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1. Genetic insights into resting heart rate and its role in cardiovascular disease

Author

van de Vegte, Yordi J., Eppinga, Ruben N., van der Ende, M. Yldau, Hagemeijer, Yanick P., Mahendran, Yuvaraj, Salfati, Elias, Smith, Albert V., Tan, Vanessa Y., Arking, Dan E., Ntalla, Ioanna, Appel, Emil V., Schurmann, Claudia, Brody, Jennifer A., Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing Hua, Isaacs, Aaron, Wang, Lihua, Luan, Jian’an, Hwang, Shih-Jen, Mononen, Nina, Auro, Kirsi, Jackson, Anne U., Bielak, Lawrence F., Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Müller-Nurasyid, Martina, Roselli, Carolina, Zhang, Weihua, Kleber, Marcus E., Guo, Xiuqing, Lin, Henry J., Pavani, Francesca, Galesloot, Tessel E., Noordam, Raymond, Milaneschi, Yuri, Schraut, Katharina E., den Hoed, Marcel, Degenhardt, Frauke, Trompet, Stella, van den Berg, Marten E., Pistis, Giorgio, Tham, Yih-Chung, Weiss, Stefan, Sim, Xueling S., Li, Hengtong L., van der Most, Peter J., Nolte, Ilja M., Lyytikäinen, Leo-Pekka, Said, M. Abdullah, Witte, Daniel R., Iribarren, Carlos, Launer, Lenore, Ring, Susan M., de Vries, Paul S., Sever, Peter, Linneberg, Allan, Bottinger, Erwin P., Padmanabhan, Sandosh, Psaty, Bruce M., Sotoodehnia, Nona, Kolcic, Ivana, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Balkau, Beverley, Silva, Claudia T., Newton-Cheh, Christopher H., Nikus, Kjell, Salo, Perttu, Mohlke, Karen L., Peyser, Patricia A., Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari, Rao, Dabeeru C., Cornelis, Marilyn C., Faul, Jessica D., Smith, Jennifer A., Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria Pina, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie, Sinner, Moritz F., Strauch, Konstantin, Delgado, Graciela E., Taylor, Kent D., Yao, Jie, Foco, Luisa, Melander, Olle, de Graaf, Jacqueline, de Mutsert, Renée, de Geus, Eco J. C., Johansson, Åsa, Joshi, Peter K., Lind, Lars, Franke, Andre, Macfarlane, Peter W., Tarasov, Kirill V., Tan, Nicholas, Felix, Stephan B., Tai, E-Shyong, Quek, Debra Q., Snieder, Harold, Ormel, Johan, Ingelsson, Martin, Lindgren, Cecilia, Morris, Andrew P., Raitakari, Olli T., Hansen, Torben, Assimes, Themistocles, Gudnason, Vilmundur, Timpson, Nicholas J., Morrison, Alanna C., Munroe, Patricia B., Strachan, David P., Grarup, Niels, Loos, Ruth J. F., Heckbert, Susan R., Vollenweider, Peter, Hayward, Caroline, Stefansson, Kari, Froguel, Philippe, Groop, Leif, Wareham, Nicholas J., van Duijn, Cornelia M., Feitosa, Mary F., O’Donnell, Christopher J., Kähönen, Mika, Perola, Markus, Boehnke, Michael, Kardia, Sharon L. R., Erdmann, Jeanette, Palmer, Colin N. A., Ohlsson, Claes, Porteous, David J., Eriksson, Johan G., Bouchard, Claude, Moebus, Susanne, Kraft, Peter, Weir, David R., Cusi, Daniele, Ferrucci, Luigi, Ulivi, Sheila, Girotto, Giorgia, Correa, Adolfo, Kääb, Stefan, Peters, Annette, Chambers, John C., Kooner, Jaspal S., März, Winfried, Rotter, Jerome I., Hicks, Andrew A., Smith, J. Gustav, Kiemeney, Lambertus A. L. M., Mook-Kanamori, Dennis O., Penninx, Brenda W. J. H., Gyllensten, Ulf, Wilson, James F., Burgess, Stephen, Sundström, Johan, Lieb, Wolfgang, Jukema, J. Wouter, Eijgelsheim, Mark, Lakatta, Edward L. M., Cheng, Ching-Yu, Dörr, Marcus, Wong, Tien-Yin, Sabanayagam, Charumathi, Oldehinkel, Albertine J., Riese, Harriette, Lehtimäki, Terho, Verweij, Niek, and van der Harst, Pim

Published
2023
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3. Commentary on "The Challenge of Transforming the Diagnostic System of Personality Disorders".

Author

Hopwood, Christopher J, Krueger, Robert F, Watson, David, Widiger, Thomas A, Althoff, Robert R, Ansell, Emily B, Bach, Bo, Bagby, R Michael, Blais, Mark A, Bornovalova, Marina A, Chmielewski, Michael, Cicero, David C, Conway, Christopher, De Clerq, Barbara, De Fruyt, Filip, Docherty, Anna R, Eaton, Nicholas R, Edens, John F, Forbes, Miriam K, Forbush, Kelsie T, Hengartner, Michael P, Ivanova, Masha Y, Leising, Daniel, Lukowitsky, Mark R, Lynam, Donald R, Markon, Kristian E, Miller, Joshua D, Morey, Leslie C, Mullins-Sweatt, Stephanie N, Ormel, Johan, Patrick, Christopher J, Pincus, Aaron L, Ruggero, Camilo, Samuel, Douglas B, Sellbom, Martin, Tackett, Jennifer L, Thomas, Katherine M, Trull, Timothy J, Vachon, David D, Waldman, Irwin D, Waszczuk, Monika A, Waugh, Mark H, Wright, Aidan GC, Yalch, Mathew M, Zald, David H, and Zimmermann, Johannes

Subjects
Psychology, Clinical and Health Psychology, Social and Personality Psychology, Applied and Developmental Psychology, Psychiatry, Applied and developmental psychology, Clinical and health psychology, Social and personality psychology
Published
2020

4. Redefining Phenotypes to Advance Psychiatric Genetics: Implications From Hierarchical Taxonomy of Psychopathology

Author

Waszczuk, Monika A, Eaton, Nicholas R, Krueger, Robert F, Shackman, Alexander J, Waldman, Irwin D, Zald, David H, Lahey, Benjamin B, Patrick, Christopher J, Conway, Christopher C, Ormel, Johan, Hyman, Steven E, Fried, Eiko I, Forbes, Miriam K, Docherty, Anna R, Althoff, Robert R, Bach, Bo, Chmielewski, Michael, DeYoung, Colin G, Forbush, Kelsie T, Hallquist, Michael, Hopwood, Christopher J, Ivanova, Masha Y, Jonas, Katherine G, Latzman, Robert D, Markon, Kristian E, Mullins-Sweatt, Stephanie N, Pincus, Aaron L, Reininghaus, Ulrich, South, Susan C, Tackett, Jennifer L, Watson, David, Wright, Aidan GC, and Kotov, Roman

Subjects
Biotechnology, Genetics, Human Genome, Brain Disorders, Mental Health, Genetic Testing, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Humans, Mental Disorders, Phenotype, Psychiatry, Psychology, Clinical, behavior genetics, comorbidity, general factor, molecular genetics, nosology
Abstract

Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorders, and to studying psychiatric etiology, than current diagnostic categories. Specifically, genes are expected to operate at different levels of the HiTOP hierarchy, with some highly pleiotropic genes influencing higher order psychopathology (e.g., the general factor), whereas other genes conferring more specific risk for individual spectra (e.g., internalizing), subfactors (e.g., fear disorders), or narrow symptoms (e.g., mood instability). We propose that the HiTOP model aligns well with the current understanding of the higher order genetic structure of psychopathology that has emerged from a large body of family and twin studies. We also discuss the convergence between the HiTOP model and findings from recent molecular studies of psychopathology indicating broad genetic pleiotropy, such as cross-disorder SNP-based shared genetic covariance and polygenic risk scores, and we highlight molecular genetic studies that have successfully redefined phenotypes to enhance precision and statistical power. Finally, we suggest how to integrate a HiTOP approach into future molecular genetic research, including quantitative and hierarchical assessment tools for future data-collection and recommendations concerning phenotypic analyses. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Published
2020

5. Commentary on "The Challenge of Transforming the Diagnostic System of Personality Disorders".

Author

Hopwood, Christopher J, Krueger, Robert F, Watson, David, Widiger, Thomas A, Althoff, Robert R, Ansell, Emily B, Bach, Bo, Bagby, R Michael, Blais, Mark A, Bornovalova, Marina A, Chmielewski, Michael, Cicero, David C, Conway, Christopher, De Clerq, Barbara, De Fruyt, Filip, Docherty, Anna R, Eaton, Nicholas R, Edens, John F, Forbes, Miriam K, Forbush, Kelsie T, Hengartner, Michael P, Ivanova, Masha Y, Leising, Daniel, Lukowitsky, Mark R, Lynam, Donald R, Markon, Kristian E, Miller, Joshua D, Morey, Leslie C, Mullins-Sweatt, Stephanie N, Ormel, Johan, Patrick, Christopher J, Pincus, Aaron L, Ruggero, Camilo, Samuel, Douglas B, Sellbom, Martin, Tackett, Jennifer L, Thomas, Katherine M, Trull, Timothy J, Vachon, David D, Waldman, Irwin D, Waszczuk, Monika A, Waugh, Mark H, Wright, Aidan GC, Yalch, Mathew M, Zald, David H, and Zimmermann, Johannes

Subjects
Psychology, Psychiatry
Published
2019

8. Erratum: Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Author

Nolte, Ilja, Munoz, M, Tragante, Vinicius, Amare, Azmeraw, Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy, Bis, Joshua, Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen, Kluttig, Alexander, Krijthe, Bouwe, Kumar, Jitender, van der Laan, Sander, Lyytikäinen, Leo-Pekka, Maihofer, Adam, Minassian, Arpi, van der Most, Peter, Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James, Thayer, Julian, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen, de Bakker, Paul, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie, Christophersen, Ingrid, Dietrich, Andrea, Ehret, George, Ellinor, Patrick, Eskola, Markku, Felix, Janine, Floras, John, Franco, Oscar, Friberg, Peter, Gademan, Maaike, Geyer, Mark, Giedraitis, Vilmantas, Hartman, Catharina, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti, Kors, Jan, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy, Lefrandt, Joop, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian, Lin, Henry, Lindgren, Cecilia, Lubitz, Steven, Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew, Nalls, Mike, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari, OConnor, Daniel, Ormel, Johan, Perz, Siegfried, Peters, Annette, and Psaty, Bruce

Abstract

This corrects the article DOI: 10.1038/ncomms15805.

Published
2017

9. Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Author

Nolte, Ilja M, Munoz, M Loretto, Tragante, Vinicius, Amare, Azmeraw T, Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L, Bis, Joshua C, Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P, Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X, Minassian, Arpi, van der Most, Peter J, Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D, Thayer, Julian F, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G, de Bakker, Paul IW, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R, Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F, Floras, John S, Franco, Oscar H, Friberg, Peter, Gademan, Maaike GJ, Geyer, Mark A, Giedraitis, Vilmantas, Hartman, Catharina A, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M, Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C, Lefrandt, Joop D, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C, Lin, Henry J, Lindgren, Cecilia M, Lubitz, Steven A, Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P, Nalls, Mike A, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E, O'Connor, Daniel T, Ormel, Johan, Perz, Siegfried, Peters, Annette, and Psaty, Bruce M

Subjects
Humans, Heart Diseases, Genetic Predisposition to Disease, RGS Proteins, Potassium Channels, Muscle Proteins, Risk Factors, Cohort Studies, Blood Pressure, Heart Rate, Polymorphism, Single Nucleotide, Quantitative Trait Loci, European Continental Ancestry Group, Genome-Wide Association Study, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Cardiovascular, Genetics, Heart Disease
Abstract

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74g

Published
2017

10. Les progrès dans la réalisation de la classification quantitative de la psychopathologie

Author

Krueger, Robert F., Kotov, Roman, Watson, David, Forbes, Miriam K., Eaton, Nicholas R., Ruggero, Camilo J., Simms, Leonard J., Widiger, Thomas A., Achenbach, Thomas M., Bach, Bo, Bagby, R. Michael, Bornovalova, Marina A., Carpenter, William T., Chmielewski, Michael, Cicero, David C., Clark, Lee Anna, Conway, Christopher, DeClercq, Barbara, DeYoung, Colin G., Docherty, Anna R., Drislane, Laura E., First, Michael B., Forbush, Kelsie T., Hallquist, Michael, Haltigan, John D., Hopwood, Christopher J., Ivanova, Masha Y., Jonas, Katherine G., Latzman, Robert D., Markon, Kristian E., Miller, Joshua D., Morey, Leslie C., Mullins-Sweatt, Stephanie N., Ormel, Johan, Patalay, Praveetha, Patrick, Christopher J., Pincus, Aaron L., Regier, Darrel A., Reininghaus, Ulrich, Rescorla, Leslie A., Samuel, Douglas B., Sellbom, Martin, Shackman, Alexander J., Skodol, Andrew, Slade, Tim, South, Susan C., Sunderland, Matthew, Tackett, Jennifer L., Venables, Noah C., Waldman, Irwin D., Waszczuk, Monika A., Waugh, Mark H., Wright, Aidan G.C., Zald, David H., and Zimmermann, Johannes

Published
2021
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12. Continuity of Psychopathology Throughout Adolescence and Young Adulthood.

Author

Richards, Jennifer S., Hartman, Catharina A., Ormel, Johan, and Oldehinkel, Albertine J.

Subjects
YOUNG adults, INTERNALIZING behavior, MENTAL illness, DUTCH people, PATHOLOGICAL psychology
Abstract

This study tested two opposing hypotheses on the continuity of psychopathology throughout adolescence and young adulthood; differentiation versus dynamic mutualism. Differentiation predicts that co-occurrence decreases, while dynamic mutualism predicts that co-occurrence increases due to causal interactions amongst mental health problems. Using data from the Dutch TRacking Adolescents' Individual Lives Survey (n = 2228, 51% female), we studied the development of self-reported internalizing, externalizing, and attention problems at ages 11 to 26 across six waves. Random-intercept cross-lagged panel modeling was employed to distinguish within-person development from stable between-person processes. Large stable between-person associations indicated that adolescents with internalizing problems tended to have both externalizing and attention problems as well. On a within-person level, mental health problems showed partial stability and strong cross-sectional co-occurrence. Within-wave associations of internalizing with externalizing or attention problems decreased between age 11 and 16 years, after which they increased again. Little heterotypic continuity was found: age 11 externalizing predicted age 13 attention, which in turn predicted age 16 externalizing problems, and internalizing predicted externalizing problems across ages 22 to 26. Findings were similar for males and females. Our findings suggest co-occurrence decreases during early and middle adolescence, supporting differentiation. While co-occurrence increased again into young adulthood, this could not be labeled as dynamic mutualism because little evidence for heterotypic continuity was found in this phase of life. The strong stable links between internalizing, externalizing, and attention problems stress the importance of targeting these mental health problems and their shared risk factors together. [ABSTRACT FROM AUTHOR]

Published
2024
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13. A normal-probit-binomial model for the analysis of repeated sum scores from multi-item questionnaires.

Author

Nooraee, Nazanin, Molenberghs, Geert, Ormel, Johan, and van den Heuvel, Edwin R.

Subjects
PROBIT analysis, REGRESSION analysis, STATISTICAL correlation, ITEM response theory, MODEL theory, QUESTIONNAIRES
Abstract

Sum scores from questionnaire data are frequently analyzed under the normality assumption which is not always tenable due to for instance the skewness of the distribution, or the discreteness of the sum scores for small number of items. Alternatively, an ordinal regression analysis can be applied, but this approach seems appropriate only for very small number of items. The current state-of-the-art approach is to apply a beta-binomial model, though the beta-binomial model does not simply connect to item-response theory models that may describe the underlying items of the questionnaire, and it is more cumbersome to fit to multi domain sum scores or repeated longitudinal single sum scores. This paper proposes a normal-probit-binomial model for repeated sum scores that has an item level interpretation under certain assumptions without having to analyze the individual items. All parameters, the temporal correlation coefficients, and the mean difficulty parameter were almost unbiasedly estimated, irrespective of the set of item difficulty parameters. The coverage probability of the 95% confidence intervals were close to the nominal level, except for the correlation coefficients that were slightly liberal. Our model performed slightly better than the beta-binomial model on cross-sectional data and it handles missing items easily. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia

Author

Simino, Jeannette, Shi, Gang, Bis, Joshua C, Chasman, Daniel I, Ehret, Georg B, Gu, Xiangjun, Guo, Xiuqing, Hwang, Shih-Jen, Sijbrands, Eric, Smith, Albert V, Verwoert, Germaine C, Bragg-Gresham, Jennifer L, Cadby, Gemma, Chen, Peng, Cheng, Ching-Yu, Corre, Tanguy, de Boer, Rudolf A, Goel, Anuj, Johnson, Toby, Khor, Chiea-Chuen, Study, LifeLines Cohort, Alizadeh, Behrooz Z, Boezen, H Marike, Bruinenberg, Marcel, Franke, Lude, van der Harst, Pim, Hillege, Hans L, van der Klauw, Melanie M, Navis, Gerjan, Ormel, Johan, Postma, Dirkje S, Rosmalen, Judith GM, Slaets, Joris P, Snieder, Harold, Stolk, Ronald P, Wolffenbuttel, Bruce HR, Wijmenga, Cisca, Lluís-Ganella, Carla, Luan, Jian’an, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Sim, Xueling, Sõber, Siim, van der Most, Peter J, Verweij, Niek, Zhao, Jing Hua, Amin, Najaf, Boerwinkle, Eric, Bouchard, Claude, Dehghan, Abbas, Eiriksdottir, Gudny, Elosua, Roberto, Franco, Oscar H, Gieger, Christian, Harris, Tamara B, Hercberg, Serge, Hofman, Albert, James, Alan L, Johnson, Andrew D, Kähönen, Mika, Khaw, Kay-Tee, Kutalik, Zoltan, Larson, Martin G, Launer, Lenore J, Li, Guo, Liu, Jianjun, Liu, Kiang, Morrison, Alanna C, Ong, Rick Twee-Hee, Papanicolau, George J, Penninx, Brenda W, Psaty, Bruce M, Raffel, Leslie J, Raitakari, Olli T, Rice, Kenneth, Rivadeneira, Fernando, Rose, Lynda M, Sanna, Serena, Scott, Robert A, Siscovick, David S, Uitterlinden, Andre G, Vaidya, Dhananjay, Vasan, Ramachandran S, Vithana, Eranga Nishanthie, Völker, Uwe, Völzke, Henry, Watkins, Hugh, Young, Terri L, Aung, Tin, Bochud, Murielle, Farrall, Martin, Hartman, Catharina A, Laan, Maris, Lakatta, Edward G, Lehtimäki, Terho, and Loos, Ruth JF

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Clinical Research, Human Genome, Aging, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Age Factors, Aged, Blood Pressure, Cohort Studies, Humans, Middle Aged, Young Adult, LifeLines Cohort Study, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10(-8)) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10(-4)) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.

Published
2014

17. Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised controlled trial

Author

Bockting, Claudi L H, Klein, Nicola S, Elgersma, Hermien J, van Rijsbergen, Gerard D, Slofstra, Christien, Ormel, Johan, Buskens, Erik, Dekker, Jack, de Jong, Peter J, Nolen, Willem A, Schene, Aart H, Hollon, Steven D, and Burger, Huibert

Published
2018
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28. Genetic insights into resting heart rate and its role in cardiovascular disease

Author

van de Vegte, Yordi, Eppinga, Ruben P., van der Ende, M. Yldau, Hagemeijer, Yanick, Mahendran, Yuvaraj V., Salfati, Elias Y., Smith, Albert E., Tan, Vanessa, Arking, Dan V., Ntalla, Ioanna, Appel, Emil A., Schurmann, Claudia, Brody, Jennifer, Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing Hua, Isaacs, Aaron, Wang, Lihua, Luan, Jian'an, Hwang, Shih-Jen, Mononen, Nina U., Auro, Kirsi F., Jackson, Anne, Bielak, Lawrence, Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Mueller-Nurasyid, Martina, Roselli, Carolina E., Zhang, Weihua, Kleber, Marcus J., Guo, Xiuqing, Lin, Henry E., Pavani, Francesca, Galesloot, Tessel, Noordam, Raymond E., Milaneschi, Yuri, Schraut, Katharina, den Hoed, Marcel, Degenhardt, Frauke E., Trompet, Stella, van den Berg, Marten, Pistis, Giorgio, Tham, Yih-Chung S., Weiss, Stefan L., Sim, Xueling J., Li, Hengtong M., van der Most, Peter, Nolte, Ilja, Lyytikaeinen, Leo-Pekka R., Said, M. Abdullah, Witte, Daniel, Iribarren, Carlos M., Launer, Lenore S., Ring, Susan, de Vries, Paul, Sever, Peter P., Linneberg, Allan, Bottinger, Erwin M., Padmanabhan, Sandosh, Psaty, Bruce, Sotoodehnia, Nona, Kolcic, Ivana, Roshandel, Delnaz D., Paterson, Andrew O., Arnar, David F., Gudbjartsson, Daniel, Holm, Hilma, Balkau, Beverley T., Silva, Claudia H., Newton-Cheh, Christopher, Nikus, Kjell, Salo, Perttu L., Mohlke, Karen A., Peyser, Patricia, Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari C., Rao, Dabeeru C., Cornelis, Marilyn D., Faul, Jessica A., Smith, Jennifer, Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria Pina, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie F., Sinner, Moritz, Strauch, Konstantin E., Delgado, Graciela D., Taylor, Kent, Yao, Jie, Foco, Luisa, Melander, Olle, de Graaf, Jacqueline, de Mutsert, Renee, de Geus, Eco J. C., Johansson, Åsa, Joshi, Peter K., Lind, Lars, Franke, Andre W., Macfarlane, Peter V., Tarasov, Kirill, Tan, Nicholas B., Felix, Stephan, Tai, E-Shyong Q., Quek, Debra, Snieder, Harold, Ormel, Johan, Ingelsson, Martin, Lindgren, Cecilia P., Morris, Andrew T., Raitakari, Olli, Hansen, Torben, Assimes, Themistocles, Gudnason, Vilmundur J., Timpson, Nicholas C., Morrison, Alanna B., Munroe, Patricia P., Strachan, David, Grarup, Niels, Loos, Ruth J. F. R., Heckbert, Susan, Vollenweider, Peter, Hayward, Caroline, Stefansson, Kari, Froguel, Philippe, Groop, Leif J., Wareham, Nicholas M., van Duijn, Cornelia F., Feitosa, Mary J., O'Donnell, Christopher, Kaehoenen, Mika, Perola, Markus, Boehnke, Michael, Kardia, Sharon L. R., Erdmann, Jeanette, Palmer, Colin N. A., Ohlsson, Claes J., Porteous, David G., Eriksson, Johan, Bouchard, Claude, Moebus, Susanne, Kraft, Peter R., Weir, David, Cusi, Daniele, Ferrucci, Luigi, Ulivi, Sheila, Girotto, Giorgia, Correa, Adolfo, Kaeaeb, Stefan, Peters, Annette C., Chambers, John S., Kooner, Jaspal, Maerz, Winfried I., Rotter, Jerome A., Hicks, Andrew, Smith, J. Gustav, Kiemeney, Lambertus A. L. M. O., Mook-Kanamori, Dennis, Penninx, Brenda W. J. H., Gyllensten, Ulf, Wilson, James, Burgess, Stephen, Sundström, Johan, Lieb, Wolfgang, Jukema, J. Wouter, Eijgelsheim, Mark, Lakatta, Edward L. M., Cheng, Ching-Yu, Doerr, Marcus, Wong, Tien-Yin, Sabanayagam, Charumathi J., Oldehinkel, Albertine, Riese, Harriette, Lehtimaeki, Terho, Verweij, Niek, van der Harst, Pim, van de Vegte, Yordi, Eppinga, Ruben P., van der Ende, M. Yldau, Hagemeijer, Yanick, Mahendran, Yuvaraj V., Salfati, Elias Y., Smith, Albert E., Tan, Vanessa, Arking, Dan V., Ntalla, Ioanna, Appel, Emil A., Schurmann, Claudia, Brody, Jennifer, Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing Hua, Isaacs, Aaron, Wang, Lihua, Luan, Jian'an, Hwang, Shih-Jen, Mononen, Nina U., Auro, Kirsi F., Jackson, Anne, Bielak, Lawrence, Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Mueller-Nurasyid, Martina, Roselli, Carolina E., Zhang, Weihua, Kleber, Marcus J., Guo, Xiuqing, Lin, Henry E., Pavani, Francesca, Galesloot, Tessel, Noordam, Raymond E., Milaneschi, Yuri, Schraut, Katharina, den Hoed, Marcel, Degenhardt, Frauke E., Trompet, Stella, van den Berg, Marten, Pistis, Giorgio, Tham, Yih-Chung S., Weiss, Stefan L., Sim, Xueling J., Li, Hengtong M., van der Most, Peter, Nolte, Ilja, Lyytikaeinen, Leo-Pekka R., Said, M. Abdullah, Witte, Daniel, Iribarren, Carlos M., Launer, Lenore S., Ring, Susan, de Vries, Paul, Sever, Peter P., Linneberg, Allan, Bottinger, Erwin M., Padmanabhan, Sandosh, Psaty, Bruce, Sotoodehnia, Nona, Kolcic, Ivana, Roshandel, Delnaz D., Paterson, Andrew O., Arnar, David F., Gudbjartsson, Daniel, Holm, Hilma, Balkau, Beverley T., Silva, Claudia H., Newton-Cheh, Christopher, Nikus, Kjell, Salo, Perttu L., Mohlke, Karen A., Peyser, Patricia, Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari C., Rao, Dabeeru C., Cornelis, Marilyn D., Faul, Jessica A., Smith, Jennifer, Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria Pina, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie F., Sinner, Moritz, Strauch, Konstantin E., Delgado, Graciela D., Taylor, Kent, Yao, Jie, Foco, Luisa, Melander, Olle, de Graaf, Jacqueline, de Mutsert, Renee, de Geus, Eco J. C., Johansson, Åsa, Joshi, Peter K., Lind, Lars, Franke, Andre W., Macfarlane, Peter V., Tarasov, Kirill, Tan, Nicholas B., Felix, Stephan, Tai, E-Shyong Q., Quek, Debra, Snieder, Harold, Ormel, Johan, Ingelsson, Martin, Lindgren, Cecilia P., Morris, Andrew T., Raitakari, Olli, Hansen, Torben, Assimes, Themistocles, Gudnason, Vilmundur J., Timpson, Nicholas C., Morrison, Alanna B., Munroe, Patricia P., Strachan, David, Grarup, Niels, Loos, Ruth J. F. R., Heckbert, Susan, Vollenweider, Peter, Hayward, Caroline, Stefansson, Kari, Froguel, Philippe, Groop, Leif J., Wareham, Nicholas M., van Duijn, Cornelia F., Feitosa, Mary J., O'Donnell, Christopher, Kaehoenen, Mika, Perola, Markus, Boehnke, Michael, Kardia, Sharon L. R., Erdmann, Jeanette, Palmer, Colin N. A., Ohlsson, Claes J., Porteous, David G., Eriksson, Johan, Bouchard, Claude, Moebus, Susanne, Kraft, Peter R., Weir, David, Cusi, Daniele, Ferrucci, Luigi, Ulivi, Sheila, Girotto, Giorgia, Correa, Adolfo, Kaeaeb, Stefan, Peters, Annette C., Chambers, John S., Kooner, Jaspal, Maerz, Winfried I., Rotter, Jerome A., Hicks, Andrew, Smith, J. Gustav, Kiemeney, Lambertus A. L. M. O., Mook-Kanamori, Dennis, Penninx, Brenda W. J. H., Gyllensten, Ulf, Wilson, James, Burgess, Stephen, Sundström, Johan, Lieb, Wolfgang, Jukema, J. Wouter, Eijgelsheim, Mark, Lakatta, Edward L. M., Cheng, Ching-Yu, Doerr, Marcus, Wong, Tien-Yin, Sabanayagam, Charumathi J., Oldehinkel, Albertine, Riese, Harriette, Lehtimaeki, Terho, Verweij, Niek, and van der Harst, Pim

Abstract

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Published
2023
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29. A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts

Author

Middeldorp, Christel M., Hammerschlag, Anke R., Ouwens, Klaasjan G., Groen-Blokhuis, Maria M., St. Pourcain, Beate, Greven, Corina U., Pappa, Irene, Tiesler, Carla M.T., Ang, Wei, Nolte, Ilja M., Vilor-Tejedor, Natalia, Bacelis, Jonas, Ebejer, Jane L., Zhao, Huiying, Davies, Gareth E., Ehli, Erik A., Evans, David M., Fedko, Iryna O., Guxens, Mònica, Hottenga, Jouke-Jan, Hudziak, James J., Jugessur, Astanand, Kemp, John P., Krapohl, Eva, Martin, Nicholas G., Murcia, Mario, Myhre, Ronny, Ormel, Johan, Ring, Susan M., Standl, Marie, Stergiakouli, Evie, Stoltenberg, Camilla, Thiering, Elisabeth, Timpson, Nicholas J., Trzaskowski, Maciej, van der Most, Peter J., Wang, Carol, Nyholt, Dale R., Medland, Sarah E., Neale, Benjamin, Jacobsson, Bo, Sunyer, Jordi, Hartman, Catharina A., Whitehouse, Andrew J.O., Pennell, Craig E., Heinrich, Joachim, Plomin, Robert, Davey Smith, George, Tiemeier, Henning, Posthuma, Danielle, and Boomsma, Dorret I.

Published
2016
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36. Adding mindfulness-based cognitive therapy to maintenance antidepressant medication for prevention of relapse/recurrence in major depressive disorder: Randomised controlled trial

Author

Huijbers, Marloes J., Spinhoven, Philip, Spijker, Jan, Ruhé, Henricus G., van Schaik, Digna J.F., van Oppen, Patricia, Nolen, Willem A., Ormel, Johan, Kuyken, Willem, van der Wilt, Gert Jan, Blom, Marc B.J., Schene, Aart H., Donders, A. Rogier T., and Speckens, Anne E.M.

Published
2015
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42. Longitudinal Associations between Depressive Problems, Academic Performance, and Social Functioning in Adolescent Boys and Girls

Author

Verboom, Charlotte E., Sijtsema, Jelle J., Verhulst, Frank C., Penninx, Brenda W. J. H., and Ormel, Johan

Abstract

Depressive problems and academic performance, social well-being, and social problems in adolescents are strongly associated. However, longitudinal and bidirectional relations between the two remain unclear, as well as the role of gender. Consequently, this study focuses on the relation between depressive problems and three types of functioning in adolescents while testing gender differences. Depressive problems and functioning of 2,230 children were measured with structured questionnaires. The measurements took place biennially over 3 waves, from late childhood into adolescence (age range = 10-18 years). To examine the longitudinal relation between depression and functioning, path analyses with cross-lagged effects were conducted with structural equation modeling. Multigroup analyses were used to test for gender differences, which were only observed for academic performance. Other findings indicated substantial stability in depressive problems and functioning over time and within-wave correlations between depression and the 3 types of functioning. Poor social well-being was predicted by depressive problems but not the other way around. The relation between depressive and social problems was bidirectional, that is, they predicted each other. Finally, depressive problems and academic performance were bidirectionally related as well but only in girls.

Published
2014
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48. List of Contributors

Author

Allemand, Mathias, primary, Back, Mitja D., additional, Bleidorn, Wiebke, additional, De Caluwé, Elien, additional, De Clercq, Barbara, additional, De Fruyt, Filip, additional, Edmonds, Grant W., additional, Finn, Christine, additional, Fraley, R. Chris, additional, Freund, Alexandra M., additional, Gerstorf, Denis, additional, Geukes, Katharina, additional, Hennecke, Marie, additional, Herzhoff, Kathrin, additional, Hill, Patrick L., additional, Hudson, Nathan W., additional, Hülür, Gizem, additional, Infurna, Charles J., additional, Infurna, Frank J., additional, Jackson, Joshua J., additional, Jeronimus, Bertus F., additional, Kandler, Christian, additional, Kim, Hyunji, additional, Klimstra, Theo A., additional, Kushner, Shauna C., additional, Luhmann, Maike, additional, McLean, Kate C., additional, Mehl, Matthias R., additional, Mõttus, René, additional, Mueller, Swantje, additional, Neyer, Franz J., additional, Nickel, Lauren B., additional, Ormel, Johan, additional, Orth, Ulrich, additional, Papendick, Michael, additional, Rauthmann, John F., additional, Reitz, Anne K., additional, Riese, Harriëtte, additional, Roberts, Brent W., additional, Sasaki, Joni Y., additional, Schmiedek, Florian, additional, Schultz, Leah H., additional, Schwaba, Ted, additional, Smith, Conor G., additional, Specht, Jule, additional, Staudinger, Ursula M., additional, Stoll, Gundula, additional, Tackett, Jennifer L., additional, Trautwein, Ulrich, additional, van Doeselaar, Lotte, additional, van Zalk, Maarten H.W., additional, Verbeke, Lize, additional, Voelkle, Manuel C., additional, VonKorff, Michael, additional, Wagner, Jenny, additional, Weiss, Alexander, additional, Weston, Sara J., additional, Zapko-Willmes, Alexandra, additional, and Zimmermann, Julia, additional

Published
2017
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