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1. Author Correction: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Jonathan P. Bradfeld, Rachel L. Kember, Anna Ulrich, Zhanna Balkhiyarova, Akram Alyass, Izzuddin M. Aris, Joshua A. Bell, K. Alaine Broadaway, Zhanghua Chen, Jin-Fang Chai, Neil M. Davies, Dietmar Fernandez-Orth, Mariona Bustamante, Ruby Fore, Amitavo Ganguli, Anni Heiskala, Jouke-Jan Hottenga, Carmen Íñiguez, Sayuko Kobes, Jaakko Leinonen, Estelle Lowry, Leo-Pekka Lyytikainen, Anubha Mahajan, Niina Pitkänen, Theresia M. Schnurr, Christian Theil Have, David P. Strachan, Elisabeth Thiering, Suzanne Vogelezang, Kaitlin H. Wade, Carol A. Wang, Andrew Wong, Louise Aas Holm, Alessandra Chesi, Catherine Choong, Miguel Cruz, Paul Elliott, Steve Franks, Christine Frithiof-Bøjsøe, W. James Gauderman, Joseph T. Glessner, Vicente Gilsanz, Kendra Griesman, Robert L. Hanson, Marika Kaakinen, Heidi Kalkwarf, Andrea Kelly, Joseph Kindler, Mika Kähönen, Carla Lanca, Joan Lappe, Nanette R. Lee, Shana McCormack, Frank D. Mentch, Jonathan A. Mitchell, Nina Mononen, Harri Niinikoski, Emily Oken, Katja Pahkala, Xueling Sim, Yik-Ying Teo, Leslie J. Baier, Toos van Beijsterveldt, Linda S. Adair, Dorret I. Boomsma, Eco de Geus, Mònica Guxens, Johan G. Eriksson, Janine F. Felix, Frank D. Gilliland, Penn Medicine Biobank, Torben Hansen, Rebecca Hardy, Marie-France Hivert, Jens-Christian Holm, Vincent W. V. Jaddoe, Marjo-Riitta Järvelin, Terho Lehtimäki, David A. Mackey, David Meyre, Karen L. Mohlke, Juha Mykkänen, Sharon Oberfeld, Craig E. Pennell, John R. B. Perry, Olli Raitakari, Fernando Rivadeneira, Seang-Mei Saw, Sylvain Sebert, John A. Shepherd, Marie Standl, Thorkild I. A. Sørensen, Nicholas J. Timpson, Maties Torrent, Gonneke Willemsen, Elina Hypponen, Chris Power, The Early Growth Genetics Consortium, Mark I. McCarthy, Rachel M. Freathy, Elisabeth Widén, Hakon Hakonarson, Inga Prokopenko, Benjamin F. Voight, Babette S. Zemel, Struan F. A. Grant, and Diana L. Cousminer

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Published
2024
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2. Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Author

Jonathan P. Bradfield, Rachel L. Kember, Anna Ulrich, Zhanna Balkhiyarova, Akram Alyass, Izzuddin M. Aris, Joshua A. Bell, K. Alaine Broadaway, Zhanghua Chen, Jin-Fang Chai, Neil M. Davies, Dietmar Fernandez-Orth, Mariona Bustamante, Ruby Fore, Amitavo Ganguli, Anni Heiskala, Jouke-Jan Hottenga, Carmen Íñiguez, Sayuko Kobes, Jaakko Leinonen, Estelle Lowry, Leo-Pekka Lyytikainen, Anubha Mahajan, Niina Pitkänen, Theresia M. Schnurr, Christian Theil Have, David P. Strachan, Elisabeth Thiering, Suzanne Vogelezang, Kaitlin H. Wade, Carol A. Wang, Andrew Wong, Louise Aas Holm, Alessandra Chesi, Catherine Choong, Miguel Cruz, Paul Elliott, Steve Franks, Christine Frithioff-Bøjsøe, W. James Gauderman, Joseph T. Glessner, Vicente Gilsanz, Kendra Griesman, Robert L. Hanson, Marika Kaakinen, Heidi Kalkwarf, Andrea Kelly, Joseph Kindler, Mika Kähönen, Carla Lanca, Joan Lappe, Nanette R. Lee, Shana McCormack, Frank D. Mentch, Jonathan A. Mitchell, Nina Mononen, Harri Niinikoski, Emily Oken, Katja Pahkala, Xueling Sim, Yik-Ying Teo, Leslie J. Baier, Toos van Beijsterveldt, Linda S. Adair, Dorret I. Boomsma, Eco de Geus, Mònica Guxens, Johan G. Eriksson, Janine F. Felix, Frank D. Gilliland, Penn Medicine Biobank, Torben Hansen, Rebecca Hardy, Marie-France Hivert, Jens-Christian Holm, Vincent W. V. Jaddoe, Marjo-Riitta Järvelin, Terho Lehtimäki, David A. Mackey, David Meyre, Karen L. Mohlke, Juha Mykkänen, Sharon Oberfield, Craig E. Pennell, John R. B. Perry, Olli Raitakari, Fernando Rivadeneira, Seang-Mei Saw, Sylvain Sebert, John A. Shepherd, Marie Standl, Thorkild I. A. Sørensen, Nicholas J. Timpson, Maties Torrent, Gonneke Willemsen, Elina Hypponen, Chris Power, The Early Growth Genetics Consortium, Mark I. McCarthy, Rachel M. Freathy, Elisabeth Widén, Hakon Hakonarson, Inga Prokopenko, Benjamin F. Voight, Babette S. Zemel, Struan F. A. Grant, and Diana L. Cousminer

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. Conclusion We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern.

Published
2024
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3. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Author

Thomas W. Winkler, Humaira Rasheed, Alexander Teumer, Mathias Gorski, Bryce X. Rowan, Kira J. Stanzick, Laurent F. Thomas, Adrienne Tin, Anselm Hoppmann, Audrey Y. Chu, Bamidele Tayo, Chris H. L. Thio, Daniele Cusi, Jin-Fang Chai, Karsten B. Sieber, Katrin Horn, Man Li, Markus Scholz, Massimiliano Cocca, Matthias Wuttke, Peter J. van der Most, Qiong Yang, Sahar Ghasemi, Teresa Nutile, Yong Li, Giulia Pontali, Felix Günther, Abbas Dehghan, Adolfo Correa, Afshin Parsa, Agnese Feresin, Aiko P. J. de Vries, Alan B. Zonderman, Albert V. Smith, Albertine J. Oldehinkel, Alessandro De Grandi, Alexander R. Rosenkranz, Andre Franke, Andrej Teren, Andres Metspalu, Andrew A. Hicks, Andrew P. Morris, Anke Tönjes, Anna Morgan, Anna I. Podgornaia, Annette Peters, Antje Körner, Anubha Mahajan, Archie Campbell, Barry I. Freedman, Beatrice Spedicati, Belen Ponte, Ben Schöttker, Ben Brumpton, Bernhard Banas, Bernhard K. Krämer, Bettina Jung, Bjørn Olav Åsvold, Blair H. Smith, Boting Ning, Brenda W. J. H. Penninx, Brett R. Vanderwerff, Bruce M. Psaty, Candace M. Kammerer, Carl D. Langefeld, Caroline Hayward, Cassandra N. Spracklen, Cassianne Robinson-Cohen, Catharina A. Hartman, Cecilia M. Lindgren, Chaolong Wang, Charumathi Sabanayagam, Chew-Kiat Heng, Chiara Lanzani, Chiea-Chuen Khor, Ching-Yu Cheng, Christian Fuchsberger, Christian Gieger, Christian M. Shaffer, Christina-Alexandra Schulz, Cristen J. Willer, Daniel I. Chasman, Daniel F. Gudbjartsson, Daniela Ruggiero, Daniela Toniolo, Darina Czamara, David J. Porteous, Dawn M. Waterworth, Deborah Mascalzoni, Dennis O. Mook-Kanamori, Dermot F. Reilly, E. Warwick Daw, Edith Hofer, Eric Boerwinkle, Erika Salvi, Erwin P. Bottinger, E-Shyong Tai, Eulalia Catamo, Federica Rizzi, Feng Guo, Fernando Rivadeneira, Franco Guilianini, Gardar Sveinbjornsson, Georg Ehret, Gerard Waeber, Ginevra Biino, Giorgia Girotto, Giorgio Pistis, Girish N. Nadkarni, Graciela E. Delgado, Grant W. Montgomery, Harold Snieder, Harry Campbell, Harvey D. White, He Gao, Heather M. Stringham, Helena Schmidt, Hengtong Li, Hermann Brenner, Hilma Holm, Holgen Kirsten, Holly Kramer, Igor Rudan, Ilja M. Nolte, Ioanna Tzoulaki, Isleifur Olafsson, Jade Martins, James P. Cook, James F. Wilson, Jan Halbritter, Janine F. Felix, Jasmin Divers, Jaspal S. Kooner, Jeannette Jen-Mai Lee, Jeffrey O’Connell, Jerome I. Rotter, Jianjun Liu, Jie Xu, Joachim Thiery, Johan Ärnlöv, Johanna Kuusisto, Johanna Jakobsdottir, Johanne Tremblay, John C. Chambers, John B. Whitfield, John M. Gaziano, Jonathan Marten, Josef Coresh, Jost B. Jonas, Josyf C. Mychaleckyj, Kaare Christensen, Kai-Uwe Eckardt, Karen L. Mohlke, Karlhans Endlich, Katalin Dittrich, Kathleen A. Ryan, Kenneth M. Rice, Kent D. Taylor, Kevin Ho, Kjell Nikus, Koichi Matsuda, Konstantin Strauch, Kozeta Miliku, Kristian Hveem, Lars Lind, Lars Wallentin, Laura M. Yerges-Armstrong, Laura M. Raffield, Lawrence S. Phillips, Lenore J. Launer, Leo-Pekka Lyytikäinen, Leslie A. Lange, Lorena Citterio, Lucija Klaric, M. Arfan Ikram, Marcus Ising, Marcus E. Kleber, Margherita Francescatto, Maria Pina Concas, Marina Ciullo, Mario Piratsu, Marju Orho-Melander, Markku Laakso, Markus Loeffler, Markus Perola, Martin H. de Borst, Martin Gögele, Martina La Bianca, Mary Ann Lukas, Mary F. Feitosa, Mary L. Biggs, Mary K. Wojczynski, Maryam Kavousi, Masahiro Kanai, Masato Akiyama, Masayuki Yasuda, Matthias Nauck, Melanie Waldenberger, Miao-Li Chee, Miao-Ling Chee, Michael Boehnke, Michael H. Preuss, Michael Stumvoll, Michael A. Province, Michele K. Evans, Michelle L. O’Donoghue, Michiaki Kubo, Mika Kähönen, Mika Kastarinen, Mike A. Nalls, Mikko Kuokkanen, Mohsen Ghanbari, Murielle Bochud, Navya Shilpa Josyula, Nicholas G. Martin, Nicholas Y. Q. Tan, Nicholette D. Palmer, Nicola Pirastu, Nicole Schupf, Niek Verweij, Nina Hutri-Kähönen, Nina Mononen, Nisha Bansal, Olivier Devuyst, Olle Melander, Olli T. Raitakari, Ozren Polasek, Paolo Manunta, Paolo Gasparini, Pashupati P. Mishra, Patrick Sulem, Patrik K. E. Magnusson, Paul Elliott, Paul M. Ridker, Pavel Hamet, Per O. Svensson, Peter K. Joshi, Peter Kovacs, Peter P. Pramstaller, Peter Rossing, Peter Vollenweider, Pim van der Harst, Rajkumar Dorajoo, Ralene Z. H. Sim, Ralph Burkhardt, Ran Tao, Raymond Noordam, Reedik Mägi, Reinhold Schmidt, Renée de Mutsert, Rico Rueedi, Rob M. van Dam, Robert J. Carroll, Ron T. Gansevoort, Ruth J. F. Loos, Sala Cinzia Felicita, Sanaz Sedaghat, Sandosh Padmanabhan, Sandra Freitag-Wolf, Sarah A. Pendergrass, Sarah E. Graham, Scott D. Gordon, Shih-Jen Hwang, Shona M. Kerr, Simona Vaccargiu, Snehal B. Patil, Stein Hallan, Stephan J. L. Bakker, Su-Chi Lim, Susanne Lucae, Suzanne Vogelezang, Sven Bergmann, Tanguy Corre, Tarunveer S. Ahluwalia, Terho Lehtimäki, Thibaud S. Boutin, Thomas Meitinger, Tien-Yin Wong, Tobias Bergler, Ton J. Rabelink, Tõnu Esko, Toomas Haller, Unnur Thorsteinsdottir, Uwe Völker, Valencia Hui Xian Foo, Veikko Salomaa, Veronique Vitart, Vilmantas Giedraitis, Vilmundur Gudnason, Vincent W. V. Jaddoe, Wei Huang, Weihua Zhang, Wen Bin Wei, Wieland Kiess, Winfried März, Wolfgang Koenig, Wolfgang Lieb, Xin Gao, Xueling Sim, Ya Xing Wang, Yechiel Friedlander, Yih-Chung Tham, Yoichiro Kamatani, Yukinori Okada, Yuri Milaneschi, Zhi Yu, Lifelines cohort study, DiscovEHR/MyCode study, VA Million Veteran Program, Klaus J. Stark, Kari Stefansson, Carsten A. Böger, Adriana M. Hung, Florian Kronenberg, Anna Köttgen, Cristian Pattaro, and Iris M. Heid

Subjects
Biology (General), QH301-705.5
Abstract

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.

Published
2022
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4. Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes

Author

Suzanne Vogelezang, Jonathan P. Bradfield, the Early Growth Genetics Consortium, Struan F. A. Grant, Janine F. Felix, and Vincent W. V. Jaddoe

Subjects
Head circumference, Genome-wide association study, Genetic correlations, Infancy, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Head circumference is associated with intelligence and tracks from childhood into adulthood. Methods We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. Results Seven loci reached genome-wide significance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes. Conclusions The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.

Published
2022
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5. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Author

Alexander Teumer, Yong Li, Sahar Ghasemi, Bram P. Prins, Matthias Wuttke, Tobias Hermle, Ayush Giri, Karsten B. Sieber, Chengxiang Qiu, Holger Kirsten, Adrienne Tin, Audrey Y. Chu, Nisha Bansal, Mary F. Feitosa, Lihua Wang, Jin-Fang Chai, Massimiliano Cocca, Christian Fuchsberger, Mathias Gorski, Anselm Hoppmann, Katrin Horn, Man Li, Jonathan Marten, Damia Noce, Teresa Nutile, Sanaz Sedaghat, Gardar Sveinbjornsson, Bamidele O. Tayo, Peter J. van der Most, Yizhe Xu, Zhi Yu, Lea Gerstner, Johan Ärnlöv, Stephan J. L. Bakker, Daniela Baptista, Mary L. Biggs, Eric Boerwinkle, Hermann Brenner, Ralph Burkhardt, Robert J. Carroll, Miao-Li Chee, Miao-Ling Chee, Mengmeng Chen, Ching-Yu Cheng, James P. Cook, Josef Coresh, Tanguy Corre, John Danesh, Martin H. de Borst, Alessandro De Grandi, Renée de Mutsert, Aiko P. J. de Vries, Frauke Degenhardt, Katalin Dittrich, Jasmin Divers, Kai-Uwe Eckardt, Georg Ehret, Karlhans Endlich, Janine F. Felix, Oscar H. Franco, Andre Franke, Barry I. Freedman, Sandra Freitag-Wolf, Ron T. Gansevoort, Vilmantas Giedraitis, Martin Gögele, Franziska Grundner-Culemann, Daniel F. Gudbjartsson, Vilmundur Gudnason, Pavel Hamet, Tamara B. Harris, Andrew A. Hicks, Hilma Holm, Valencia Hui Xian Foo, Shih-Jen Hwang, M. Arfan Ikram, Erik Ingelsson, Vincent W. V. Jaddoe, Johanna Jakobsdottir, Navya Shilpa Josyula, Bettina Jung, Mika Kähönen, Chiea-Chuen Khor, Wieland Kiess, Wolfgang Koenig, Antje Körner, Peter Kovacs, Holly Kramer, Bernhard K. Krämer, Florian Kronenberg, Leslie A. Lange, Carl D. Langefeld, Jeannette Jen-Mai Lee, Terho Lehtimäki, Wolfgang Lieb, Su-Chi Lim, Lars Lind, Cecilia M. Lindgren, Jianjun Liu, Markus Loeffler, Leo-Pekka Lyytikäinen, Anubha Mahajan, Joseph C. Maranville, Deborah Mascalzoni, Barbara McMullen, Christa Meisinger, Thomas Meitinger, Kozeta Miliku, Dennis O. Mook-Kanamori, Martina Müller-Nurasyid, Josyf C. Mychaleckyj, Matthias Nauck, Kjell Nikus, Boting Ning, Raymond Noordam, Jeffrey O’ Connell, Isleifur Olafsson, Nicholette D. Palmer, Annette Peters, Anna I. Podgornaia, Belen Ponte, Tanja Poulain, Peter P. Pramstaller, Ton J. Rabelink, Laura M. Raffield, Dermot F. Reilly, Rainer Rettig, Myriam Rheinberger, Kenneth M. Rice, Fernando Rivadeneira, Heiko Runz, Kathleen A. Ryan, Charumathi Sabanayagam, Kai-Uwe Saum, Ben Schöttker, Christian M. Shaffer, Yuan Shi, Albert V. Smith, Konstantin Strauch, Michael Stumvoll, Benjamin B. Sun, Silke Szymczak, E-Shyong Tai, Nicholas Y. Q. Tan, Kent D. Taylor, Andrej Teren, Yih-Chung Tham, Joachim Thiery, Chris H. L. Thio, Hauke Thomsen, Unnur Thorsteinsdottir, Anke Tönjes, Johanne Tremblay, André G. Uitterlinden, Pim van der Harst, Niek Verweij, Suzanne Vogelezang, Uwe Völker, Melanie Waldenberger, Chaolong Wang, Otis D. Wilson, Charlene Wong, Tien-Yin Wong, Qiong Yang, Masayuki Yasuda, Shreeram Akilesh, Murielle Bochud, Carsten A. Böger, Olivier Devuyst, Todd L. Edwards, Kevin Ho, Andrew P. Morris, Afshin Parsa, Sarah A. Pendergrass, Bruce M. Psaty, Jerome I. Rotter, Kari Stefansson, James G. Wilson, Katalin Susztak, Harold Snieder, Iris M. Heid, Markus Scholz, Adam S. Butterworth, Adriana M. Hung, Cristian Pattaro, and Anna Köttgen

Subjects
Science
Abstract

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Published
2019
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6. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

Author

Xueping Liu, Dorte Helenius, Line Skotte, Robin N. Beaumont, Matthias Wielscher, Frank Geller, Julius Juodakis, Anubha Mahajan, Jonathan P. Bradfield, Frederick T. J. Lin, Suzanne Vogelezang, Mariona Bustamante, Tarunveer S. Ahluwalia, Niina Pitkänen, Carol A. Wang, Jonas Bacelis, Maria C. Borges, Ge Zhang, Bruce A. Bedell, Robert M. Rossi, Kristin Skogstrand, Shouneng Peng, Wesley K. Thompson, Vivek Appadurai, Debbie A. Lawlor, Ilkka Kalliala, Christine Power, Mark I. McCarthy, Heather A. Boyd, Mary L. Marazita, Hakon Hakonarson, M. Geoffrey Hayes, Denise M. Scholtens, Fernando Rivadeneira, Vincent W. V. Jaddoe, Rebecca K. Vinding, Hans Bisgaard, Bridget A. Knight, Katja Pahkala, Olli Raitakari, Øyvind Helgeland, Stefan Johansson, Pål R. Njølstad, João Fadista, Andrew J. Schork, Ron Nudel, Daniel E. Miller, Xiaoting Chen, Matthew T. Weirauch, Preben Bo Mortensen, Anders D. Børglum, Merete Nordentoft, Ole Mors, Ke Hao, Kelli K. Ryckman, David M. Hougaard, Leah C. Kottyan, Craig E. Pennell, Leo-Pekka Lyytikainen, Klaus Bønnelykke, Martine Vrijheid, Janine F. Felix, William L. Lowe, Struan F. A. Grant, Elina Hyppönen, Bo Jacobsson, Marjo-Riitta Jarvelin, Louis J. Muglia, Jeffrey C. Murray, Rachel M. Freathy, Thomas M. Werge, Mads Melbye, Alfonso Buil, and Bjarke Feenstra

Subjects
Science
Abstract

Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

Published
2019
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7. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

Author

Suzanne Vogelezang, Jonathan P Bradfield, Tarunveer S Ahluwalia, John A Curtin, Timo A Lakka, Niels Grarup, Markus Scholz, Peter J van der Most, Claire Monnereau, Evie Stergiakouli, Anni Heiskala, Momoko Horikoshi, Iryna O Fedko, Natalia Vilor-Tejedor, Diana L Cousminer, Marie Standl, Carol A Wang, Jorma Viikari, Frank Geller, Carmen Íñiguez, Niina Pitkänen, Alessandra Chesi, Jonas Bacelis, Loic Yengo, Maties Torrent, Ioanna Ntalla, Øyvind Helgeland, Saskia Selzam, Judith M Vonk, Mohammed H Zafarmand, Barbara Heude, Ismaa Sadaf Farooqi, Akram Alyass, Robin N Beaumont, Christian T Have, Peter Rzehak, Jose Ramon Bilbao, Theresia M Schnurr, Inês Barroso, Klaus Bønnelykke, Lawrence J Beilin, Lisbeth Carstensen, Marie-Aline Charles, Bo Chawes, Karine Clément, Ricardo Closa-Monasterolo, Adnan Custovic, Johan G Eriksson, Joaquin Escribano, Maria Groen-Blokhuis, Veit Grote, Dariusz Gruszfeld, Hakon Hakonarson, Torben Hansen, Andrew T Hattersley, Mette Hollensted, Jouke-Jan Hottenga, Elina Hyppönen, Stefan Johansson, Raimo Joro, Mika Kähönen, Ville Karhunen, Wieland Kiess, Bridget A Knight, Berthold Koletzko, Andreas Kühnapfel, Kathrin Landgraf, Jean-Paul Langhendries, Terho Lehtimäki, Jaakko T Leinonen, Aihuali Li, Virpi Lindi, Estelle Lowry, Mariona Bustamante, Carolina Medina-Gomez, Mads Melbye, Kim F Michaelsen, Camilla S Morgen, Trevor A Mori, Tenna R H Nielsen, Harri Niinikoski, Albertine J Oldehinkel, Katja Pahkala, Kalliope Panoutsopoulou, Oluf Pedersen, Craig E Pennell, Christine Power, Sijmen A Reijneveld, Fernando Rivadeneira, Angela Simpson, Peter D Sly, Jakob Stokholm, Kook K Teo, Elisabeth Thiering, Nicholas J Timpson, André G Uitterlinden, Catharina E M van Beijsterveldt, Barbera D C van Schaik, Marc Vaudel, Elvira Verduci, Rebecca K Vinding, Mandy Vogel, Eleftheria Zeggini, Sylvain Sebert, Mads V Lind, Christopher D Brown, Loreto Santa-Marina, Eva Reischl, Christine Frithioff-Bøjsøe, David Meyre, Eleanor Wheeler, Ken Ong, Ellen A Nohr, Tanja G M Vrijkotte, Gerard H Koppelman, Robert Plomin, Pål R Njølstad, George D Dedoussis, Philippe Froguel, Thorkild I A Sørensen, Bo Jacobsson, Rachel M Freathy, Babette S Zemel, Olli Raitakari, Martine Vrijheid, Bjarke Feenstra, Leo-Pekka Lyytikäinen, Harold Snieder, Holger Kirsten, Patrick G Holt, Joachim Heinrich, Elisabeth Widén, Jordi Sunyer, Dorret I Boomsma, Marjo-Riitta Järvelin, Antje Körner, George Davey Smith, Jens-Christian Holm, Mustafa Atalay, Clare Murray, Hans Bisgaard, Mark I McCarthy, Early Growth Genetics Consortium, Vincent W V Jaddoe, Struan F A Grant, and Janine F Felix

Subjects
Genetics, QH426-470
Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values

Published
2020
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8. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration

Author

Maria Carolina Borges, M. Geoffrey Hayes, Ke Hao, Carol A. Wang, Marjo-Riitta Järvelin, Niina Pitkänen, Ilkka Kalliala, Mariona Bustamante, Olli T. Raitakari, Bridget A. Knight, Robin N Beaumont, Matthew T. Weirauch, Line Skotte, Matthias Wielscher, Mark I. McCarthy, Klaus Bønnelykke, Vincent W. V. Jaddoe, Elina Hyppönen, Ole Mors, Tarunveer S. Ahluwalia, Thomas Werge, Frank Geller, Jonathan P. Bradfield, Vivek Appadurai, Kristin Skogstrand, Merete Nordentoft, Suzanne Vogelezang, Preben Bo Mortensen, Xueping Liu, Daniel Miller, Hakon Hakonarson, João Fadista, Pål R. Njølstad, Leah C. Kottyan, Wesley K. Thompson, Bruce Bedell, Katja Pahkala, Stefan Johansson, Dorte Helenius, Louis J. Muglia, Janine F. Felix, Rachel M. Freathy, Heather A. Boyd, Bjarke Feenstra, Ge Zhang, Anubha Mahajan, Alfonso Buil, Bo Jacobsson, Martine Vrijheid, Frederick T.J. Lin, William L. Lowe, Mads Melbye, Ron Nudel, Denise M. Scholtens, Julius Juodakis, Shouneng Peng, Christine Power, Andrew J. Schork, Jeffrey C. Murray, David M. Hougaard, Craig E. Pennell, Øyvind Helgeland, Struan F.A. Grant, Kelli K. Ryckman, Mary L. Marazita, Xiaoting Chen, Jonas Bacelis, Anders D. Børglum, Debbie A Lawlor, Hans Bisgaard, Robert M. Rossi, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Rebecca K. Vinding, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Clinicum, Helsinki University Hospital Area, Epidemiology, Internal Medicine, Pediatrics, Erasmus MC other, Liu, Xueping, Helenius, Dorte, Skotte, Line, Beaumont, Robin N, Hyppönen, Elina, Feenstra, Bjarke, and UNIVERSITY OF OULU

Subjects
0301 basic medicine, LD SCORE REGRESSION, General Physics and Astronomy, Genome-wide association study, 02 engineering and technology, Reproductive health and childbirth, Bioinformatics, Low Birth Weight and Health of the Newborn, Genome-wide association studies, 3123 Gynaecology and paediatrics, Pregnancy, Genotype, Infant Mortality, Genetics research, 2.1 Biological and endogenous factors, WIDE ASSOCIATION, GWAS, FUNCTIONAL VARIATION, Aetiology, lcsh:Science, Pediatric, Multidisciplinary, Genome, Gestational age, Single Nucleotide, 021001 nanoscience & nanotechnology, 3. Good health, Multidisciplinary Sciences, Chromosomes, Human, Pair 2, Pair 2, Gestation, Science & Technology - Other Topics, Premature Birth, Cytokines, Female, 0210 nano-technology, Human, Reproductive signs and symptoms, EXPRESSION, PRETERM BIRTH, Science, Reproductive biology, Locus (genetics), Gestational Age, Biology, Polymorphism, Single Nucleotide, SEQUENCE, Article, General Biochemistry, Genetics and Molecular Biology, Chromosomes, 03 medical and health sciences, AGE, Fetus, Preterm, medicine, Genetics, SNP, Humans, Polymorphism, Science & Technology, Genome, Human, Human Genome, Infant, Newborn, Infant, General Chemistry, Perinatal Period - Conditions Originating in Perinatal Period, medicine.disease, Newborn, 030104 developmental biology, Good Health and Well Being, lcsh:Q, WEIGHT, 3111 Biomedicine, HAPLOTYPES, Genome-Wide Association Study
Abstract

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality., Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

Published
2019
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9. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

Author

Inês Barroso, Peter D. Sly, Jose Ramon Bilbao, Nicholas J. Timpson, Johan G. Eriksson, Maria M. Groen-Blokhuis, Sijmen A. Reijneveld, Dariusz Gruszfeld, George Davey Smith, Christine Power, Eva Reischl, Mandy Vogel, Andrew T. Hattersley, Øyvind Helgeland, Niina Pitkänen, Akram Alyass, Jean-Paul Langhendries, Elina Hyppönen, Kathrin Landgraf, Loreto Santa-Marina, Frank Geller, Christopher D. Brown, Elvira Verduci, Katja Pahkala, Olli T. Raitakari, Joaquin Escribano, Torben Hansen, Hakon Hakonarson, Barbara Heude, Bridget A. Knight, Maties Torrent, Robin N Beaumont, Judith M. Vonk, Estelle Lowry, Patrick G. Holt, Harold Snieder, Carol A. Wang, Mark I. McCarthy, Christine Frithioff-Bøjsøe, Tanja G. M. Vrijkotte, Natalia Vilor-Tejedor, Lisbeth Carstensen, Catharina E. M. van Beijsterveldt, Ville Karhunen, Virpi Lindi, Marjo-Riitta Järvelin, Tarunveer S. Ahluwalia, Jordi Sunyer, Jaakko T. Leinonen, Clare S. Murray, Klaus Bønnelykke, Thorkild I. A. Sørensen, André G. Uitterlinden, Janine F. Felix, John A. Curtin, Mika Kähönen, Jorma Viikari, Leo-Pekka Lyytikäinen, Oluf Pedersen, Carmen Iñiguez, Harri Niinikoski, Wieland Kiess, Kim F. Michaelsen, Evie Stergiakouli, Anni Heiskala, Alessandra Chesi, Craig E. Pennell, Mohammed H Zafarmand, Peter Rzehak, Kook K Teo, Aihuali Li, Marie Standl, Veit Grote, Momoko Horikoshi, Ellen A. Nohr, Eleanor Wheeler, Rachel M. Freathy, Iryna O. Fedko, Gerard H. Koppelman, Elisabeth Widen, Jens-Christian Holm, Raimo Joro, David Meyre, Mustafa Atalay, Theresia M. Schnurr, Camilla Schmidt Morgen, Adnan Custovic, Niels Grarup, Trevor A. Mori, Terho Lehtimäki, Christian Theil Have, Angela Simpson, Mads Melbye, Bjarke Feenstra, Lawrence J. Beilin, Stefan Johansson, Ioanna Ntalla, Martine Vrijheid, Mariona Bustamante, George Dedoussis, Sylvain Sebert, Jonas Bacelis, Carolina Medina-Gomez, Elisabeth Thiering, Ken K. Ong, Eleftheria Zeggini, Berthold Koletzko, Karine Clément, Bo L. Chawes, Mette Hollensted, Babette S. Zemel, Markus Scholz, Holger Kirsten, Antje Körner, Albertine J. Oldehinkel, Barbera D. C. van Schaik, Philippe Froguel, Vincent W. V. Jaddoe, Dorret I. Boomsma, Struan F.A. Grant, Loic Yengo, Jonathan P. Bradfield, Tenna Ruest Haarmark Nielsen, Suzanne Vogelezang, Jakob Stokholm, Pål R. Njølstad, Bo Jacobsson, Marc Vaudel, Peter J. van der Most, Andreas Kühnapfel, Mads Vendelbo Lind, Timo A. Lakka, Saskia Selzam, Robert Plomin, Marie-Aline Charles, Jouke-Jan Hottenga, Kalliope Panoutsopoulou, Fernando Rivadeneira, Rebecca K. Vinding, Hans Bisgaard, I. S. Farooqi, Joachim Heinrich, Diana L. Cousminer, Ricardo Closa-Monasterolo, Claire Monnereau, European Commission, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Epidemiology and Data Science, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, APH - Global Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, ARD - Amsterdam Reproduction and Development, APH - Methodology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Amsterdam Cardiovascular Sciences, Public and occupational health, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Children’s Hospital of Philadelphia (CHOP ), Herlev and Gentofte Hospital, Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], University of Kuopio, University of Copenhagen = Københavns Universitet (KU), Universität Leipzig [Leipzig], University Medical Center Groningen [Groningen] (UMCG), University of Bristol [Bristol], Université d'Oulu, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Vrije Universiteit Brussel (VUB), CIBER de Epidemiología y Salud Pública (CIBERESP), Helmholtz-Zentrum München (HZM), University of Newcastle [Australia] (UoN), Turku University Hospital (TYKS), Statens Serum Institut [Copenhagen], Sahlgrenska Academy at University of Gothenburg [Göteborg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Queen Mary University of London (QMUL), Norwegian Institute of Public Health [Oslo] (NIPH), King‘s College London, University of Groningen [Groningen], University of Amsterdam [Amsterdam] (UvA), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Cambridge [UK] (CAM), McMaster University [Hamilton, Ontario], University of Exeter, Ludwig-Maximilians-Universität München (LMU), University of the Basque Country [Bizkaia] (UPV/EHU), The Wellcome Trust Sanger Institute [Cambridge], The University of Western Australia (UWA), Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universitat Rovira i Virgili, Imperial College London, University of Helsinki, Vrije Universiteit Amsterdam [Amsterdam] (VU), University College of London [London] (UCL), University of Bergen (UiB), University of Tampere [Finland], University of Oulu, Copenhagen University Hospital, University of Turku, University of Queensland [Brisbane], Haukeland University Hospital, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust University College London Wellcome 090532106130098381203141212259WT206194United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)U01DK105535National Institute for Health Research (NIHR)NF-SI-0617-10090Netherlands Organization for Health Research and DevelopmentTOP 40-00812-9811010American Diabetes Association1-17-PDF-077Daniel B. Burke Chair for Diabetes Research United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAR01 HD058886Agencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR)2017 FI_B 00636Generalitat de Catalunya -Fons Social Europeu European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG) 322605Oak Foundation Fellowship Wellcome TrustEuropean CommissionWT104150098497/Z/12/ZRoyal Society of LondonEuropean CommissionWT104150Wellcome Trust098395/Z/12/ZNatural Resources CanadaCanadian Forest ServiceCanada Research Chairs Finnish Cultural Foundation KNAW Academy Professor Award PAH/6635TARGET Danish Diabetes Academy Copenhagen Graduate School of Health and Medical Sciences Netherlands Organization for Health Research and Development (VIDI) 016.136.361European Research Council (ERC)European Commission648916European Research Council (ERC)European Commission UK Research & Innovation (UKRI)Medical Research Council UK (MRC)European CommissionMRC_MC_UU_12012/5MC_UU_00011/1National Institute for Health Research (NIHR) Botnar Foundation Bernard Wolfe Health Neuroscience Endowment European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO 279153University of Bristol UK Research & Innovation (UKRI)Medical Research Council UK (MRC)MC_UU_00011/1MC_UU_00011/3French National Agency of Research, F-CRIN/FORCE, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Helsinki University Hospital Area, Genomics of Sex Differences, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, University of Copenhagen = Københavns Universitet (UCPH), Universität Leipzig, University of Oxford, Helmholtz Zentrum München = German Research Center for Environmental Health, University of Newcastle [Callaghan, Australia] (UoN), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Felix, Janine F [0000-0002-9801-5774], Apollo - University of Cambridge Repository, Biological Psychology, APH - Mental Health, Felix, Janine F. [0000-0002-9801-5774], Tampere University, Tampere University Hospital Catchment Area, Department of Clinical Physiology and Nuclear Medicine, Clinical Medicine, Department of Clinical Chemistry, Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Life Course Epidemiology (LCE), Vogelezang, Suzanne, Bradfield, Jonathan P, Ahluwalia, Tarunveer S, Curtin, John A, Hyppönen, Elina, Felix, JF, and Early Growth Genetics Consortium

Subjects
Male, Genetic-variation, Nedd4 Ubiquitin Protein Ligases, Pooled Analysis, Blood Pressure, 0302 clinical medicine, Human genetics, Mendelian Randomization, Young adult, Child, health care economics and organizations, Body mass index, Adiposity, Genetics & Heredity, 0303 health sciences, Statistics, 1184 Genetics, developmental biology, physiology, Genomics, adulto, 3. Good health, Cardiovascular Diseases, Child, Preschool, Physical Sciences, Menarche, genetic-variation, presión sanguínea, Monosaccharide Transport Proteins, Genetic loci, education, enfermedades cardiovasculares, Prostate-specific Antigen, Genetic correlation, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Diabetes Mellitus, Genetics, Humans, prostate-specific antigen, Statistical Methods, Molecular Biology, Ecology, Evolution, Behavior and Systematics, childhood, 0604 Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, Early Growth Genetics Consortium, Biology and Life Sciences, Computational Biology, nutritional and metabolic diseases, Single nucleotide polymorphisms, Mendelian Randomization Analysis, Biological Tissue, Diabetes Mellitus, Type 2, estudio de asociación genómica completa, genetic factors, mendelian randomization, análisis de la aleatorización mendeliana, proteínas de transporte de monosacáridos, 030217 neurology & neurosurgery, Mathematics, Demography, Developmental Biology, Cardiovascular Risk, Cancer Research, obesity, Physiology, humanos, adolescente, Overweight, QH426-470, Genome-wide association studies, Waist–hip ratio, Mathematical and Statistical Techniques, Medicine and Health Sciences, body mass index (BMI), Genetics of disease, Genetics (clinical), 2. Zero hunger, adiposity, Metaanalysis, Physiological Parameters, Connective Tissue, Female, medicine.symptom, Anatomy, pooled analysis, Life Sciences & Biomedicine, Research Article, Adult, cardiovascular risk, Adolescent, Birth weight, menarquia, Adipose tissue, Biology, 3121 Internal medicine, Research and Analysis Methods, medicine, overweight, Genetic Predisposition to Disease, Obesity, 030304 developmental biology, Waist-Hip Ratio, índice de masa corporal, Body Weight, Cardiometabolic Risk Factors, predisposición genética a la enfermedad, Heritability, Genome Analysis, young-adults, Genome-wide Association, índice cintura-cadera, Young-adults, genome-wide association, Genome-Wide Association Study
Abstract

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values, CP received funding from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. MMcC is a Wellcome Senior Investigator and an NIHR Senior Investigator. MMcC received funding from Wellcome (090532, 106130, 098381, 203141, 212259), NIDDK (U01DK105535), and NIHR (NF-SI-0617-10090). TGMV was supported by ZonMW (TOP 40-00812-9811010). DLC was supported by the American Diabetes Association Grant 1-17-PDF-077. SFAG is supported by the Daniel B. Burke Chair for Diabetes Research and NIH Grant R01 HD058886. NVT is funded by a pre-doctoral grant from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (2017 FI_B 00636), Generalitat de Catalunya -Fons Social Europeu. BK received personal funding from the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG -no. 322605). BF was supported by an Oak Foundation Fellowship. RMF and RNB are supported by Sir Henry Dale Fellowship (Wellcome Trust and Royal Society grant: WT104150). ATH is supported by a Wellcome Trust Senior Investigator award (grant number 098395/Z/12/Z). DM is supported by a Canada Research Chair. DLC was supported by the American Diabetes Association Grant 1-17-PDF077. JTL was supported by the Finnish Cultural Foundation. DIB received a KNAW Academy Professor Award (PAH/6635). MH received PhD scholarship funding from TARGET (http://target.ku.dk), The Danish Diabetes Academy (http://danishdiabetesacademy.dk) and the Copenhagen Graduate School of Health and Medical Sciences. VWVJ received funding from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (ERC-2014-CoG-648916). ISF was supported by the European Research Council, Wellcome Trust (098497/Z/12/Z), Medical Research Council (MRC_MC_UU_12012/5), the NIHR Cambridge Biomedical Research Centre, the Botnar Foundation, the Bernard Wolfe Health Neuroscience Endowment and the European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO n degrees 279153. IB acknowledges funding from Wellcome (WT206194). ES works in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1). KC received funds from the French National Agency of Research, F-CRIN/FORCE. All funding for the studies that provided the underlying data for this manuscript can be found in S1 Text. The funders had no role in study design, data collection and analysis, data interpretation, decision to publish, or preparation of the manuscript.

Published
2020
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10. Infant breastfeeding and childhood general, visceral, liver, and pericardial fat measures assessed by magnetic resonance imaging

Author

Janine F. Felix, Aad van der Lugt, Vincent W. V. Jaddoe, Liesbeth Duijts, Suzanne Vogelezang, Eline M. van der Beek, Susana Santos, Marieke Abrahamse-Berkeveld, Epidemiology, Erasmus MC other, Pediatrics, Radiology & Nuclear Medicine, Center for Liver, Digestive and Metabolic Diseases (CLDM), and Reproductive Origins of Adult Health and Disease (ROAHD)

Subjects
Male, obesity, breastfeeding, Breastfeeding, Medicine (miscellaneous), Physiology, 0302 clinical medicine, Surveys and Questionnaires, Abdomen, Mass index, Prospective Studies, 030212 general & internal medicine, Child, Infant Nutritional Physiological Phenomena, Prospective cohort study, 2. Zero hunger, adiposity, education.field_of_study, Nutrition and Dietetics, Body Fluid Compartments, X-RAY ABSORPTIOMETRY, ASSOCIATION, Magnetic Resonance Imaging, LARGE RANDOMIZED-TRIAL, Breast Feeding, ADIPOSE-TISSUE, Adipose Tissue, Liver, CARDIOVASCULAR-DISEASE, Female, Pericardium, infant feeding, visceral fat, Population, body mass index, 030209 endocrinology & metabolism, organ fat, Intra-Abdominal Fat, Childhood obesity, 03 medical and health sciences, medicine, Humans, education, childhood, business.industry, Infant, Newborn, Infant, SCHOOL-AGE-CHILDREN, medicine.disease, Obesity, BODY-MASS INDEX, ABDOMINAL FAT, RISK-FACTORS, business, Breast feeding, Body mass index
Abstract

Background: Although a longer duration of breastfeeding has been associated with a lower risk of childhood obesity, the impact on specific organ fat depots is largely unknown.Objective: We examined the associations of any breastfeeding, duration and exclusiveness of breastfeeding, and of age at introduction of solid foods with measures of general, visceral, and organ adiposity at 10 y.Design: In a population-based prospective cohort study in 4444 children, we obtained information on infant feeding by questionnaires. At the mean age of 9.8 y, we estimated body mass index from height and weight; fat mass index and fat-free mass index by dual-energy X-ray absorptiometry; and visceral fat index, pericardial fat index, and liver fat fraction by MRI. MRI scans were performed in a subgroup of 2646 children.Results: After adjustment for age and sex, we observed associations of infant feeding with all general, visceral, and organ fat outcomes, except for pericardial fat index, at the age of 10 y. After further adjustment for family-based sociodemographic, maternal lifestyle-related, and childhood factors, only the associations of shorter breastfeeding duration and nonexclusive breastfeeding with a lower fat-free mass index remained significant (P Conclusion: Our results suggest that the assoiations of any breastfeeding, duration and exclusiveness of breastfeeding, and age at the introduction of solid foods with general, visceral, and organ fat measures at the age of 10 y are largely explained by family-based sociodemographic factors.

Published
2018
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11. A trans-ancestral meta-analysis of Genome-wide Association Studies reveals loci associated with childhood obesity

Author

Jaakko T. Leinonen, Nicholas J. Timpson, Mohammad Hadi Zafarmand, Mette Hollensted, Anne E. Justice, Robert L. Hanson, Struan F.A. Grant, Frank D. Gilliland, Jesús Peralta-Romero, Diana L. Cousminer, Carol A. Wang, Jens-Christian Holm, Lindsay Fernández-Rhodes, Elina Hyppönen, Marc Vaudel, Marjo-Riitta Järvelin, Amélie Bonnefond, Esteban J. Parra, Robert I. Berkowitz, Koon K. Teo, Adnan Custovic, Christian Theil Have, Mariona Bustamante, Kari E. North, Stefan Johansson, Mustafa Atalay, Christine Frithioff-Bøjsøe, Estela Blanco, Adan Valladares-Salgado, Sylvain Sebert, Suzanne Vogelezang, Yujie Wang, Mark I. McCarthy, Timo A. Lakka, Christine Power, Raimo Joro, Oluf Pedersen, Heather M. Highland, Yik Ying Teo, Zhanghua Chen, Pål R. Njølstad, Momoko Horikoshi, William J. Gauderman, Øyvind Helgeland, Klaus Bønnelykke, Anke Hinney, Natalia Vilor-Tejedor, V. Saroja Voruganti, Niels Grarup, Sayuko Kobes, Shana E. McCormack, Christopher D. Brown, Alessandra Chesi, Nancy F. Butte, Triinu Peters, Miguel Cruz, Johan G. Eriksson, Torben Hansen, Babette S. Zemel, Terho Lehtimäki, Niina Pitkänen, Akram Alyass, Vincent W. V. Jaddoe, Elisabeth Thiering, Jonathan P. Bradfield, Eileen Tai-Hui Boh, Janine F. Felix, Olli T. Raitakari, Philippe Froguel, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Martine Vrijheid, Ville Karhunen, Mika Kähönen, Marie Standl, Angela Simpson, Seang-Mei Saw, David Meyre, Anthony G. Comuzzie, Mickaël Canouil, Tarunveer S. Ahluwalia, John A. Curtin, Barbera D. C. van Schaik, Johannes Hebebrand, Elisabeth Widen, Tanja G. M. Vrijkotte, Leslie J. Baier, Sheila Gahagan, Joachim Heinrich, Claire Monnereau, Jesús Vioque, Hans Bisgaard, Hakon Hakonarson, Estelle Lowry, Craig E. Pennell, Shelley A. Cole, Thorkild I. A. Sørensen, André G. Uitterlinden, Virpi Lindi, Genomics of Sex Differences, Institute for Molecular Medicine Finland, University of Helsinki, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Centre of Excellence in Complex Disease Genetics, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Bradfield, Jonathan P., Vogelezang, Suzanne, Felix, Janine F., Chesi, Alessandra, Hyppönen, Elina, Jaddoe, Vincent W.V., Early Growth Genetics Consortium, Epidemiology and Data Science, Public and occupational health, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, APH - Global Health, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, ARD - Amsterdam Reproduction and Development, APH - Methodology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Male, obesity, Pediatric Obesity, Medizin, IDENTIFIES 3, Genome-wide association study, VARIANTS, ethnic group, single nucleotide polymorphism, genetics, bayesian analysis, genes, Association Studies Article, Child, Genetics (clinical), 11 Medical and Health Sciences, 2. Zero hunger, Genetics, Genetics & Heredity, child, 0303 health sciences, adult, 030305 genetics & heredity, 1184 Genetics, developmental biology, physiology, Chromosome Mapping, General Medicine, 3. Good health, Female, body mass index procedure, childhood obesity, Life Sciences & Biomedicine, asian, Biochemistry & Molecular Biology, SUSCEPTIBILITY LOCI, DATABASE, Single-nucleotide polymorphism, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Wilms Tumor, Childhood obesity, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, MANAGEMENT, Humans, Genetic Predisposition to Disease, genome, Molecular Biology, 030304 developmental biology, genome-wide association study, Science & Technology, Early Growth Genetics Consortium, Case-control study, Bayes Theorem, 06 Biological Sciences, medicine.disease, Obesity, MC3R GENE, Genetic Loci, Case-Control Studies, 1182 Biochemistry, cell and molecular biology, Body mass index, Genome-Wide Association Study
Abstract

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2–18 years old) and 15 599 controls (consistently

Published
2019
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12. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Author

Tobias Hermle, Holger Kirsten, Karsten B. Sieber, Aiko P. J. de Vries, Su Chi Lim, Peter Kovacs, Charumathi Sabanayagam, Carl D. Langefeld, Bernhard K. Krämer, Kent D. Taylor, Janine F. Felix, Belen Ponte, Markus Loeffler, Mary F. Feitosa, Kai-Uwe Eckardt, Jianjun Liu, Katalin Dittrich, Charlene A. Wong, Uwe Völker, Adriana M. Hung, Thomas Meitinger, Anubha Mahajan, Anselm Hoppmann, Erik Ingelsson, Martin H. de Borst, Oscar H. Franco, Niek Verweij, Kai-Uwe Saum, Vilmundur Gudnason, Bram P. Prins, Carsten A. Böger, Terho Lehtimäki, Andrew A. Hicks, Todd L. Edwards, Olivier Devuyst, Peter P. Pramstaller, Katrin Horn, Leslie A. Lange, Johanne Tremblay, Jin-Fang Chai, Sahar Ghasemi, Kjell Nikus, Tanja Poulain, Massimiliano Cocca, Anna Köttgen, Eric Boerwinkle, Barry I. Freedman, Miao-Ling Chee, Man Li, Stephan J. L. Bakker, Tamara B. Harris, Albert V. Smith, Ton J. Rabelink, Dennis O. Mook-Kanamori, Iris M. Heid, Jasmin Divers, Chaolong Wang, Kathleen A. Ryan, Pavel Hamet, Silke Szymczak, Shih-Jen Hwang, Hauke Thomsen, Rainer Rettig, Ayush Giri, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Cristian Pattaro, Andrej Teren, Valencia Hui Xian Foo, Myriam Rheinberger, Audrey Y. Chu, Barbara McMullen, Franziska Grundner-Culemann, Masayuki Yasuda, Murielle Bochud, Martin Gögele, Anke Tönjes, Jeannette Lee, Adrienne Tin, Kevin Ho, Konstantin Strauch, Josef Coresh, Renée de Mutsert, Sandra Freitag-Wolf, Gardar Sveinbjornsson, Yizhe Xu, Katalin Susztak, Tien Yin Wong, Mary L. Biggs, Isleifur Olafsson, Qiong Yang, Antje Körner, Chengxiang Qiu, E-Shyong Tai, Martina Müller-Nurasyid, Ben Schöttker, Jeffrey O' Connell, Mengmeng Chen, Daniel F. Gudbjartsson, Dermot F. Reilly, Vincent W. V. Jaddoe, Damia Noce, Pim van der Harst, Sanaz Sedaghat, Chiea Chuen Khor, Adam S. Butterworth, Mathias Gorski, Robert J. Carroll, James G. Wilson, Johan Ärnlöv, Christa Meisinger, Kenneth Rice, Bettina Jung, Christian M. Shaffer, Unnur Thorsteinsdottir, Matthias Nauck, Shreeram Akilesh, Mika Kähönen, Johanna Jakobsdottir, Melanie Waldenberger, Ralph Burkhardt, Daniela Baptista, John Danesh, Benjamin B. Sun, Karlhans Endlich, Holly Kramer, Frauke Degenhardt, Wolfgang Lieb, Kari Stefansson, Joachim Thiery, Lars Lind, Nicholette D. Palmer, Sarah A. Pendergrass, Suzanne Vogelezang, Peter J. van der Most, Afshin Parsa, Markus Scholz, Florian Kronenberg, Joseph C. Maranville, Laura M. Raffield, Hermann Brenner, Wieland Kiess, Anna I. Podgornaia, Yuan Shi, Tanguy Corre, Miao-Li Chee, Deborah Mascalzoni, Bamidele O. Tayo, Navya Shilpa Josyula, Ching-Yu Cheng, Lea Gerstner, Nisha Bansal, Jerome I. Rotter, Alexander Teumer, Vilmantas Giedraitis, Raymond Noordam, Ron T. Gansevoort, Lihua Wang, Andrew P. Morris, Bruce M. Psaty, Boting Ning, Zhi Yu, Christian Fuchsberger, Matthias Wuttke, Heiko Runz, Annette Peters, Yih Chung Tham, James P. Cook, Yong Li, Chris H. L. Thio, Hilma Holm, Alessandro De Grandi, Jonathan Marten, André G. Uitterlinden, Andre Franke, Nicholas Y. Q. Tan, Otis D. Wilson, Georg Ehret, Cecilia M. Lindgren, Josyf C. Mychaleckyj, Wolfgang Koenig, Harold Snieder, Michael Stumvoll, Kozeta Miliku, M. Arfan Ikram, Teresa Nutile, Læknadeild (HÍ), Faculty of Medicine (UI), School of Health Sciences (UI), Heilbrigðisvísindasvið (HÍ), Háskóli Íslands, University of Iceland, Teumer, Alexander [0000-0002-8309-094X], Li, Yong [0000-0003-2651-8791], Wuttke, Matthias [0000-0003-3420-5082], Giri, Ayush [0000-0002-7786-4670], Qiu, Chengxiang [0000-0002-6346-8669], Kirsten, Holger [0000-0002-3126-7950], Tin, Adrienne [0000-0002-4207-5866], Feitosa, Mary F. [0000-0002-0933-2410], Chai, Jin-Fang [0000-0003-3770-1137], Cocca, Massimiliano [0000-0002-1127-7596], Gorski, Mathias [0000-0002-9103-5860], Horn, Katrin [0000-0002-5307-6936], Li, Man [0000-0002-3839-0281], Marten, Jonathan [0000-0001-6916-2014], van der Most, Peter J. [0000-0001-8450-3518], Burkhardt, Ralph [0000-0003-1924-1202], Coresh, Josef [0000-0002-4598-0669], de Borst, Martin H. [0000-0002-4127-8733], Ehret, Georg [0000-0002-5730-0675], Endlich, Karlhans [0000-0001-6052-6061], Felix, Janine F. [0000-0002-9801-5774], Franke, Andre [0000-0003-1530-5811], Freedman, Barry I. [0000-0003-0275-5530], Freitag-Wolf, Sandra [0000-0002-1069-7740], Giedraitis, Vilmantas [0000-0003-3423-2021], Grundner-Culemann, Franziska [0000-0001-9649-281X], Gudnason, Vilmundur [0000-0001-5696-0084], Hicks, Andrew A. [0000-0001-6320-0411], Ikram, M. Arfan [0000-0003-0372-8585], Ingelsson, Erik [0000-0003-2256-6972], Jaddoe, Vincent W. V. [0000-0003-2939-0041], Josyula, Navya Shilpa [0000-0003-2782-8812], Khor, Chiea-Chuen [0000-0002-1128-4729], Koenig, Wolfgang [0000-0002-2064-9603], Kovacs, Peter [0000-0002-0290-5423], Kronenberg, Florian [0000-0003-2229-1120], Lindgren, Cecilia M. [0000-0002-4903-9374], Liu, Jianjun [0000-0002-3255-3019], Lyytikäinen, Leo-Pekka [0000-0002-7200-5455], Mahajan, Anubha [0000-0001-5585-3420], Mascalzoni, Deborah [0000-0003-4156-1464], Miliku, Kozeta [0000-0002-9614-7191], Müller-Nurasyid, Martina [0000-0003-3793-5910], Mychaleckyj, Josyf C. [0000-0003-2595-0005], Palmer, Nicholette D. [0000-0001-8883-2511], Poulain, Tanja [0000-0003-3825-5829], Raffield, Laura M. [0000-0002-7892-193X], Rice, Kenneth M. [0000-0002-3071-7278], Rivadeneira, Fernando [0000-0001-9435-9441], Sabanayagam, Charumathi [0000-0002-4042-4719], Smith, Albert V. [0000-0003-1942-5845], Sun, Benjamin B. [0000-0001-6347-2281], Szymczak, Silke [0000-0002-8897-9035], Taylor, Kent D. [0000-0002-2756-4370], Thio, Chris H. L. [0000-0003-2623-7172], Uitterlinden, André G. [0000-0002-7276-3387], van der Harst, Pim [0000-0002-2713-686X], Verweij, Niek [0000-0002-4303-7685], Völker, Uwe [0000-0002-5689-3448], Wang, Chaolong [0000-0003-3945-1012], Yang, Qiong [0000-0002-3658-1375], Devuyst, Olivier [0000-0003-3744-4767], Edwards, Todd L. [0000-0003-4318-6119], Ho, Kevin [0000-0002-3054-8697], Morris, Andrew P. [0000-0002-6805-6014], Pendergrass, Sarah A. [0000-0002-0565-6522], Rotter, Jerome I. [0000-0001-7191-1723], Stefansson, Kari [0000-0003-1676-864X], Susztak, Katalin [0000-0002-1005-3726], Scholz, Markus [0000-0002-4059-1779], Butterworth, Adam S. [0000-0002-6915-9015], Hung, Adriana M. [0000-0002-3203-1608], Pattaro, Cristian [0000-0002-4119-0109], Köttgen, Anna [0000-0002-4671-3714], Apollo - University of Cambridge Repository, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Feitosa, Mary F [0000-0002-0933-2410], van der Most, Peter J [0000-0001-8450-3518], de Borst, Martin H [0000-0002-4127-8733], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Hicks, Andrew A [0000-0001-6320-0411], Ikram, M Arfan [0000-0003-0372-8585], Jaddoe, Vincent WV [0000-0003-2939-0041], Lindgren, Cecilia M [0000-0002-4903-9374], Mychaleckyj, Josyf C [0000-0003-2595-0005], Palmer, Nicholette D [0000-0001-8883-2511], Raffield, Laura M [0000-0002-7892-193X], Rice, Kenneth M [0000-0002-3071-7278], Smith, Albert V [0000-0003-1942-5845], Sun, Benjamin B [0000-0001-6347-2281], Taylor, Kent D [0000-0002-2756-4370], Thio, Chris HL [0000-0003-2623-7172], Uitterlinden, André G [0000-0002-7276-3387], Edwards, Todd L [0000-0003-4318-6119], Morris, Andrew P [0000-0002-6805-6014], Pendergrass, Sarah A [0000-0002-0565-6522], Rotter, Jerome I [0000-0001-7191-1723], Butterworth, Adam S [0000-0002-6915-9015], and Hung, Adriana M [0000-0002-3203-1608]

Subjects
0301 basic medicine, Drosophila melanogaster/genetics, Diabetes Mellitus/genetics, LD SCORE REGRESSION, 030232 urology & nephrology, 45/43, General Physics and Astronomy, Genome-wide association study, BLOOD-PRESSURE, Bioinformatics, GLOMERULAR-FILTRATION-RATE, Genome-wide association studies, Diabetes mellitus genetics, 0302 clinical medicine, Creatinine/urine, Risk Factors, Genome-wide, Phenomics, lcsh:Science, ddc:616, Regulation of gene expression, RISK, Gene knockdown, Kidney diseases, Multidisciplinary, HERITABILITY, Albuminuria/genetics, article, Chromosome Mapping, Kidney disease, ddc, 3. Good health, Drosophila melanogaster, Creatinine, Nýrnasjúkdómar, 692/4022/1585, Slit diaphragm, Medical genetics, medicine.symptom, Erfðarannsóknir, Medical Genetics, medicine.medical_specialty, Science, 631/208/205/2138, 610 Medicine & health, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Meta-Analysis as Topic, 360 Social problems & social services, Diabetes Mellitus, medicine, Animals, Humans, Albuminuria, Genetic Predisposition to Disease, ddc:610, EXCRETION RATE, CARDIOVASCULAR EVENTS, Genetic association, Medicinsk genetik, TRANS-EQTLS, KIDNEY-DISEASE, General Chemistry, 030104 developmental biology, Gene Expression Regulation, Genetic Loci, COLLABORATIVE METAANALYSIS, lcsh:Q, Genome-Wide Association Study
Abstract

Publisher's version (útgefin grein)., Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria., Competing interests: Karsten B. Sieber is full-time employee of GlaxoSmithKline. Gardar Sveinbjornsson, Daniel F. Gudbjartsson, Hilma Holm, Unnur Thorsteinsdottir and Kari Stefansson are full-time employees of deCODE genetics, Amgen Inc. John Danesh is member of the Novartis Cardiovascular and Metabolic Advisory Board, received grant support from Novartis. Oscar H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA. Wolfgang Koenig received modest consultation fees for advisory board meetings from Amgen, DalCor, Kowa, Novartis, Pfizer and Sanofi, and modest personal fees for lectures from Amgen, AstraZeneca, Novartis, Pfizer and Sanofi. Anna I. Podgornaia and Dermot F. Reilly are employees of Merck Sharp Dohme Corp., Whitehouse Station, NJ, USA. Kevin Ho disclosed a research and financial relationship with Sanofi-Genzyme. Bruce M. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Markus Scholz: Consultancy of and grant support from Merck Serono not related to this project. Adam S. Butterworth received grants from MSD, Pfizer, Novartis, Biogen and Bioverativ and personal fees from Novartis. Anna Köttgen received grant support from Gruenenthal not related to this project. The other authors declare no competing interests.

Published
2019
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13. Associations of Fetal and Infant Weight Change With General, Visceral, and Organ Adiposity at School Age

Author

Suzanne Vogelezang, Susana Santos, Liza Toemen, Janine F. Felix, Edwin H.G. Oei, Vincent W. V. Jaddoe, Epidemiology, Erasmus MC other, Pediatrics, and Radiology & Nuclear Medicine

Subjects
Adult, Male, medicine.medical_specialty, Population, 030209 endocrinology & metabolism, Weight Gain, Fetal Development, 03 medical and health sciences, Child Development, 0302 clinical medicine, Pregnancy, Birth Weight, Body Fat Distribution, Humans, Medicine, Mass index, Prospective Studies, 030212 general & internal medicine, Child, education, Adiposity, Netherlands, 2. Zero hunger, education.field_of_study, business.industry, Obstetrics, Weight change, Infant, Newborn, Infant, Gestational age, General Medicine, medicine.disease, Child, Preschool, Small for gestational age, Female, Generation R, Median body, business
Abstract

Importance Both fetal and infant growth influence obesity later in life. The association of longitudinal fetal and infant growth patterns with organ fat is unknown. Objective To examine the associations of fetal and infant weight change with general, visceral, and organ adiposity at school age. Design, Setting, and Participants This cohort study was embedded in the Generation R Study, a population-based prospective cohort study in Rotterdam, the Netherlands. Pregnant women with a delivery date between April 2002 and January 2006 were eligible to participate. Follow-up measurements were performed for 3205 children. Data analysis of this population was performed from July 26, 2018, to February 7, 2019. Exposures Fetal weight was estimated in the second and third trimester of pregnancy. Infant weight was measured at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in standard deviation scores greater than 0.67 between 2 ages. Main Outcomes and Measures Visceral fat index, pericardial fat index, and liver fat fraction were measured by magnetic resonance imaging. Results The sample consisted of 3205 children (1632 girls [50.9%]; mean [SD] age, 9.8 [0.3] years). Children born small for gestational age had the lowest median body mass index compared with children born appropriate for gestational age and large for gestational age (16.4 [90% range, 14.1-23.6] vs 16.9 [90% range, 14.4-22.8] vs 17.4 [90% range, 14.9-22.7]). Compared with children with normal fetal and infant growth (533 of 2370 [22.5%]), those with fetal weight deceleration followed by infant weight acceleration (263 of 2370 [11.1%]) had the highest visceral fat index (standard deviation scores, 0.18; 95% CI, 0.03-0.33;P = .02) and liver fat fraction (standard deviation scores, 0.34; 95% CI, 0.20-0.48;P Conclusions and Relevance Fetal and infant weight change patterns were both associated with childhood body fat, but weight change patterns in infancy tended to have larger effects. Fetal growth restriction followed by infant growth acceleration was associated with increased visceral and liver fat.

Published
2019

14. Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 are associated with gestational duration

Author

Bjarke Feenstra, Preben Bo Mortensen, Hakon Hakonarson, Carol A. Wang, Alfonso Buil, Ole Mors, Ron Nudel, Vincent W. V. Jaddoe, Matthew T. Weirauch, Ilkka Kalliala, Katja Pahkala, Elina Hyppönen, Frederick T.J. Lin, Jonathan P. Bradfield, Maria Carolina Borges, Frank Geller, Christine Power, Craig E. Pennell, Matthias Wielscher, Janine F. Felix, Denise M. Scholtens, Ge Zhang, Marjo-Riitta Järvelin, Andrew J. Schork, Wesley K. Thompson, David M. Hougaard, Daniel Miller, Line Skotte, Rachel M. Freathy, Mads Melbye, Shouneng Peng, Heather A. Boyd, Suzanne Vogelezang, João Fadista, Pål R. Njølstad, Bo Jacobsson, Merete Nordentoft, Xueping Liu, Leo-Pekka Lyytikäinen, Robert M. Rossi, Fernando Rivadeneira, Rebecca K. Vinding, Mary L. Marazita, M. Geoffrey Hayes, Ke Hao, Mariona Bustamante, Dorte Helenius, Tarunveer S. Ahluwalia, Jeffrey C. Murray, Kristin Skogstrand, Vivek Appadurai, Øyvind Helgeland, Bridget A. Knight, Robin N Beaumont, Thomas Werge, Klaus Bønnelykke, Mark I. McCarthy, Struan F.A. Grant, William L. Lowe, Hans Bisgaard, Bruce Bedell, Louis J. Muglia, Martine Vrijheid, Leah C. Kottyan, Stefan Johansson, Anders D. Børglum, Niina Pitkänen, Kelli K. Ryckman, Olli T. Raitakari, Xiaoting Chen, Jonas Bacelis, Debbie A Lawlor, Anubha Mahajan, and Julius Juodakis

Subjects
0303 health sciences, Fetus, Pregnancy, Physiology, Locus (genetics), Biology, medicine.disease, Genome, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Genotype, medicine, SNP, Gestation, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. We conducted a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 was associated with gestational duration; the association was replicated in 9,291 additional infants (combined P = 3.96 × 10−14). Analysis of 15,536 mother-child pairs showed that the association was driven by fetal rather than maternal genotype. Functional experiments showed that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

Published
2018
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15. Cross-sectional population associations between detailed adiposity measures and C-reactive protein levels at age 6 years: the Generation R Study

Author

Suzanne Vogelezang, Olta Gishti, Vincent W. V. Jaddoe, Janine F. Felix, Albert Hofman, Oscar H. Franco, Liza Toemen, Romy Gaillard, Epidemiology, and Erasmus MC other

Subjects
Male, medicine.medical_specialty, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Population, Abdominal Fat, Mothers, Medicine (miscellaneous), Genome-wide association study, Weight Gain, Polymorphism, Single Nucleotide, Waist–hip ratio, Risk Factors, Internal medicine, Body Fat Distribution, Humans, Medicine, Child, education, Adiposity, Netherlands, education.field_of_study, Nutrition and Dietetics, biology, Waist-Hip Ratio, business.industry, C-reactive protein, Genetic Variation, medicine.disease, Obesity, C-Reactive Protein, Cross-Sectional Studies, Endocrinology, biology.protein, Female, Generation R, business, Body mass index, Follow-Up Studies, Genome-Wide Association Study, Demography
Abstract

High body mass index is associated with increased C-reactive protein levels in childhood and adulthood. Little is known about the associations of detailed adiposity measures with C-reactive protein levels in childhood. We examined the associations of general and abdominal adiposity measures with C-reactive protein levels at school age. To gain insight into the direction of causality, we used genetic risk scores based on known genetic variants in adults as proxies for child adiposity measures and C-reactive protein levels.Within a population-based cohort study among 4338 children at the median age of 6.2 years, we measured body mass index, fat mass percentage, android/gynoid fat mass ratio and preperitoneal abdominal fat mass. We also measured C-reactive protein blood levels and defined increased levels as ⩾3.0 mg l(-1). Single-nucleotide polymorphisms (SNPs) for the weighted genetic risk scores were extracted from large genome-wide association studies on adult body mass index, waist-hip ratio and C-reactive protein levels.All fat mass measures were associated with increased C-reactive protein levels, even after adjusting for multiple confounders. Fat mass percentage was most strongly associated with increased C-reactive protein levels (odds ratio 1.46 (95% confidence interval 1.30-1.65) per increase standard deviation scores in fat mass percentage). The association was independent of body mass index. The genetic risk score based on adult body mass index SNPs, but not adult waist-hip ratio SNPs, tended to be associated with increased C-reactive protein levels at school age. The genetic risk score based on adult C-reactive protein level SNPs was not associated with adiposity measures at school age.Our results suggest that higher general and abdominal fat mass may lead to increased C-reactive protein levels at school age. Further studies are needed to replicate these results and explore the causality and long-term consequences.

Published
2015

16. Associations of genetic risk scores based on adult adiposity pathways with childhood growth and adiposity measures

Author

Suzanne Vogelezang, Claire Monnereau, Claudia J. Kruithof, Janine F. Felix, Vincent W. V. Jaddoe, Epidemiology, Erasmus MC other, and Pediatrics

Subjects
Male, 0301 basic medicine, Genome-wide association study, Population, Biology, Pediatrics, Energy homeostasis, 03 medical and health sciences, Child Development, 0302 clinical medicine, Genetics, Humans, Glucose homeostasis, Genetic Predisposition to Disease, Genetics(clinical), Obesity, 030212 general & internal medicine, Child, education, Prospective cohort study, Genetics (clinical), Body mass index, Adiposity, Netherlands, Genetic association, 2. Zero hunger, education.field_of_study, Framingham Risk Score, Infant, Overweight, 030104 developmental biology, Polymorphism, single nucleotide, Female, Metabolic Networks and Pathways, Research Article
Abstract

Background Results from genome-wide association studies (GWAS) identified many loci and biological pathways that influence adult body mass index (BMI). We aimed to identify if biological pathways related to adult BMI also affect infant growth and childhood adiposity measures. Methods We used data from a population-based prospective cohort study among 3,975 children with a mean age of 6 years. Genetic risk scores were constructed based on the 97 SNPs associated with adult BMI previously identified with GWAS and on 28 BMI related biological pathways based on subsets of these 97 SNPs. Outcomes were infant peak weight velocity, BMI at adiposity peak and age at adiposity peak, and childhood BMI, total fat mass percentage, android/gynoid fat ratio, and preperitoneal fat area. Analyses were performed using linear regression models. Results A higher overall adult BMI risk score was associated with infant BMI at adiposity peak and childhood BMI, total fat mass, android/gynoid fat ratio, and preperitoneal fat area (all p-values

Published
2016

17. Influence of common genetic variants on childhood kidney outcomes

Author

Janine F. Felix, Suzanne Vogelezang, Vincent W. V. Jaddoe, Oscar H. Franco, Kozeta Miliku, Albert Hofman, Epidemiology, Erasmus MC other, and Pediatrics

Subjects
0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, Population, 030232 urology & nephrology, Renal function, Kidney Volume, Kidney, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, Ethnicity, Medicine, Albuminuria, Humans, Prospective Studies, education, Child, Alleles, Subclinical infection, education.field_of_study, Creatinine, urogenital system, business.industry, Genetic Variation, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, chemistry, Child, Preschool, Pediatrics, Perinatology and Child Health, Regression Analysis, Microalbuminuria, Female, Kidney Diseases, business, Kidney disease, Genome-Wide Association Study, Glomerular Filtration Rate
Abstract

BACKGROUND Kidney measures in early life are associated with kidney disease in later life. We hypothesized that these associations are partly explained by common genetic variants that lead to both smaller kidneys with lower kidney function in early childhood and kidney disease in adulthood. METHODS We examined in a population-based prospective cohort study among 4,119 children the associations of a weighted genetic risk score combining 20 previously identified common genetic variants related to adult eGFRcreat with kidney outcomes in children aged 6.0 years (95% range 5.7-7.8). Childhood kidney outcomes included combined kidney volume, glomerular filtration rate (eGFR) based on creatinine levels, and microalbuminuria based on albumin and creatinine urine levels. RESULTS We observed that the genetic risk score based on variants related to impaired kidney function in adults was associated with a smaller combined kidney volume (P value 3.0 × 10(-3)) and with a lower eGFR (P value 4.0 × 10(-4)) in children. The genetic risk score was not associated with microalbuminuria. CONCLUSION Common genetic variants related to impaired kidney function in adults already lead to subclinical changes in childhood kidney outcomes. The well-known associations of kidney measures in early life with kidney disease in later life may at least be partly explained by common genetic variants.

Published
2016

18. Tracking of abdominal subcutaneous and preperitoneal fat mass during childhood. The Generation R Study

Author

Vincent W. V. Jaddoe, E.M. van der Beek, A. Hofman, Janine F. Felix, Romy Gaillard, Suzanne Vogelezang, Olta Gishti, M Abrahamse-Berkeveld, Epidemiology, Erasmus MC other, Pediatrics, and Pediatric Surgery

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Preperitoneal fat, Abdominal Fat, Subcutaneous Fat, Medicine (miscellaneous), 030209 endocrinology & metabolism, Intra-Abdominal Fat, Weight Gain, 03 medical and health sciences, 0302 clinical medicine, Medicine, Body Fat Distribution, Humans, 030212 general & internal medicine, Obesity, Prospective Studies, Prospective cohort study, Child, Body fat distribution, Adiposity, Netherlands, Ultrasonography, Nutrition and Dietetics, business.industry, Follow up studies, Health Surveys, Child, Preschool, Generation R, Female, Radiology, medicine.symptom, business, Weight gain, Follow-Up Studies
Abstract

Overweight and obesity in early life tends to track into later life. Not much is known about tracking of abdominal fat. Our objective was to examine the extent of tracking of abdominal fat measures during the first six years of life.We performed a prospective cohort study among 393 Dutch children followed from the age of 2 years (90% range 1.9; 2.3) until the age of 6 years (90% range 5.7; 6.2). At both ages, we performed abdominal ultrasound to measure abdominal subcutaneous and preperitoneal fat distances and areas, and we calculated the preperitoneal/subcutaneous fat distance ratio. High abdominal fat measures were defined as values in the upper 15%.Abdominal subcutaneous fat distance and area, and preperitoneal fat area at 2 years were correlated with their corresponding measures at 6 years (all P-values0.01), with the strongest coefficients for abdominal subcutaneous fat measures. Preperitoneal fat distance at the age of 2 years was not correlated with the corresponding measure at 6 years. The tracking coefficient for preperitoneal/subcutaneous fat distance ratio from 2 to 6 years was r=0.36 (P0.01). Children with high abdominal subcutaneous fat measures at 2 years had increased risk of having high abdominal subcutaneous fat measures at 6 years (odds ratios 9.2 (95% confidence interval (CI) 4.1-20.8) and 12.4 (95% CI 5.4-28.6) for subcutaneous fat distance and area, respectively). These associations were not observed for preperitoneal fat measures.Our findings suggest that both abdominal subcutaneous and preperitoneal fat mass measures track during childhood, but with stronger tracking for abdominal subcutaneous fat measures. An adverse abdominal fat distribution in early life may have long-term consequences.

Published
2015

19. Adult adiposity susceptibility loci, early growth and general and abdominal fatness in childhood: the Generation R Study

Author

Carry M. Renders, Janine F. Felix, Claire Monnereau, Vincent W. V. Jaddoe, Romy Gaillard, Suzanne Vogelezang, Albert Hofman, Prevention and Public Health, EMGO+ - Lifestyle, Overweight and Diabetes, Epidemiology, and Erasmus MC other

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Cell Adhesion Molecules, Neuronal, Abdominal Fat, Medicine (miscellaneous), Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Genome-wide association study, Biology, GPI-Linked Proteins, Weight Gain, Polymorphism, Single Nucleotide, Body Mass Index, Waist–hip ratio, Child Development, Risk Factors, Internal medicine, medicine, Abdominal fat, Body Fat Distribution, Humans, Prospective Studies, Prospective cohort study, Child, Body fat distribution, Adiposity, Nutrition and Dietetics, Waist-Hip Ratio, Infant, Newborn, Infant, Membrane Proteins, Proteins, Endocrinology, Child, Preschool, Susceptibility locus, Generation R, Female, Disease Susceptibility, Body mass index, Genome-Wide Association Study
Abstract

Genome-wide association studies in adults have identified genetic loci associated with adiposity measures. Little is known about the effects of these loci on growth and body fat distribution from early childhood onwards.In a population-based prospective cohort study among 4144 children, we examined the associations of weighted risk scores combining 29 known genetic markers of adult body mass index (BMI) and 14 known genetic markers of adult waist-hip ratio (WHR) with peak weight velocity, peak height velocity, age at adiposity peak and BMI at adiposity peak in early infancy and additionally with BMI, total fat mass, android/gynoid fat ratio and preperitoneal fat area at the median age of 6.0 years (95% range 5.7, 7.8).A higher adult BMI genetic risk score was associated with a higher age at adiposity peak in infancy and a higher BMI, total fat mass, android/gynoid fat ratio and preperitoneal fat area in childhood (P=0.05, 1.5 × 10(-24), 3.6 × 10(-18), 4.0 × 10(-11) and 1.3 × 10(-5), respectively), with the strongest association for childhood BMI with a 0.04 higher s.d. score BMI (95% confidence interval 0.03, 0.05) per additional risk allele. A higher adult WHR genetic risk score was not associated with infant growth measures or childhood BMI and total fat mass, but was associated with childhood android/gynoid fat ratio and preperitoneal fat area (P0.05).Genetic variants associated with BMI and WHR in adults influence growth patterns and general and abdominal fat development from early childhood onwards.

Published
2015
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