TY - JOUR A1 - Tian, Mei A1 - Reichetzeder, Christoph A1 - Li, Jian A1 - Hocher, Berthold T1 - Low birth weight, a risk factor for diseases in later life, is a surrogate of insulin resistance at birth JF - Journal of hypertension N2 - Low birth weight (LBW) is associated with diseases in adulthood. The birthweight attributed risk is independent of confounding such as gestational age, sex of the newborn but also social factors. The birthweight attributed risk for diseases in later life holds for the whole spectrum of birthweight. This raises the question what pathophysiological principle is actually behind the association. In this review, we provide evidence that LBW is a surrogate of insulin resistance. Insulin resistance has been identified as a key factor leading to type 2 diabetes, cardiovascular disease as well as kidney diseases. We first provide evidence linking LBW to insulin resistance during intrauterine life. This might be caused by both genetic (genetic variations of genes controlling glucose homeostasis) and/or environmental factors (due to alterations of macronutrition and micronutrition of the mother during pregnancy, but also effects of paternal nutrition prior to conception) leading via epigenetic modifications to early life insulin resistance and alterations of intrauterine growth, as insulin is a growth factor in early life. LBW is rather a surrogate of insulin resistance in early life - either due to inborn genetic or environmental reasons - rather than a player on its own. KW - epigenetics KW - fetal programing KW - genetics KW - insulin resistance KW - low birth weight Y1 - 2019 U6 - https://doi.org/10.1097/HJH.0000000000002156 SN - 0263-6352 SN - 1473-5598 VL - 37 IS - 11 SP - 2123 EP - 2134 PB - Kluwer CY - Philadelphia ER - TY - JOUR A1 - Warrington, Nicole A1 - Beaumont, Robin A1 - Horikoshi, Momoko A1 - Day, Felix R. A1 - Helgeland, Øyvind A1 - Laurin, Charles A1 - Bacelis, Jonas A1 - Peng, Shouneng A1 - Hao, Ke A1 - Feenstra, Bjarke A1 - Wood, Andrew R. A1 - Mahajan, Anubha A1 - Tyrrell, Jessica A1 - Robertson, Neil R. A1 - Rayner, N. William A1 - Qiao, Zhen A1 - Moen, Gunn-Helen A1 - Vaudel, Marc A1 - Marsit, Carmen A1 - Chen, Jia A1 - Nodzenski, Michael A1 - Schnurr, Theresia M. A1 - Zafarmand, Mohammad Hadi A1 - Bradfield, Jonathan P. A1 - Grarup, Niels A1 - Kooijman, Marjolein N. A1 - Li-Gao, Ruifang A1 - Geller, Frank A1 - Ahluwalia, Tarunveer Singh A1 - Paternoster, Lavinia A1 - Rueedi, Rico A1 - Huikari, Ville A1 - Hottenga, Jouke-Jan A1 - Lyytikäinen, Leo-Pekka A1 - Cavadino, Alana A1 - Metrustry, Sarah A1 - Cousminer, Diana L. A1 - Wu, Ying A1 - Thiering, Elisabeth Paula A1 - Wang, Carol A. A1 - Have, Christian Theil A1 - Vilor-Tejedor, Natalia A1 - Joshi, Peter K. A1 - Painter, Jodie N. A1 - Ntalla, Ioanna A1 - Myhre, Ronny A1 - Pitkänen, Niina A1 - van Leeuwen, Elisabeth M. A1 - Joro, Raimo A1 - Lagou, Vasiliki A1 - Richmond, Rebecca C. A1 - Espinosa, Ana A1 - Barton, Sheila J. A1 - Inskip, Hazel M. A1 - Holloway, John W. A1 - Santa-Marina, Loreto A1 - Estivill, Xavier A1 - Ang, Wei A1 - Marsh, Julie A. A1 - Reichetzeder, Christoph A1 - Marullo, Letizia A1 - Hocher, Berthold A1 - Lunetta, Kathryn L. A1 - Murabito, Joanne M. A1 - Relton, Caroline L. A1 - Kogevinas, Manolis A1 - Chatzi, Leda A1 - Allard, Catherine A1 - Bouchard, Luigi A1 - Hivert, Marie-France A1 - Zhang, Ge A1 - Muglia, Louis J. A1 - Heikkinen, Jani A1 - Morgen, Camilla S. A1 - van Kampen, Antoine H. C. A1 - van Schaik, Barbera D. C. A1 - Mentch, Frank D. A1 - Langenberg, Claudia A1 - Scott, Robert A. A1 - Zhao, Jing Hua A1 - Hemani, Gibran A1 - Ring, Susan M. A1 - Bennett, Amanda J. A1 - Gaulton, Kyle J. A1 - Fernandez-Tajes, Juan A1 - van Zuydam, Natalie R. A1 - Medina-Gomez, Carolina A1 - de Haan, Hugoline G. A1 - Rosendaal, Frits R. A1 - Kutalik, Zoltán A1 - Marques-Vidal, Pedro A1 - Das, Shikta A1 - Willemsen, Gonneke A1 - Mbarek, Hamdi A1 - Müller-Nurasyid, Martina A1 - Standl, Marie A1 - Appel, Emil V. R. A1 - Fonvig, Cilius Esmann A1 - Trier, Caecilie A1 - van Beijsterveldt, Catharina E. M. A1 - Murcia, Mario A1 - Bustamante, Mariona A1 - Bonàs-Guarch, Sílvia A1 - Hougaard, David M. A1 - Mercader, Josep M. A1 - Linneberg, Allan A1 - Schraut, Katharina E. A1 - Lind, Penelope A. A1 - Medland, Sarah Elizabeth A1 - Shields, Beverley M. A1 - Knight, Bridget A. A1 - Chai, Jin-Fang A1 - Panoutsopoulou, Kalliope A1 - Bartels, Meike A1 - Sánchez, Friman A1 - Stokholm, Jakob A1 - Torrents, David A1 - Vinding, Rebecca K. A1 - Willems, Sara M. A1 - Atalay, Mustafa A1 - Chawes, Bo L. A1 - Kovacs, Peter A1 - Prokopenko, Inga A1 - Tuke, Marcus A. A1 - Yaghootkar, Hanieh A1 - Ruth, Katherine S. A1 - Jones, Samuel E. A1 - Loh, Po-Ru A1 - Murray, Anna A1 - Weedon, Michael N. A1 - Tönjes, Anke A1 - Stumvoll, Michael A1 - Michaelsen, Kim Fleischer A1 - Eloranta, Aino-Maija A1 - Lakka, Timo A. A1 - van Duijn, Cornelia M. A1 - Kiess, Wieland A1 - Koerner, Antje A1 - Niinikoski, Harri A1 - Pahkala, Katja A1 - Raitakari, Olli T. A1 - Jacobsson, Bo A1 - Zeggini, Eleftheria A1 - Dedoussis, George V. A1 - Teo, Yik-Ying A1 - Saw, Seang-Mei A1 - Montgomery, Grant W. A1 - Campbell, Harry A1 - Wilson, James F. A1 - Vrijkotte, Tanja G. M. A1 - Vrijheid, Martine A1 - de Geus, Eco J. C. N. A1 - Hayes, M. Geoffrey A1 - Kadarmideen, Haja N. A1 - Holm, Jens-Christian A1 - Beilin, Lawrence J. A1 - Pennell, Craig E. A1 - Heinrich, Joachim A1 - Adair, Linda S. A1 - Borja, Judith B. A1 - Mohlke, Karen L. A1 - Eriksson, Johan G. A1 - Widen, Elisabeth E. A1 - Hattersley, Andrew T. A1 - Spector, Tim D. A1 - Kaehoenen, Mika A1 - Viikari, Jorma S. A1 - Lehtimaeki, Terho A1 - Boomsma, Dorret I. A1 - Sebert, Sylvain A1 - Vollenweider, Peter A1 - Sorensen, Thorkild I. A. A1 - Bisgaard, Hans A1 - Bonnelykke, Klaus A1 - Murray, Jeffrey C. A1 - Melbye, Mads A1 - Nohr, Ellen A. A1 - Mook-Kanamori, Dennis O. A1 - Rivadeneira, Fernando A1 - Hofman, Albert A1 - Felix, Janine F. A1 - Jaddoe, Vincent W. V. A1 - Hansen, Torben A1 - Pisinger, Charlotta A1 - Vaag, Allan A. A1 - Pedersen, Oluf A1 - Uitterlinden, Andre G. A1 - Jarvelin, Marjo-Riitta A1 - Power, Christine A1 - Hypponen, Elina A1 - Scholtens, Denise M. A1 - Lowe, William L. A1 - Smith, George Davey A1 - Timpson, Nicholas J. A1 - Morris, Andrew P. A1 - Wareham, Nicholas J. A1 - Hakonarson, Hakon A1 - Grant, Struan F. A. A1 - Frayling, Timothy M. A1 - Lawlor, Debbie A. A1 - Njolstad, Pal R. A1 - Johansson, Stefan A1 - Ong, Ken K. A1 - McCarthy, Mark I. A1 - Perry, John R. B. A1 - Evans, David M. A1 - Freathy, Rachel M. T1 - Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors JF - Nature genetics N2 - Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming. Y1 - 2019 SN - 1061-4036 SN - 1546-1718 VL - 51 IS - 5 SP - 804 EP - + PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - von Websky, Karoline A1 - Reichetzeder, Christoph A1 - Tsuprykov, Oleg A1 - Gaballa, Mohamed Mahmoud Salem Ahmed A1 - Guo, Jingli A1 - Zeng, Shufei A1 - Delic, Denis A1 - Tammen, Harald A1 - Klein, Thomas A1 - Kleuser, Burkhard A1 - Hocher, Berthold T1 - Mechanisms of GLP-1 receptor-independent renoprotective effects of the dipeptidyl peptidase type 4 inhibitor linagliptin in GLP-1 receptor knockout mice with 5/6 nephrectomy JF - Kidney international : official journal of the International Society of Nephrology N2 - Dipeptidyl peptidase type 4 (DPP-4) inhibitors were reported to have beneficial effects in experimental models of chronic kidney disease. The underlying mechanisms are not completely understood. However, these effects could be mediated via the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP1R) pathway. Here we investigated the renal effects of the DPP-4 inhibitor linagliptin in Glp1r-/- knock out and wild-type mice with 5/6 nephrectomy (5/6Nx). Mice were allocated to groups: sham + wild type + placebo; 5/6Nx+ wild type + placebo; 5/6Nx+ wild type + linagliptin; sham + knock out+ placebo; 5/6Nx + knock out+ placebo; 5/6Nx + knock out+ linagliptin. 5/6Nx caused the development of renal interstitial fibrosis, significantly increased plasma cystatin C and creatinine levels and suppressed renal gelatinase/collagenase, matrix metalloproteinase-1 and -13 activities; effects counteracted by linagliptin treatment in wildtype and Glp1r-/- mice. Two hundred ninety-eight proteomics signals were differentially regulated in kidneys among the groups, with 150 signals specific to linagliptin treatment as shown by mass spectrometry. Treatment significantly upregulated three peptides derived from collagen alpha-1(I), thymosin beta 4 and heterogeneous nuclear ribonucleoprotein Al (HNRNPA1) and significantly downregulated one peptide derived from Y box binding protein-1 (YB-1). The proteomics results were further confirmed using western blot and immunofluorescence microscopy. Also, 5/6Nx led to significant up-regulation of renal transforming growth factor-beta 1 and pSMAD3 expression in wild type mice and linagliptin significantly counteracted this up-regulation in wild type and GIplr-/- mice. Thus, the renoprotective effects of linagliptin cannot solely be attributed to the GLP-1/GLP1R pathway, highlighting the importance of other signaling pathways (collagen I homeostasis, HNRNPA1,YB-1,thymosin beta 4 and TGF-beta 1) influenced by DPP-4 inhibition. KW - chronic kidney disease KW - collagen I KW - fibrosis KW - Glp1r(-/-) mice KW - HNRNPA1 KW - linagliptin KW - proteomic analysis KW - TGF-beta 1 KW - thymosin beta 4 KW - YB-1 Y1 - 2019 U6 - https://doi.org/10.1016/j.kint.2019.01.010 SN - 0085-2538 SN - 1523-1755 VL - 95 IS - 6 SP - 1373 EP - 1388 PB - Elsevier CY - New York ER - TY - JOUR A1 - Middeldorp, Christel M. A1 - Mahajan, Anubha A1 - Horikoshi, Momoko A1 - Robertson, Neil R. A1 - Beaumont, Robin N. A1 - Bradfield, Jonathan P. A1 - Bustamante, Mariona A1 - Cousminer, Diana L. A1 - Day, Felix R. A1 - De Silva, N. Maneka A1 - Guxens, Monica A1 - Mook-Kanamori, Dennis O. A1 - St Pourcain, Beate A1 - Warrington, Nicole M. A1 - Adair, Linda S. A1 - Ahlqvist, Emma A1 - Ahluwalia, Tarunveer Singh A1 - Almgren, Peter A1 - Ang, Wei A1 - Atalay, Mustafa A1 - Auvinen, Juha A1 - Bartels, Meike A1 - Beckmann, Jacques S. A1 - Bilbao, Jose Ramon A1 - Bond, Tom A1 - Borja, Judith B. A1 - Cavadino, Alana A1 - Charoen, Pimphen A1 - Chen, Zhanghua A1 - Coin, Lachlan A1 - Cooper, Cyrus A1 - Curtin, John A. A1 - Custovic, Adnan A1 - Das, Shikta A1 - Davies, Gareth E. A1 - Dedoussis, George V. A1 - Duijts, Liesbeth A1 - Eastwood, Peter R. A1 - Eliasen, Anders U. A1 - Elliott, Paul A1 - Eriksson, Johan G. A1 - Estivill, Xavier A1 - Fadista, Joao A1 - Fedko, Iryna O. A1 - Frayling, Timothy M. A1 - Gaillard, Romy A1 - Gauderman, W. James A1 - Geller, Frank A1 - Gilliland, Frank A1 - Gilsanz, Vincente A1 - Granell, Raquel A1 - Grarup, Niels A1 - Groop, Leif A1 - Hadley, Dexter A1 - Hakonarson, Hakon A1 - Hansen, Torben A1 - Hartman, Catharina A. A1 - Hattersley, Andrew T. A1 - Hayes, M. Geoffrey A1 - Hebebrand, Johannes A1 - Heinrich, Joachim A1 - Helgeland, Oyvind A1 - Henders, Anjali K. A1 - Henderson, John A1 - Henriksen, Tine B. A1 - Hirschhorn, Joel N. A1 - Hivert, Marie-France A1 - Hocher, Berthold A1 - Holloway, John W. A1 - Holt, Patrick A1 - Hottenga, Jouke-Jan A1 - Hypponen, Elina A1 - Iniguez, Carmen A1 - Johansson, Stefan A1 - Jugessur, Astanand A1 - Kahonen, Mika A1 - Kalkwarf, Heidi J. A1 - Kaprio, Jaakko A1 - Karhunen, Ville A1 - Kemp, John P. A1 - Kerkhof, Marjan A1 - Koppelman, Gerard H. A1 - Korner, Antje A1 - Kotecha, Sailesh A1 - Kreiner-Moller, Eskil A1 - Kulohoma, Benard A1 - Kumar, Ashish A1 - Kutalik, Zoltan A1 - Lahti, Jari A1 - Lappe, Joan M. A1 - Larsson, Henrik A1 - Lehtimaki, Terho A1 - Lewin, Alexandra M. A1 - Li, Jin A1 - Lichtenstein, Paul A1 - Lindgren, Cecilia M. A1 - Lindi, Virpi A1 - Linneberg, Allan A1 - Liu, Xueping A1 - Liu, Jun A1 - Lowe, William L. A1 - Lundstrom, Sebastian A1 - Lyytikainen, Leo-Pekka A1 - Ma, Ronald C. W. A1 - Mace, Aurelien A1 - Magi, Reedik A1 - Magnus, Per A1 - Mamun, Abdullah A. A1 - Mannikko, Minna A1 - Martin, Nicholas G. A1 - Mbarek, Hamdi A1 - McCarthy, Nina S. A1 - Medland, Sarah E. A1 - Melbye, Mads A1 - Melen, Erik A1 - Mohlke, Karen L. A1 - Monnereau, Claire A1 - Morgen, Camilla S. A1 - Morris, Andrew P. A1 - Murray, Jeffrey C. A1 - Myhre, Ronny A1 - Najman, Jackob M. A1 - Nivard, Michel G. A1 - Nohr, Ellen A. A1 - Nolte, Ilja M. A1 - Ntalla, Ioanna A1 - Oberfield, Sharon E. A1 - Oken, Emily A1 - Oldehinkel, Albertine J. A1 - Pahkala, Katja A1 - Palviainen, Teemu A1 - Panoutsopoulou, Kalliope A1 - Pedersen, Oluf A1 - Pennell, Craig E. A1 - Pershagen, Goran A1 - Pitkanen, Niina A1 - Plomin, Robert A1 - Power, Christine A1 - Prasad, Rashmi B. A1 - Prokopenko, Inga A1 - Pulkkinen, Lea A1 - Raikkonen, Katri A1 - Raitakari, Olli T. A1 - Reynolds, Rebecca M. A1 - Richmond, Rebecca C. A1 - Rivadeneira, Fernando A1 - Rodriguez, Alina A1 - Rose, Richard J. A1 - Salem, Rany A1 - Santa-Marina, Loreto A1 - Saw, Seang-Mei A1 - Schnurr, Theresia M. A1 - Scott, James G. A1 - Selzam, Saskia A1 - Shepherd, John A. A1 - Simpson, Angela A1 - Skotte, Line A1 - Sleiman, Patrick M. A. A1 - Snieder, Harold A1 - Sorensen, Thorkild I. A. A1 - Standl, Marie A1 - Steegers, Eric A. P. A1 - Strachan, David P. A1 - Straker, Leon A1 - Strandberg, Timo A1 - Taylor, Michelle A1 - Teo, Yik-Ying A1 - Thiering, Elisabeth A1 - Torrent, Maties A1 - Tyrrell, Jessica A1 - Uitterlinden, Andre G. A1 - van Beijsterveldt, Toos A1 - van der Most, Peter J. A1 - van Duijn, Cornelia M. A1 - Viikari, Jorma A1 - Vilor-Tejedor, Natalia A1 - Vogelezang, Suzanne A1 - Vonk, Judith M. A1 - Vrijkotte, Tanja G. M. A1 - Vuoksimaa, Eero A1 - Wang, Carol A. A1 - Watkins, William J. A1 - Wichmann, H-Erich A1 - Willemsen, Gonneke A1 - Williams, Gail M. A1 - Wilson, James F. A1 - Wray, Naomi R. A1 - Xu, Shujing A1 - Xu, Cheng-Jian A1 - Yaghootkar, Hanieh A1 - Yi, Lu A1 - Zafarmand, Mohammad Hadi A1 - Zeggini, Eleftheria A1 - Zemel, Babette S. A1 - Hinney, Anke A1 - Lakka, Timo A. A1 - Whitehouse, Andrew J. O. A1 - Sunyer, Jordi A1 - Widen, Elisabeth E. A1 - Feenstra, Bjarke A1 - Sebert, Sylvain A1 - Jacobsson, Bo A1 - Njolstad, Pal R. A1 - Stoltenberg, Camilla A1 - Smith, George Davey A1 - Lawlor, Debbie A. A1 - Paternoster, Lavinia A1 - Timpson, Nicholas J. A1 - Ong, Ken K. A1 - Bisgaard, Hans A1 - Bonnelykke, Klaus A1 - Jaddoe, Vincent W. V. A1 - Tiemeier, Henning A1 - Jarvelin, Marjo-Riitta A1 - Evans, David M. A1 - Perry, John R. B. A1 - Grant, Struan F. A. A1 - Boomsma, Dorret I. A1 - Freathy, Rachel M. A1 - McCarthy, Mark I. A1 - Felix, Janine F. T1 - The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia BT - design, results and future prospects JF - European journal of epidemiology N2 - The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites. KW - Genetics KW - Consortium KW - Childhood traits and disorders KW - Longitudinal Y1 - 2019 U6 - https://doi.org/10.1007/s10654-019-00502-9 SN - 0393-2990 SN - 1573-7284 VL - 34 IS - 3 SP - 279 EP - 300 PB - Springer CY - Dordrecht ER -