zwet, Erik, Hoang, Thanh T., Lee, Yunsung, McCartney, Daniel L., Kersten, Elin T.G., Page, Christian M., Hulls, Paige M., Lee, Mikyeong, Walker, Rosie M., Breeze, Charles E., Bennett, Brian D., Burkholder, Adam B., Ward, James, Brantsæter, Anne Lise, Caspersen, Ida H., Motsinger-Reif, Alison A., Richards, Marie, White, Julie D., Zhao, Shanshan, Richmond, Rebecca C., Magnus, Maria C., Koppelman, Gerard H., Evans, Kathryn L., Marioni, Riccardo E., Håberg, Siri E., and London, Stephanie J.

Published
2024
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17. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Author

Mathieson, Iain, Day, Felix R., Barban, Nicola, Tropf, Felix C., Brazel, David M., Vaez, Ahmad, van Zuydam, Natalie, Bitarello, Bárbara D., Gardner, Eugene J., Akimova, Evelina T., Azad, Ajuna, Bergmann, Sven, Bielak, Lawrence F., Boomsma, Dorret I., Bosak, Kristina, Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey Smith, George, Davies, Gail, Deary, Ian J., Esko, Tõnu, Faul, Jessica D., Franco, Oscar, Ganna, Andrea, Gaskins, Audrey J., Gelemanovic, Andrea, de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Gopinath, Bamini, Grabe, Hans Jörgen, Gunderson, Erica P., Hayward, Caroline, He, Chunyan, van Heemst, Diana, Hill, W. David, Hoffmann, Eva R., Homuth, Georg, Hottenga, Jouke Jan, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Jansen, Rick, Johannesson, Magnus, Kamali, Zoha, Kardia, Sharon L. R., Kavousi, Maryam, Kifley, Annette, Kiiskinen, Tuomo, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Liew, Gerald, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Milani, Lili, Missmer, Stacey A., Mitchell, Paul, Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nauck, Matthias, Nolte, Ilja M., Noordam, Raymond, Penninx, Brenda W. J. H., Peters, Annette, Peyser, Patricia A., Polašek, Ozren, Power, Chris, Pribisalic, Ajka, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Shukla, Vallari, Smith, Jennifer A., Stankovic, Stasa, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Uitterlinden, André G., Waldenberger, Melanie, Wareham, Nicholas J., Weir, David R., Willemsen, Gonneke, Zhao, Jing Hau, Zhao, Wei, Zhao, Yajie, Snieder, Harold, den Hoed, Marcel, Ong, Ken K., Mills, Melinda C., and Perry, John R. B.

Published
2023
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26. A meta-analysis of genome-wide association studies identifies multiple longevity genes.

Author

Deelen, Joris, Evans, Daniel S, Arking, Dan E, Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K, Biggs, Mary L, van der Spek, Ashley, Atzmon, Gil, Ware, Erin B, Sarnowski, Chloé, Smith, Albert V, Seppälä, Ilkka, Cordell, Heather J, Dose, Janina, Amin, Najaf, Arnold, Alice M, Ayers, Kristin L, Barzilai, Nir, Becker, Elizabeth J, Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C, Cubaynes, Sarah, Cummings, Steven R, Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D, Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B, Huisman, Martijn, Hurme, Mikko A, Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon LR, Kingston, Andrew, Kirkwood, Thomas BL, Launer, Lenore J, Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B, Nie, Chao, Nohr, Ellen A, Orwoll, Eric S, Perls, Thomas T, Province, Michael A, Psaty, Bruce M, Raitakari, Olli T, Reinders, Marcel JT, Robine, Jean-Marie, Rotter, Jerome I, Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild IA, Taylor, Kent D, Uitterlinden, André G, van der Flier, Wiesje, van der Lee, Sven J, van Duijn, Cornelia M, van Heemst, Diana, Vaupel, James W, Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P, Lunetta, Kathryn L, Slagboom, P Eline, and Murabito, Joanne M

Subjects
Humans, Heat-Shock Proteins, Longevity, Apolipoprotein E2, Apolipoprotein E4, Genome-Wide Association Study
Abstract

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Published
2019

27. A genome-wide association study identifies genetic loci associated with specific lobar brain volumes

Author

van der Lee, Sven J, Knol, Maria J, Chauhan, Ganesh, Satizabal, Claudia L, Smith, Albert Vernon, Hofer, Edith, Bis, Joshua C, Hibar, Derrek P, Hilal, Saima, van den Akker, Erik B, Arfanakis, Konstantinos, Bernard, Manon, Yanek, Lisa R, Amin, Najaf, Crivello, Fabrice, Cheung, Josh W, Harris, Tamara B, Saba, Yasaman, Lopez, Oscar L, Li, Shuo, van der Grond, Jeroen, Yu, Lei, Paus, Tomas, Roshchupkin, Gennady V, Amouyel, Philippe, Jahanshad, Neda, Taylor, Kent D, Yang, Qiong, Mathias, Rasika A, Boehringer, Stefan, Mazoyer, Bernard, Rice, Ken, Cheng, Ching Yu, Maillard, Pauline, van Heemst, Diana, Wong, Tien Yin, Niessen, Wiro J, Beiser, Alexa S, Beekman, Marian, Zhao, Wanting, Nyquist, Paul A, Chen, Christopher, Launer, Lenore J, Psaty, Bruce M, Ikram, M Kamran, Vernooij, Meike W, Schmidt, Helena, Pausova, Zdenka, Becker, Diane M, De Jager, Philip L, Thompson, Paul M, van Duijn, Cornelia M, Bennett, David A, Slagboom, P Eline, Schmidt, Reinhold, Longstreth, WT, Ikram, M Arfan, Seshadri, Sudha, Debette, Stéphanie, Gudnason, Vilmundur, Adams, Hieab HH, and DeCarli, Charles

Subjects
Biological Sciences, Genetics, Neurosciences, Mental Health, Brain Disorders, Human Genome, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Frontal Lobe, Gene Expression Regulation, Developmental, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Genotype, Heredity, Humans, Magnetic Resonance Imaging, Occipital Lobe, Organ Size, Parietal Lobe, Phenotype, Temporal Lobe, United Kingdom, Biomarkers, Genome-wide association studies, Neurology, Biological sciences, Biomedical and clinical sciences
Abstract

Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications (DAAM1 and THBS3), or close to genes causing Mendelian brain-related diseases (ZIC4 and FGFRL1). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.

Published
2019

28. Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: A nested study within a randomized placebo controlled trial

Author

Büchi, Annina Elisabeth, Feller, Martin, Netzer, Seraina, Blum, Manuel R., Gonzalez Rodriguez, Elena, Collet, Tinh-Hai, Del Giovane, Cinzia, van Heemst, Diana, Quinn, Terry, Kearney, Patricia M., Westendorp, Rudi G.J., Gussekloo, Jacobijn, Mooijaart, Simon P., Hans, Didier, Bauer, Douglas C., Rodondi, Nicolas, and Aeberli, Daniel

Published
2022
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31. Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants.

Author

Young, William J., van der Most, Peter J., Bartz, Traci M., Bos, Maxime M., Biino, Ginevra, ThuyVy Duong, Foco, Luisa, Lominchar, Jesus T., Nurasyid, Martina Müller, Nardone, Giuseppe Giovanni, Pecori, Alessandro, Ramirez, Julia, Repetto, Linda, Schramm, Katharina, Shen, Xia, van Duijvenboden, Stefan, van Heemst, Diana, Weiss, Stefan, Jie Yao, and Benjamins, Jan-Walter

Published
2024
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33. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation

Author

Richard, Melissa A, Huan, Tianxiao, Ligthart, Symen, Gondalia, Rahul, Jhun, Min A, Brody, Jennifer A, Irvin, Marguerite R, Marioni, Riccardo, Shen, Jincheng, Tsai, Pei-Chien, Montasser, May E, Jia, Yucheng, Syme, Catriona, Salfati, Elias L, Boerwinkle, Eric, Guan, Weihua, Mosley, Thomas H, Bressler, Jan, Morrison, Alanna C, Liu, Chunyu, Mendelson, Michael M, Uitterlinden, André G, van Meurs, Joyce B, Consortium, BIOS, Heijmans, Bastiaan T, Hoen, Peter AC ’t, van Meurs, Joyce, Isaacs, Aaron, Jansen, Rick, Franke, Lude, Boomsma, Dorret I, Pool, René, van Dongen, Jenny, Hottenga, Jouke J, van Greevenbroek, Marleen MJ, Stehouwer, Coen DA, van der Kallen, Carla JH, Schalkwijk, Casper G, Wijmenga, Cisca, Zhernakova, Alexandra, Tigchelaar, Ettje F, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H, van den Berg, Leonard H, van Duijn, Cornelia M, Hofman, Albert, Jhamai, P Mila, Verbiest, Michael, Suchiman, H Eka D, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, van ’t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Zhernakova, Dasha V, Luijk, René, Bonder, Marc Jan, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M, Swertz, Morris A, van Zwet, Erik W, Franco, Oscar H, Zhang, Guosheng, Li, Yun, Stewart, James D, Bis, Joshua C, Psaty, Bruce M, Chen, Yii-Der Ida, Kardia, Sharon LR, Zhao, Wei, Turner, Stephen T, Absher, Devin, Aslibekyan, Stella, Starr, John M, McRae, Allan F, Hou, Lifang, Just, Allan C, Schwartz, Joel D, Vokonas, Pantel S, Menni, Cristina, Spector, Tim D, Shuldiner, Alan, Damcott, Coleen M, Rotter, Jerome I, Palmas, Walter, Liu, Yongmei, and Paus, Tomáš

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Aged, Blood Pressure, CpG Islands, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Genetic Variation, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Middle Aged, Nerve Tissue Proteins, Quantitative Trait Loci, Tetraspanins, BIOS Consortium, DNA methylation, Mendelian randomization, blood pressure, epigenome-wide association study, gene expression, sequence variation, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p  30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Published
2017

36. 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

37. Multi-ancestry genome-wide gene–sleep interactions identify novel loci for blood pressure

Author

Wang, Heming, Noordam, Raymond, Cade, Brian E., Schwander, Karen, Winkler, Thomas W., Lee, Jiwon, Sung, Yun Ju, Bentley, Amy R., Manning, Alisa K., Aschard, Hugues, Kilpeläinen, Tuomas O., Ilkov, Marjan, Brown, Michael R., Horimoto, Andrea R., Richard, Melissa, Bartz, Traci M., Vojinovic, Dina, Lim, Elise, Nierenberg, Jovia L., Liu, Yongmei, Chitrala, Kumaraswamynaidu, Rankinen, Tuomo, Musani, Solomon K., Franceschini, Nora, Rauramaa, Rainer, Alver, Maris, Zee, Phyllis C., Harris, Sarah E., van der Most, Peter J., Nolte, Ilja M., Munroe, Patricia B., Palmer, Nicholette D., Kühnel, Brigitte, Weiss, Stefan, Wen, Wanqing, Hall, Kelly A., Lyytikäinen, Leo-Pekka, O’Connell, Jeff, Eiriksdottir, Gudny, Launer, Lenore J., de Vries, Paul S., Arking, Dan E., Chen, Han, Boerwinkle, Eric, Krieger, Jose E., Schreiner, Pamela J., Sidney, Stephen, Shikany, James M., Rice, Kenneth, Chen, Yii-Der Ida, Gharib, Sina A., Bis, Joshua C., Luik, Annemarie I., Ikram, M. Arfan, Uitterlinden, André G., Amin, Najaf, Xu, Hanfei, Levy, Daniel, He, Jiang, Lohman, Kurt K., Zonderman, Alan B., Rice, Treva K., Sims, Mario, Wilson, Gregory, Sofer, Tamar, Rich, Stephen S., Palmas, Walter, Yao, Jie, Guo, Xiuqing, Rotter, Jerome I., Biermasz, Nienke R., Mook-Kanamori, Dennis O., Martin, Lisa W., Barac, Ana, Wallace, Robert B., Gottlieb, Daniel J., Komulainen, Pirjo, Heikkinen, Sami, Mägi, Reedik, Milani, Lili, Metspalu, Andres, Starr, John M., Milaneschi, Yuri, Waken, R. J., Gao, Chuan, Waldenberger, Melanie, Peters, Annette, Strauch, Konstantin, Meitinger, Thomas, Roenneberg, Till, Völker, Uwe, Dörr, Marcus, Shu, Xiao-Ou, Mukherjee, Sutapa, Hillman, David R., Kähönen, Mika, Wagenknecht, Lynne E., Gieger, Christian, Grabe, Hans J., Zheng, Wei, Palmer, Lyle J., Lehtimäki, Terho, Gudnason, Vilmundur, Morrison, Alanna C., Pereira, Alexandre C., Fornage, Myriam, Psaty, Bruce M., van Duijn, Cornelia M., Liu, Ching-Ti, Kelly, Tanika N., Evans, Michele K., Bouchard, Claude, Fox, Ervin R., Kooperberg, Charles, Zhu, Xiaofeng, Lakka, Timo A., Esko, Tõnu, North, Kari E., Deary, Ian J., Snieder, Harold, Penninx, Brenda W. J. H., Gauderman, W. James, Rao, Dabeeru C., Redline, Susan, and van Heemst, Diana

Published
2021
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39. A genome-wide interaction analysis of tricyclic/tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium

Author

Noordam, Raymond, Sitlani, Colleen M, Avery, Christy L, Stewart, James D, Gogarten, Stephanie M, Wiggins, Kerri L, Trompet, Stella, Warren, Helen R, Sun, Fangui, Evans, Daniel S, Li, Xiaohui, Li, Jin, Smith, Albert V, Bis, Joshua C, Brody, Jennifer A, Busch, Evan L, Caulfield, Mark J, Chen, Yii-Der I, Cummings, Steven R, Cupples, L Adrienne, Duan, Qing, Franco, Oscar H, Méndez-Giráldez, Rául, Harris, Tamara B, Heckbert, Susan R, van Heemst, Diana, Hofman, Albert, Floyd, James S, Kors, Jan A, Launer, Lenore J, Li, Yun, Li-Gao, Ruifang, Lange, Leslie A, Lin, Henry J, de Mutsert, Renée, Napier, Melanie D, Newton-Cheh, Christopher, Poulter, Neil, Reiner, Alexander P, Rice, Kenneth M, Roach, Jeffrey, Rodriguez, Carlos J, Rosendaal, Frits R, Sattar, Naveed, Sever, Peter, Seyerle, Amanda A, Slagboom, P Eline, Soliman, Elsayed Z, Sotoodehnia, Nona, Stott, David J, Stürmer, Til, Taylor, Kent D, Thornton, Timothy A, Uitterlinden, André G, Wilhelmsen, Kirk C, Wilson, James G, Gudnason, Vilmundur, Jukema, J Wouter, Laurie, Cathy C, Liu, Yongmei, Mook-Kanamori, Dennis O, Munroe, Patricia B, Rotter, Jerome I, Vasan, Ramachandran S, Psaty, Bruce M, Stricker, Bruno H, and Whitsel, Eric A

Subjects
Pharmacology and Pharmaceutical Sciences, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Health Disparities, Human Genome, Minority Health, Cardiovascular, Heart Disease, Good Health and Well Being, Aged, Aging, Antidepressive Agents, Tricyclic, Electrocardiography, Female, Genetic Loci, Genome-Wide Association Study, Heart, Humans, Male, Middle Aged, Pharmacogenetics, Genome-wide, QT interval electrocardiography, RR interval, drug-gene interaction, tri/tetracyclic antidepressants, Medical and Health Sciences, Genetics & Heredity, Clinical sciences
Abstract

BackgroundIncreased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/tetracyclic antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals.Methods and resultsWe conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates. Among the populations of European ancestry, two genome-wide significant loci were identified for RR interval: rs6737205 in BRE (β=56.3, pinteraction=3.9e-9) and rs9830388 in UBE2E2 (β=25.2, pinteraction=1.7e-8). In Hispanic/Latino cohorts, rs2291477 in TGFBR3 significantly modified the association between TCAs and QT intervals (β=9.3, pinteraction=2.55e-8). In the meta-analyses of the other ethnicities, these loci either were excluded from the meta-analyses (as part of quality control), or their effects did not reach the level of nominal statistical significance (pinteraction>0.05). No new variants were identified in these ethnicities. No additional loci were identified after inverse-variance-weighted meta-analysis of the three ancestries.ConclusionsAmong Europeans, TCA interactions with variants in BRE and UBE2E2 were identified in relation to RR intervals. Among Hispanic/Latinos, variants in TGFBR3 modified the relation between TCAs and QT intervals. Future studies are required to confirm our results.

Published
2017

41. 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, Medici, Marco, 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

Abstract

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Published
2024

42. Incidence and determinants of spontaneous normalization of subclinical hypothyroidism in older adults

Author

van der Spoel, Evie, van Vliet, Nicolien A, Poortvliet, Rosalinde K E, Du Puy, Robert S, den Elzen, Wendy P J, Quinn, Terence J, Stott, David J, Sattar, Naveed, Kearney, Patricia M, Blum, Manuel R, Alwan, Heba, Rodondi, Nicolas, Collet, Tinh-Hai, Westendorp, Rudi G J, Ballieux, Bart E, Jukema, J Wouter, Dekkers, Olaf M, Gussekloo, Jacobijn, Mooijaart, Simon P, van Heemst, Diana, van der Spoel, Evie, van Vliet, Nicolien A, Poortvliet, Rosalinde K E, Du Puy, Robert S, den Elzen, Wendy P J, Quinn, Terence J, Stott, David J, Sattar, Naveed, Kearney, Patricia M, Blum, Manuel R, Alwan, Heba, Rodondi, Nicolas, Collet, Tinh-Hai, Westendorp, Rudi G J, Ballieux, Bart E, Jukema, J Wouter, Dekkers, Olaf M, Gussekloo, Jacobijn, Mooijaart, Simon P, and van Heemst, Diana

Abstract

Context With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. Objective To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism. Design Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial). Setting Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. Participants The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. Main Outcome Measures Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. Results In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. Conclusion Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism, CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown.OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of thyroid-stimulating hormone (TSH) levels in older adults with subclinical hypothyroidism.DESIGN: Pooled data were used from the (i) pre-trial population, and (ii) in-trial placebo group from two randomized, double-blind, placebo-controlled trials (TRUST and IEMO thyroid 80-plus thyroid trial).SETTING: Community-dwelling 65 + adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom.PARTICIPANTS: The pre-trial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free thyroxine (fT4) within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included.MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization.RESULTS: In the pre-trial phase, TSH levels normalized in 60.8% of participants in a median follow-up of one year. In the in-trial phase, levels normalized in 39.9% of participants after one year follow-up. Younger age, female sex, lower initial TSH level, higher initial fT4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization.CONCLUSIONS: Since TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment.

Published
2024

43. Lifestyle Risk Score: handling missingness of individual lifestyle components in meta-analysis of gene-by-lifestyle interactions

Author

Xu, Hanfei, Schwander, Karen, Brown, Michael R., Wang, Wenyi, Waken, R. J., Boerwinkle, Eric, Cupples, L. Adrienne, de las Fuentes, Lisa, van Heemst, Diana, Osazuwa-Peters, Oyomoare, de Vries, Paul S., van Dijk, Ko Willems, Sung, Yun Ju, Zhang, Xiaoyu, Morrison, Alanna C., Rao, D. C., Noordam, Raymond, and Liu, Ching-Ti

Published
2021
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45. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Hoang, Thanh T., primary, Lee, Yunsung, additional, McCartney, Daniel L., additional, Kersten, Elin T.G., additional, Page, Christian M., additional, Hulls, Paige M., additional, Lee, Mikyeong, additional, Walker, Rosie M., additional, Breeze, Charles E., additional, Bennett, Brian D., additional, Burkholder, Adam B., additional, Ward, James, additional, Brantsæter, Anne Lise, additional, Caspersen, Ida H., additional, Motsinger-Reif, Alison A., additional, Richards, Marie, additional, White, Julie D., additional, Zhao, Shanshan, additional, Richmond, Rebecca C., additional, Magnus, Maria C., additional, Koppelman, Gerard H., additional, Evans, Kathryn L., additional, Marioni, Riccardo E., additional, Håberg, Siri E., additional, London, Stephanie J., additional, Heijmans, Bastiaan, additional, ’t Hoen, Peter, additional, van Meurs, Joyce, additional, Jansen, Rick, additional, Franke, Lude, additional, Boomsma, Dorret, additional, Pool, René, additional, van Dongen, Jenny, additional, Hottenga, Jouke, additional, van Greevenbroek, Marleen, additional, Stehouwer, Coen, additional, van der Kallen, Carla, additional, Schalkwijk, Casper, additional, Wijmenga, Cisca, additional, Zhernakova, Sasha, additional, Tigchelaar, Ettje, additional, Slagboom, P. Eline, additional, Beekman, Marian, additional, Deelen, Joris, additional, Van Heemst, Diana, additional, Veldink, Jan, additional, van den Berg, Leonard, additional, van Duijn, Cornelia, additional, Hofman, Bert, additional, Isaacs, Aaron, additional, Uitterlinden, André, additional, Jhamai, P. Mila, additional, Verbiest, Michael, additional, Suchiman, H. Eka, additional, Verkerk, Marijn, additional, van der Breggen, Ruud, additional, van Rooij, Jeroen, additional, Lakenberg, Nico, additional, Mei, Hailiang, additional, van Iterson, Maarten, additional, van Galen, Michiel, additional, Bot, Jan, additional, Zhernakova, Dasha, additional, van ‘t Hof, Peter, additional, Deelen, Patrick, additional, Nooren, Irene, additional, Moed, Matthijs, additional, Vermaat, Martijn, additional, Luijk, René, additional, Bonder, Marc, additional, van Dijk, Freerk, additional, Arindrarto, Wibowo, additional, Kielbasa, Szymon, additional, Swertz, Morris, additional, and van Zwet, Erik, additional

Published
2024
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46. Association of Biological Age with Tumor Microenvironment in Patients with Esophageal Adenocarcinoma

Author

Ravensbergen, Cor, primary, van Holstein, Yara, additional, Hagenaars, Sophie, additional, Crobach, Stijn, additional, Trompet, Stella, additional, Portielje, Johanneke, additional, de Glas, Nienke, additional, van Heemst, Diana, additional, van den Bos, Frederiek, additional, Tollenaar, Rob, additional, Mesker, Wilma, additional, Mooijaart, Simon, additional, and Slingerland, Marije, additional

Published
2024
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47. Genomewide meta‐analysis identifies loci associated with IGF‐I and IGFBP‐3 levels with impact on age‐related traits

Author

Teumer, Alexander, Qi, Qibin, Nethander, Maria, Aschard, Hugues, Bandinelli, Stefania, Beekman, Marian, Berndt, Sonja I, Bidlingmaier, Martin, Broer, Linda, Group, CHARGE Longevity Working, Cappola, Anne, Ceda, Gian Paolo, Chanock, Stephen, Chen, Ming‐Huei, Chen, Tai C, Chen, Yii‐Der Ida, Chung, Jonathan, Del Greco Miglianico, Fabiola, Eriksson, Joel, Ferrucci, Luigi, Friedrich, Nele, Gnewuch, Carsten, Goodarzi, Mark O, Grarup, Niels, Guo, Tingwei, Hammer, Elke, Hayes, Richard B, Hicks, Andrew A, Hofman, Albert, Houwing‐Duistermaat, Jeanine J, Hu, Frank, Hunter, David J, Husemoen, Lise L, Isaacs, Aaron, Jacobs, Kevin B, Janssen, Joop AMJL, Jansson, John‐Olov, Jehmlich, Nico, Johnson, Simon, Juul, Anders, Karlsson, Magnus, Kilpelainen, Tuomas O, Kovacs, Peter, Kraft, Peter, Li, Chao, Linneberg, Allan, Liu, Yongmei, Loos, Ruth JF, Consortium, Body Composition Genetics, Lorentzon, Mattias, Lu, Yingchang, Maggio, Marcello, Magi, Reedik, Meigs, James, Mellström, Dan, Nauck, Matthias, Newman, Anne B, Pollak, Michael N, Pramstaller, Peter P, Prokopenko, Inga, Psaty, Bruce M, Reincke, Martin, Rimm, Eric B, Rotter, Jerome I, Pierre, Aude Saint, Schurmann, Claudia, Seshadri, Sudha, Sjögren, Klara, Slagboom, P Eline, Strickler, Howard D, Stumvoll, Michael, Suh, Yousin, Sun, Qi, Zhang, Cuilin, Svensson, Johan, Tanaka, Toshiko, Tare, Archana, Tönjes, Anke, Uh, Hae‐Won, van Duijn, Cornelia M, van Heemst, Diana, Vandenput, Liesbeth, Vasan, Ramachandran S, Völker, Uwe, Willems, Sara M, Ohlsson, Claes, Wallaschofski, Henri, and Kaplan, Robert C

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Aging, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Cardiovascular, Adult, Female, Gene Expression Regulation, Genome-Wide Association Study, Humans, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Metabolome, Quantitative Trait Loci, Quantitative Trait, Heritable, Regulatory Sequences, Nucleic Acid, aging, genomewide association study, growth hormone axis, IGF-I, IGFBP-3, longevity, CHARGE Longevity Working Group, Body Composition Genetics Consortium, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci.

Published
2016

48. Vitamin D and skin aging

Author

Hamer, Merel A, Noordam, Raymond, Pardo, Luba M, van Heemst, Diana, Gunn, David A, and Nijsten, Tamar

Abstract

BackgroundThe relationship between 25‐hydroxyvitamin D and different phenotypes of skin aging (e.g., wrinkles, pigmented spots, telangiectasia, perceived age) is unclear. We investigated the association between vitamin D levels and skin aging phenotypes in middle‐aged participants from the Rotterdam Study (RS) and Leiden Longevity Study (LLS).MethodsStandardized facial photographs were taken of North‐European participants from the RS (N=3,831; 58.2% female, median age 66.5) and the LLS (N=661; 50.5% female, median age 63.1). Facial wrinkles, pigmented spots and telangiectasia (RS only) were quantified either digitally (RS) or by two independent dermatologists (LLS). Perceived age was graded by an average of 27 (range:20‐30) and 60 (range:59‐61) assessors in the RS and LLS respectively. The associations between vitamin D and these phenotypes (all standardized using Z‐scores) were investigated using multivariable linear regression analyses, adjusted for chronological age, sex, self‐reported UV‐exposure, season, smoking, body mass index and skin color, followed by meta‐analysis of the two cohorts.ResultsHigher circulating 25‐hydroxyvitamin D was associated with more wrinkles (P‐value0.05). Self‐reported UV‐exposure was associated with all four phenotypes. In RS, a light skin color was associated with more pigmented spots (P‐value

Published
2016

49. Validated inference of smoking habits from blood with a finite DNA methylation marker set

Author

BIOS Consortium, Maas, Silvana C. E., Vidaki, Athina, Wilson, Rory, Teumer, Alexander, Liu, Fan, van Meurs, Joyce B. J., Uitterlinden, André G., Boomsma, Dorret I., de Geus, Eco J. C., Willemsen, Gonneke, van Dongen, Jenny, van der Kallen, Carla J. H., Slagboom, P. Eline, Beekman, Marian, van Heemst, Diana, van den Berg, Leonard H., Duijts, Liesbeth, Jaddoe, Vincent W. V., Ladwig, Karl-Heinz, Kunze, Sonja, Peters, Annette, Ikram, M. Arfan, Grabe, Hans J., Felix, Janine F., Waldenberger, Melanie, Franco, Oscar H., Ghanbari, Mohsen, and Kayser, Manfred

Published
2019

50. Validating biomarkers and models for epigenetic inference of alcohol consumption from blood

Author

Maas, Silvana C. E., Vidaki, Athina, Teumer, Alexander, Costeira, Ricardo, Wilson, Rory, van Dongen, Jenny, Beekman, Marian, Völker, Uwe, Grabe, Hans J., Kunze, Sonja, Ladwig, Karl-Heinz, van Meurs, Joyce B. J., Uitterlinden, André G., Voortman, Trudy, Boomsma, Dorret I., Slagboom, P. Eline, van Heemst, Diana, van der Kallen, Carla J. H., van den Berg, Leonard H., Waldenberger, Melanie, Völzke, Henry, Peters, Annette, Bell, Jordana T., Ikram, M. Arfan, Ghanbari, Mohsen, and Kayser, Manfred

Published
2021
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