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17 results on '"Kooijman, Marjolein N."'

1. Differences in birth weight between immigrants' and natives' children in Europe and Australia:a LifeCycle comparative observational cohort study

Author

Florian, Sandra, Ichou, Mathieu, Panico, Lidia, Pinel-Jacquemin, Stéphanie, Vrijkotte, Tanja G.M., Harskamp-van Ginkel, Margreet W., Huang, Rae Chi, Carson, Jennie, Rodriguez, Loreto Santa Marina, Subiza-Pérez, Mikel, Vrijheid, Martine, Fernández-Barrés, Sílvia, Yang, Tiffany C., Wright, John, Corpeleijn, Eva, Cardol, Marloes, Isaevska, Elena, Moccia, Chiara, Kooijman, Marjolein N., Voerman, Ellis, Jaddoe, Vincent, Welten, Marieke, Spada, Elena, Rebagliato, Marisa, Beneito, Andrea, Ronfani, Luca, Charles, Marie Aline, Florian, Sandra, Ichou, Mathieu, Panico, Lidia, Pinel-Jacquemin, Stéphanie, Vrijkotte, Tanja G.M., Harskamp-van Ginkel, Margreet W., Huang, Rae Chi, Carson, Jennie, Rodriguez, Loreto Santa Marina, Subiza-Pérez, Mikel, Vrijheid, Martine, Fernández-Barrés, Sílvia, Yang, Tiffany C., Wright, John, Corpeleijn, Eva, Cardol, Marloes, Isaevska, Elena, Moccia, Chiara, Kooijman, Marjolein N., Voerman, Ellis, Jaddoe, Vincent, Welten, Marieke, Spada, Elena, Rebagliato, Marisa, Beneito, Andrea, Ronfani, Luca, and Charles, Marie Aline

Abstract

OBJECTIVE: Research on adults has identified an immigrant health advantage, known as the 'immigrant health paradox', by which migrants exhibit better health outcomes than natives. Is this health advantage transferred from parents to children in the form of higher birth weight relative to children of natives? SETTING: Western Europe and Australia. PARTICIPANTS: We use data from nine birth cohorts participating in the LifeCycle Project, including five studies with large samples of immigrants' children: Etude Longitudinale Française depuis l'Enfance-France (N=12 494), the Raine Study-Australia (N=2283), Born in Bradford-UK (N=4132), Amsterdam Born Children and their Development study-Netherlands (N=4030) and the Generation R study-Netherlands (N=4877). We include male and female babies born to immigrant and native parents. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is birth weight measured in grams. Different specifications were tested: birth weight as a continuous variable including all births (DV1), the same variable but excluding babies born with over 4500 g (DV2), low birth weight as a 0-1 binary variable (1=birth weight below 2500 g) (DV3). Results using these three measures were similar, only results using DV1 are presented. Parental migration status is measured in four categories: both parents natives, both born abroad, only mother born abroad and only father born abroad. RESULTS: Two patterns in children's birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, p<0.10) and Australia (+40 g, p<0.10) and lower birth weight among children of immigrants in the UK (-82 g, p<0.05) and the Netherlands (-80 g and -73 g, p<0.001) compared with natives' children. Smoking during pregnancy emerged as a mechanism explaining some of the birth weight gaps between children of immigrants and natives. CONCLUSION: The immigrant health advantage is not universally transferred to children

Published
2023

2. Differences in birth weight between immigrants' and natives' children in Europe and Australia: A LifeCycle comparative observational cohort study

Author

Florian, Sandra, Ichou, Mathieu, Panico, Lidia, Pinel-Jacquemin, Stéphanie, Vrijkotte, Tanja G. M., Harskamp-Van Ginkel, Margreet W., Huang, Rae-Chi, Carson, Jennie, Rodriguez, Loreto Santa Marina, Subiza-Pérez, Mikel, Vrijheid, Martine, Fernández-Barrés, Sílvia, Yang, Tiffany C., Wright, John, Corpeleijn, Eva, Cardol, Marloes, Isaevska, Elena, Moccia, Chiara, Kooijman, Marjolein N., Voerman, Ellis, Jaddoe, Vincent, Welten, Marieke, Spada, Elena, Rebagliato, Marisa, Beneito, Andrea, Ronfani, Luca, Charles, Marie-Aline, Florian, Sandra, Ichou, Mathieu, Panico, Lidia, Pinel-Jacquemin, Stéphanie, Vrijkotte, Tanja G. M., Harskamp-Van Ginkel, Margreet W., Huang, Rae-Chi, Carson, Jennie, Rodriguez, Loreto Santa Marina, Subiza-Pérez, Mikel, Vrijheid, Martine, Fernández-Barrés, Sílvia, Yang, Tiffany C., Wright, John, Corpeleijn, Eva, Cardol, Marloes, Isaevska, Elena, Moccia, Chiara, Kooijman, Marjolein N., Voerman, Ellis, Jaddoe, Vincent, Welten, Marieke, Spada, Elena, Rebagliato, Marisa, Beneito, Andrea, Ronfani, Luca, and Charles, Marie-Aline

Abstract

Objective: Research on adults has identified an immigrant health advantage, known as the 'immigrant health paradox', by which migrants exhibit better health outcomes than natives. Is this health advantage transferred from parents to children in the form of higher birth weight relative to children of natives? Setting: Western Europe and Australia. Participants: We use data from nine birth cohorts participating in the LifeCycle Project, including five studies with large samples of immigrants' children: Etude Longitudinale Française depuis l'Enfance - France (N=12 494), the Raine Study - Australia (N=2283), Born in Bradford - UK (N=4132), Amsterdam Born Children and their Development study - Netherlands (N=4030) and the Generation R study - Netherlands (N=4877). We include male and female babies born to immigrant and native parents. Primary and secondary outcome measures: The primary outcome is birth weight measured in grams. Different specifications were tested: birth weight as a continuous variable including all births (DV1), the same variable but excluding babies born with over 4500 g (DV2), low birth weight as a 0-1 binary variable (1=birth weight below 2500 g) (DV3). Results using these three measures were similar, only results using DV1 are presented. Parental migration status is measured in four categories: both parents natives, both born abroad, only mother born abroad and only father born abroad. Results: Two patterns in children's birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, p < 0.10) and Australia (+40 g, p < 0.10) and lower birth weight among children of immigrants in the UK (-82 g, p < 0.05) and the Netherlands (-80 g and -73 g, p < 0.001) compared with natives' children. Smoking during pregnancy emerged as a mechanism explaining some of the birth weight gaps between children of immigrants and natives. Conclusion: The immigrant health advantage is not universally transferred to childr

Published
2023

3. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

Author

Warrington, Nicole M, Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, EGG Consortium, Morgen, Camilla S, van Kampen, Antoine HC, van Schaik, Barbera DC, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil VR, Fonvig, Cilius E, Warrington, Nicole M, Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, EGG Consortium, Morgen, Camilla S, van Kampen, Antoine HC, van Schaik, Barbera DC, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil VR, and Fonvig, Cilius E

Abstract

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.

Published
2019

4. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Author

Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia Jue Johannes, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Consortium, EGG, Morgen, Camilla S, van Kampen, Antoine H C, van Schaik, Barbera D C, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil V R, Fonvig, Cilius E, Trier, Caecilie, van Beijsterveldt, Catharina E M, Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M, Mercader, Josep M, Linneberg, Allan, Schraut, Katharina E, Lind, Penelope A, Medland, Sarah E, Shields, Beverley M, Knight, Bridget A, Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K, Willems, Sara M, Atalay, Mustafa, Chawes, Bo L, Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A, Yaghootkar, Hanieh, Ruth, Katherine S, Jones, Samuel E, Loh, Po-Ru, Murray, Anna, Weedon, Michael N, Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F, Eloranta, Aino-Maija, Lakka, Timo A, van Duijn, Cornelia M, Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T, Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V, Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W, Campbell, Harry, Wilson, James F, Vrijkotte, Tanja G M, Vrijheid, Martine, de Geus, Eco J C N, Hayes, M Geoffrey, Kadarmideen, Haja N, Holm, Jens-Christian, Beilin, Lawrence J, Pennell, Craig E, Heinrich, Joachim, Adair, Linda S, Borja, Judith B, Mohlke, Karen L, Eriksson, Johan G, Widén, Elisabeth E, Hattersley, Andrew T, Spector, Tim D, Kähönen, Mika, Viikari, Jorma S, Lehtimäki, Terho, Boomsma, Dorret I, Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild I A, Bisgaard, Hans Flinker, Bønnelykke, Klaus, Murray, Jeffrey C, Melbye, Mads, Nohr, Ellen A, Mook-Kanamori, Dennis O, Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F, Jaddoe, Vincent W V, Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A, Pedersen, Oluf, Uitterlinden, André G, Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M, Lowe, William L, Davey Smith, George, Timpson, Nicholas J, Morris, Andrew P, Wareham, Nicholas J, Hakonarson, Hakon, Grant, Struan F A, Frayling, Timothy M, Lawlor, Debbie A, Njølstad, Pål R, Johansson, Stefan, Ong, Ken K, McCarthy, Mark I, Perry, John R B, Evans, David M, Freathy, Rachel M, Warrington, Nicole M, Beaumont, Robin N, Horikoshi, Momoko, Day, Felix R, Helgeland, Øyvind, Laurin, Charles, Bacelis, Jonas, Peng, Shouneng, Hao, Ke, Feenstra, Bjarke, Wood, Andrew R, Mahajan, Anubha, Tyrrell, Jessica, Robertson, Neil R, Rayner, N William, Qiao, Zhen, Moen, Gunn-Helen, Vaudel, Marc, Marsit, Carmen J, Chen, Jia Jue Johannes, Nodzenski, Michael, Schnurr, Theresia M, Zafarmand, Mohammad H, Bradfield, Jonathan P, Grarup, Niels, Kooijman, Marjolein N, Li-Gao, Ruifang, Geller, Frank, Ahluwalia, Tarunveer S, Paternoster, Lavinia, Rueedi, Rico, Huikari, Ville, Hottenga, Jouke-Jan, Lyytikäinen, Leo-Pekka, Cavadino, Alana, Metrustry, Sarah, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Vilor-Tejedor, Natalia, Joshi, Peter K, Painter, Jodie N, Ntalla, Ioanna, Myhre, Ronny, Pitkänen, Niina, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Richmond, Rebecca C, Espinosa, Ana, Barton, Sheila J, Inskip, Hazel M, Holloway, John W, Santa-Marina, Loreto, Estivill, Xavier, Ang, Wei, Marsh, Julie A, Reichetzeder, Christoph, Marullo, Letizia, Hocher, Berthold, Lunetta, Kathryn L, Murabito, Joanne M, Relton, Caroline L, Kogevinas, Manolis, Chatzi, Leda, Allard, Catherine, Bouchard, Luigi, Hivert, Marie-France, Zhang, Ge, Muglia, Louis J, Heikkinen, Jani, Consortium, EGG, Morgen, Camilla S, van Kampen, Antoine H C, van Schaik, Barbera D C, Mentch, Frank D, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Hemani, Gibran, Ring, Susan M, Bennett, Amanda J, Gaulton, Kyle J, Fernandez-Tajes, Juan, van Zuydam, Natalie R, Medina-Gomez, Carolina, de Haan, Hugoline G, Rosendaal, Frits R, Kutalik, Zoltán, Marques-Vidal, Pedro, Das, Shikta, Willemsen, Gonneke, Mbarek, Hamdi, Müller-Nurasyid, Martina, Standl, Marie, Appel, Emil V R, Fonvig, Cilius E, Trier, Caecilie, van Beijsterveldt, Catharina E M, Murcia, Mario, Bustamante, Mariona, Bonas-Guarch, Sílvia, Hougaard, David M, Mercader, Josep M, Linneberg, Allan, Schraut, Katharina E, Lind, Penelope A, Medland, Sarah E, Shields, Beverley M, Knight, Bridget A, Chai, Jin-Fang, Panoutsopoulou, Kalliope, Bartels, Meike, Sánchez, Friman, Stokholm, Jakob, Torrents, David, Vinding, Rebecca K, Willems, Sara M, Atalay, Mustafa, Chawes, Bo L, Kovacs, Peter, Prokopenko, Inga, Tuke, Marcus A, Yaghootkar, Hanieh, Ruth, Katherine S, Jones, Samuel E, Loh, Po-Ru, Murray, Anna, Weedon, Michael N, Tönjes, Anke, Stumvoll, Michael, Michaelsen, Kim F, Eloranta, Aino-Maija, Lakka, Timo A, van Duijn, Cornelia M, Kiess, Wieland, Körner, Antje, Niinikoski, Harri, Pahkala, Katja, Raitakari, Olli T, Jacobsson, Bo, Zeggini, Eleftheria, Dedoussis, George V, Teo, Yik-Ying, Saw, Seang-Mei, Montgomery, Grant W, Campbell, Harry, Wilson, James F, Vrijkotte, Tanja G M, Vrijheid, Martine, de Geus, Eco J C N, Hayes, M Geoffrey, Kadarmideen, Haja N, Holm, Jens-Christian, Beilin, Lawrence J, Pennell, Craig E, Heinrich, Joachim, Adair, Linda S, Borja, Judith B, Mohlke, Karen L, Eriksson, Johan G, Widén, Elisabeth E, Hattersley, Andrew T, Spector, Tim D, Kähönen, Mika, Viikari, Jorma S, Lehtimäki, Terho, Boomsma, Dorret I, Sebert, Sylvain, Vollenweider, Peter, Sørensen, Thorkild I A, Bisgaard, Hans Flinker, Bønnelykke, Klaus, Murray, Jeffrey C, Melbye, Mads, Nohr, Ellen A, Mook-Kanamori, Dennis O, Rivadeneira, Fernando, Hofman, Albert, Felix, Janine F, Jaddoe, Vincent W V, Hansen, Torben, Pisinger, Charlotta, Vaag, Allan A, Pedersen, Oluf, Uitterlinden, André G, Järvelin, Marjo-Riitta, Power, Christine, Hyppönen, Elina, Scholtens, Denise M, Lowe, William L, Davey Smith, George, Timpson, Nicholas J, Morris, Andrew P, Wareham, Nicholas J, Hakonarson, Hakon, Grant, Struan F A, Frayling, Timothy M, Lawlor, Debbie A, Njølstad, Pål R, Johansson, Stefan, Ong, Ken K, McCarthy, Mark I, Perry, John R B, Evans, David M, and Freathy, Rachel M

Abstract

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.

Published
2019

5. Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

Author

Tachmazidou, Ioanna, Süveges, Dániel, Min, Josine L, Ritchie, Graham R S, Steinberg, Julia, Walter, Klaudia, Iotchkova, Valentina, Schwartzentruber, Jeremy, Huang, Jie, Memari, Yasin, McCarthy, Shane, Crawford, Andrew J., Bombieri, Cristina, Cocca, Massimiliano, Farmaki, Aliki-Eleni, Gaunt, Tom R, Jousilahti, Pekka, Kooijman, Marjolein N, Lehne, Benjamin, Malerba, Giovanni, Männistö, Satu, Matchan, Angela, Medina-Gomez, Carolina, Metrustry, Sarah J, Nag, Abhishek, Ntalla, Ioanna, Paternoster, Lavinia, Rayner, Nigel W, Sala, Cinzia, Scott, William R, Shihab, Hashem A., Southam, Lorraine, St Pourcain, Beate, Traglia, Michela, Trajanoska, Katerina, Zaza, Gialuigi, Zhang, Weihua, Artigas, Maria Soler, Bansal, Narinder, Benn, Marianne, Chen, Zhongsheng, Danecek, Petr, Lin, Wei-Yu, Locke, Adam E, Luan, Jian'an, Manning, Alisa K, Mulas, Antonella, Sidore, Carlo, Tybjaerg-Hansen, Anne, Nordestgaard, Børge G, Tachmazidou, Ioanna, Süveges, Dániel, Min, Josine L, Ritchie, Graham R S, Steinberg, Julia, Walter, Klaudia, Iotchkova, Valentina, Schwartzentruber, Jeremy, Huang, Jie, Memari, Yasin, McCarthy, Shane, Crawford, Andrew J., Bombieri, Cristina, Cocca, Massimiliano, Farmaki, Aliki-Eleni, Gaunt, Tom R, Jousilahti, Pekka, Kooijman, Marjolein N, Lehne, Benjamin, Malerba, Giovanni, Männistö, Satu, Matchan, Angela, Medina-Gomez, Carolina, Metrustry, Sarah J, Nag, Abhishek, Ntalla, Ioanna, Paternoster, Lavinia, Rayner, Nigel W, Sala, Cinzia, Scott, William R, Shihab, Hashem A., Southam, Lorraine, St Pourcain, Beate, Traglia, Michela, Trajanoska, Katerina, Zaza, Gialuigi, Zhang, Weihua, Artigas, Maria Soler, Bansal, Narinder, Benn, Marianne, Chen, Zhongsheng, Danecek, Petr, Lin, Wei-Yu, Locke, Adam E, Luan, Jian'an, Manning, Alisa K, Mulas, Antonella, Sidore, Carlo, Tybjaerg-Hansen, Anne, and Nordestgaard, Børge G

Abstract

Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.

Published
2017

6. Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

Author

Tachmazidou, Ioanna, Süveges, Dániel, Min, Josine L., Ritchie, Graham R. S., Steinberg, Julia, Walter, Klaudia, Iotchkova, Valentina, Schwartzentruber, Jeremy, Huang, Jie, Memari, Yasin, Mccarthy, Shane, Crawford, Andrew A., Bombieri, Cristina, Cocca, Massimiliano, Farmaki, Aliki-Eleni, Gaunt, Tom R., Jousilahti, Pekka, Kooijman, Marjolein N., Lehne, Benjamin, Malerba, Giovanni, Männistö, Satu, Matchan, Angela, Medina-Gomez, Carolina, Metrustry, Sarah J., Nag, Abhishek, Ntalla, Ioanna, Paternoster, Lavinia, Rayner, Nigel W., Sala, Cinzia, Scott, William R., Shihab, Hashem A., Southam, Lorraine, St Pourcain, Beate, Traglia, Michela, Trajanoska, Katerina, Zaza, Gialuigi, Zhang, Weihua, Artigas, María S., Bansal, Narinder, Benn, Marianne, Chen, Zhongsheng, Danecek, Petr, Lin, Wei-Yu, Locke, Adam, Luan, Jian'An, Manning, Alisa K., Mulas, Antonella, Sidore, Carlo, Tybjaerg-Hansen, Anne, Varbo, Anette, Zoledziewska, Magdalena, Finan, Chri, Hatzikotoulas, Konstantino, Hendricks, Audrey E., Kemp, John P., Moayyeri, Alireza, Panoutsopoulou, Kalliope, Szpak, Michal, Wilson, Scott G., Boehnke, Michael, Cucca, Francesco, Di Angelantonio, Emanuele, Langenberg, Claudia, Lindgren, Cecilia, Mccarthy, Mark I., Morris, Andrew P., Nordestgaard, Børge G., Scott, Robert A., Tobin, Martin D., Wareham, Nicholas J., Burton, Paul, Chambers, John C., Smith, George Davey, Dedoussis, George, Felix, Janine F., Franco, Oscar H., Gambaro, Giovanni, Gasparini, Paolo, Hammond, Christopher J., Hofman, Albert, Jaddoe, Vincent W. V., Kleber, Marcu, Kooner, Jaspal S., Perola, Marku, Relton, Caroline, Ring, Susan M., Rivadeneira, Fernando, Salomaa, Veikko, Spector, Timothy D., Stegle, Oliver, Toniolo, Daniela, Uitterlinden, André G., Barroso, Inê, Greenwood, Celia M. T., Perry, John R. B., Walker, Brian R., Butterworth, Adam S., Xue, Yali, Durbin, Richard, Small, Kerrin S., Soranzo, Nicole, Timpson, Nicholas J., Zeggini, Eleftheria, Gambaro, Giovanni (ORCID:0000-0001-5733-2370), Tachmazidou, Ioanna, Süveges, Dániel, Min, Josine L., Ritchie, Graham R. S., Steinberg, Julia, Walter, Klaudia, Iotchkova, Valentina, Schwartzentruber, Jeremy, Huang, Jie, Memari, Yasin, Mccarthy, Shane, Crawford, Andrew A., Bombieri, Cristina, Cocca, Massimiliano, Farmaki, Aliki-Eleni, Gaunt, Tom R., Jousilahti, Pekka, Kooijman, Marjolein N., Lehne, Benjamin, Malerba, Giovanni, Männistö, Satu, Matchan, Angela, Medina-Gomez, Carolina, Metrustry, Sarah J., Nag, Abhishek, Ntalla, Ioanna, Paternoster, Lavinia, Rayner, Nigel W., Sala, Cinzia, Scott, William R., Shihab, Hashem A., Southam, Lorraine, St Pourcain, Beate, Traglia, Michela, Trajanoska, Katerina, Zaza, Gialuigi, Zhang, Weihua, Artigas, María S., Bansal, Narinder, Benn, Marianne, Chen, Zhongsheng, Danecek, Petr, Lin, Wei-Yu, Locke, Adam, Luan, Jian'An, Manning, Alisa K., Mulas, Antonella, Sidore, Carlo, Tybjaerg-Hansen, Anne, Varbo, Anette, Zoledziewska, Magdalena, Finan, Chri, Hatzikotoulas, Konstantino, Hendricks, Audrey E., Kemp, John P., Moayyeri, Alireza, Panoutsopoulou, Kalliope, Szpak, Michal, Wilson, Scott G., Boehnke, Michael, Cucca, Francesco, Di Angelantonio, Emanuele, Langenberg, Claudia, Lindgren, Cecilia, Mccarthy, Mark I., Morris, Andrew P., Nordestgaard, Børge G., Scott, Robert A., Tobin, Martin D., Wareham, Nicholas J., Burton, Paul, Chambers, John C., Smith, George Davey, Dedoussis, George, Felix, Janine F., Franco, Oscar H., Gambaro, Giovanni, Gasparini, Paolo, Hammond, Christopher J., Hofman, Albert, Jaddoe, Vincent W. V., Kleber, Marcu, Kooner, Jaspal S., Perola, Marku, Relton, Caroline, Ring, Susan M., Rivadeneira, Fernando, Salomaa, Veikko, Spector, Timothy D., Stegle, Oliver, Toniolo, Daniela, Uitterlinden, André G., Barroso, Inê, Greenwood, Celia M. T., Perry, John R. B., Walker, Brian R., Butterworth, Adam S., Xue, Yali, Durbin, Richard, Small, Kerrin S., Soranzo, Nicole, Timpson, Nicholas J., Zeggini, Eleftheria, and Gambaro, Giovanni (ORCID:0000-0001-5733-2370)

Abstract

Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.

Published
2017

7. Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

Author

Tachmazidou, Ioanna, Süveges, Dániel, Min, Josine L, Ritchie, Graham R S, Steinberg, Julia, Walter, Klaudia, Iotchkova, Valentina, Schwartzentruber, Jeremy, Huang, Jie, Memari, Yasin, McCarthy, Shane, Crawford, Andrew J., Bombieri, Cristina, Cocca, Massimiliano, Farmaki, Aliki-Eleni, Gaunt, Tom R, Jousilahti, Pekka, Kooijman, Marjolein N, Lehne, Benjamin, Malerba, Giovanni, Männistö, Satu, Matchan, Angela, Medina-Gomez, Carolina, Metrustry, Sarah J, Nag, Abhishek, Ntalla, Ioanna, Paternoster, Lavinia, Rayner, Nigel W, Sala, Cinzia, Scott, William R, Shihab, Hashem A., Southam, Lorraine, St Pourcain, Beate, Traglia, Michela, Trajanoska, Katerina, Zaza, Gialuigi, Zhang, Weihua, Artigas, Maria Soler, Bansal, Narinder, Benn, Marianne, Chen, Zhongsheng, Danecek, Petr, Lin, Wei-Yu, Locke, Adam E, Luan, Jian'an, Manning, Alisa K, Mulas, Antonella, Sidore, Carlo, Tybjaerg-Hansen, Anne, Nordestgaard, Børge G, Tachmazidou, Ioanna, Süveges, Dániel, Min, Josine L, Ritchie, Graham R S, Steinberg, Julia, Walter, Klaudia, Iotchkova, Valentina, Schwartzentruber, Jeremy, Huang, Jie, Memari, Yasin, McCarthy, Shane, Crawford, Andrew J., Bombieri, Cristina, Cocca, Massimiliano, Farmaki, Aliki-Eleni, Gaunt, Tom R, Jousilahti, Pekka, Kooijman, Marjolein N, Lehne, Benjamin, Malerba, Giovanni, Männistö, Satu, Matchan, Angela, Medina-Gomez, Carolina, Metrustry, Sarah J, Nag, Abhishek, Ntalla, Ioanna, Paternoster, Lavinia, Rayner, Nigel W, Sala, Cinzia, Scott, William R, Shihab, Hashem A., Southam, Lorraine, St Pourcain, Beate, Traglia, Michela, Trajanoska, Katerina, Zaza, Gialuigi, Zhang, Weihua, Artigas, Maria Soler, Bansal, Narinder, Benn, Marianne, Chen, Zhongsheng, Danecek, Petr, Lin, Wei-Yu, Locke, Adam E, Luan, Jian'an, Manning, Alisa K, Mulas, Antonella, Sidore, Carlo, Tybjaerg-Hansen, Anne, and Nordestgaard, Børge G

Abstract

Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.

Published
2017

8. Genome-wide associations for birth weight and correlations with adult disease.

Author

Horikoshi, Momoko, Horikoshi, Momoko, Beaumont, Robin N, Day, Felix R, Warrington, Nicole M, Kooijman, Marjolein N, Fernandez-Tajes, Juan, Feenstra, Bjarke, van Zuydam, Natalie R, Gaulton, Kyle J, Grarup, Niels, Bradfield, Jonathan P, Strachan, David P, Li-Gao, Ruifang, Ahluwalia, Tarunveer S, Kreiner, Eskil, Rueedi, Rico, Lyytikäinen, Leo-Pekka, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Hottenga, Jouke-Jan, Vilor-Tejedor, Natalia, Joshi, Peter K, Boh, Eileen Tai Hui, Ntalla, Ioanna, Pitkänen, Niina, Mahajan, Anubha, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Nodzenski, Michael, Diver, Louise A, Zondervan, Krina T, Bustamante, Mariona, Marques-Vidal, Pedro, Mercader, Josep M, Bennett, Amanda J, Rahmioglu, Nilufer, Nyholt, Dale R, Ma, Ronald Ching Wan, Tam, Claudia Ha Ting, Tam, Wing Hung, CHARGE Consortium Hematology Working Group, Ganesh, Santhi K, van Rooij, Frank Ja, Jones, Samuel E, Loh, Po-Ru, Ruth, Katherine S, Tuke, Marcus A, Tyrrell, Jessica, Wood, Andrew R, Yaghootkar, Hanieh, Scholtens, Denise M, Paternoster, Lavinia, Prokopenko, Inga, Kovacs, Peter, Atalay, Mustafa, Willems, Sara M, Panoutsopoulou, Kalliope, Wang, Xu, Carstensen, Lisbeth, Geller, Frank, Schraut, Katharina E, Murcia, Mario, van Beijsterveldt, Catharina Em, Willemsen, Gonneke, Appel, Emil VR, Fonvig, Cilius E, Trier, Caecilie, Tiesler, Carla Mt, Standl, Marie, Kutalik, Zoltán, Bonas-Guarch, Sílvia, Hougaard, David M, Sánchez, Friman, Torrents, David, Waage, Johannes, Hollegaard, Mads V, de Haan, Hugoline G, Rosendaal, Frits R, Medina-Gomez, Carolina, Ring, Susan M, Hemani, Gibran, McMahon, George, Robertson, Neil R, Groves, Christopher J, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Mentch, Frank D, MacKenzie, Scott M, Reynolds, Rebecca M, Early Growth Genetics (EGG) Consortium, Lowe, William L, Tönjes, Anke, Stumvoll, Michael, Lindi, Virpi, Horikoshi, Momoko, Horikoshi, Momoko, Beaumont, Robin N, Day, Felix R, Warrington, Nicole M, Kooijman, Marjolein N, Fernandez-Tajes, Juan, Feenstra, Bjarke, van Zuydam, Natalie R, Gaulton, Kyle J, Grarup, Niels, Bradfield, Jonathan P, Strachan, David P, Li-Gao, Ruifang, Ahluwalia, Tarunveer S, Kreiner, Eskil, Rueedi, Rico, Lyytikäinen, Leo-Pekka, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Hottenga, Jouke-Jan, Vilor-Tejedor, Natalia, Joshi, Peter K, Boh, Eileen Tai Hui, Ntalla, Ioanna, Pitkänen, Niina, Mahajan, Anubha, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Nodzenski, Michael, Diver, Louise A, Zondervan, Krina T, Bustamante, Mariona, Marques-Vidal, Pedro, Mercader, Josep M, Bennett, Amanda J, Rahmioglu, Nilufer, Nyholt, Dale R, Ma, Ronald Ching Wan, Tam, Claudia Ha Ting, Tam, Wing Hung, CHARGE Consortium Hematology Working Group, Ganesh, Santhi K, van Rooij, Frank Ja, Jones, Samuel E, Loh, Po-Ru, Ruth, Katherine S, Tuke, Marcus A, Tyrrell, Jessica, Wood, Andrew R, Yaghootkar, Hanieh, Scholtens, Denise M, Paternoster, Lavinia, Prokopenko, Inga, Kovacs, Peter, Atalay, Mustafa, Willems, Sara M, Panoutsopoulou, Kalliope, Wang, Xu, Carstensen, Lisbeth, Geller, Frank, Schraut, Katharina E, Murcia, Mario, van Beijsterveldt, Catharina Em, Willemsen, Gonneke, Appel, Emil VR, Fonvig, Cilius E, Trier, Caecilie, Tiesler, Carla Mt, Standl, Marie, Kutalik, Zoltán, Bonas-Guarch, Sílvia, Hougaard, David M, Sánchez, Friman, Torrents, David, Waage, Johannes, Hollegaard, Mads V, de Haan, Hugoline G, Rosendaal, Frits R, Medina-Gomez, Carolina, Ring, Susan M, Hemani, Gibran, McMahon, George, Robertson, Neil R, Groves, Christopher J, Langenberg, Claudia, Luan, Jian'an, Scott, Robert A, Zhao, Jing Hua, Mentch, Frank D, MacKenzie, Scott M, Reynolds, Rebecca M, Early Growth Genetics (EGG) Consortium, Lowe, William L, Tönjes, Anke, Stumvoll, Michael, and Lindi, Virpi

Abstract

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10-8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 × 10-13), T2D (Rg = -0.27, P = 1.1 × 10-6) and coronary artery disease (Rg = -0.30, P = 6.5 × 10-9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10-4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

Published
2016

9. Genome-wide associations for birth weight and correlations with adult disease

Author

Horikoshi, Momoko, Beaumont, Robin N, Day, Felix R, Warrington, Nicole M, Kooijman, Marjolein N, Fernandez-Tajes, Juan, Feenstra, Bjarke, van Zuydam, Natalie R, Gaulton, Kyle J, Grarup, Niels, Bradfield, Jonathan P, Strachan, David P, Li-Gao, Ruifang, Ahluwalia, Tarun Veer Singh, Kreiner, Eskil, Rueedi, Rico, Lyytikäinen, Leo-Pekka, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Hottenga, Jouke-Jan, Vilor-Tejedor, Natalia, Joshi, Peter K, Boh, Eileen Tai Hui, Ntalla, Ioanna, Pitkänen, Niina, Mahajan, Anubha, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Nodzenski, Michael, Diver, Louise A, Zondervan, Krina T, Bustamante, Mariona, Marques-Vidal, Pedro, Mercader, Josep M, Appel, Emil V. R., Waage, Johannes, Sørensen, Thorkild I A, Melbye, Mads, Kadarmideen, Haja N, Holm, Jens-Christian, Hansen, Torben, Bønnelykke, Klaus, Bisgaard, Hans, Pisinger, Charlotta, Pedersen, Oluf, Vaag, Allan A, Horikoshi, Momoko, Beaumont, Robin N, Day, Felix R, Warrington, Nicole M, Kooijman, Marjolein N, Fernandez-Tajes, Juan, Feenstra, Bjarke, van Zuydam, Natalie R, Gaulton, Kyle J, Grarup, Niels, Bradfield, Jonathan P, Strachan, David P, Li-Gao, Ruifang, Ahluwalia, Tarun Veer Singh, Kreiner, Eskil, Rueedi, Rico, Lyytikäinen, Leo-Pekka, Cousminer, Diana L, Wu, Ying, Thiering, Elisabeth, Wang, Carol A, Have, Christian T, Hottenga, Jouke-Jan, Vilor-Tejedor, Natalia, Joshi, Peter K, Boh, Eileen Tai Hui, Ntalla, Ioanna, Pitkänen, Niina, Mahajan, Anubha, van Leeuwen, Elisabeth M, Joro, Raimo, Lagou, Vasiliki, Nodzenski, Michael, Diver, Louise A, Zondervan, Krina T, Bustamante, Mariona, Marques-Vidal, Pedro, Mercader, Josep M, Appel, Emil V. R., Waage, Johannes, Sørensen, Thorkild I A, Melbye, Mads, Kadarmideen, Haja N, Holm, Jens-Christian, Hansen, Torben, Bønnelykke, Klaus, Bisgaard, Hans, Pisinger, Charlotta, Pedersen, Oluf, and Vaag, Allan A

Abstract

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10(-8)). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 × 10(-13)), T2D (Rg = -0.27, P = 1.1 × 10(-6)) and coronary artery disease (Rg = -0.30, P = 6.5 × 10(-9)). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10(-4)). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

Published
2016

10. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J.P., Kreiner-Møller, Eskil, Kooijman, Marjolein N., Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P., Geller, Frank, Hayes, M. Geoffrey, Cousminer, Diana L., Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, Feenstra, Bjarke, Pers, Tune Hannes, Bønnelykke, Klaus, van der Valk, Ralf J.P., Kreiner-Møller, Eskil, Kooijman, Marjolein N., Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P., Geller, Frank, Hayes, M. Geoffrey, Cousminer, Diana L., Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, Feenstra, Bjarke, Pers, Tune Hannes, and Bønnelykke, Klaus

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P <1 × 10−6) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10−8, explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10−4) and adult height (N = 127 513; P = 1.45 × 10−5). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Published
2015

11. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R, Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M T, Murray, Clare S, Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I, Buxton, Jessica L, Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S, Ang, Wei, Newnham, John P, Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T, Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I, Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N, Pers, Tune H, Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W, Melén, Erik, Grant, Struan F A, Feenstra, Bjarke, Lowe, William L, Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H, Pennell, Craig E, Niinikoski, Harri, Dedoussis, George V, Mccarthy, Mark I, Frayling, Timothy M, Sunyer, Jordi, Timpson, Nicholas J, Rivadeneira, Fernando, Bønnelykke, Klaus, Jaddoe, Vincent W V, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R, Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M T, Murray, Clare S, Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I, Buxton, Jessica L, Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S, Ang, Wei, Newnham, John P, Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T, Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I, Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N, Pers, Tune H, Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W, Melén, Erik, Grant, Struan F A, Feenstra, Bjarke, Lowe, William L, Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H, Pennell, Craig E, Niinikoski, Harri, Dedoussis, George V, Mccarthy, Mark I, Frayling, Timothy M, Sunyer, Jordi, Timpson, Nicholas J, Rivadeneira, Fernando, Bønnelykke, Klaus, and Jaddoe, Vincent W V

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Published
2015
Full Text
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12. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R, Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M T, Murray, Clare S, Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I, Buxton, Jessica L, Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S, Ang, Wei, Newnham, John P, Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T, Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I, Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N, Pers, Tune H, Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W, Melén, Erik, Grant, Struan F A, Feenstra, Bjarke, Lowe, William L, Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H, Pennell, Craig E, Niinikoski, Harri, Dedoussis, George V, Mccarthy, Mark I, Frayling, Timothy M, Sunyer, Jordi, Timpson, Nicholas J, Rivadeneira, Fernando, Bønnelykke, Klaus, Jaddoe, Vincent W V, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R, Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M T, Murray, Clare S, Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I, Buxton, Jessica L, Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S, Ang, Wei, Newnham, John P, Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T, Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I, Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N, Pers, Tune H, Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W, Melén, Erik, Grant, Struan F A, Feenstra, Bjarke, Lowe, William L, Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H, Pennell, Craig E, Niinikoski, Harri, Dedoussis, George V, Mccarthy, Mark I, Frayling, Timothy M, Sunyer, Jordi, Timpson, Nicholas J, Rivadeneira, Fernando, Bønnelykke, Klaus, and Jaddoe, Vincent W V

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Published
2015
Full Text
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13. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R, Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M T, Murray, Clare S, Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I, Buxton, Jessica L, Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S, Ang, Wei, Newnham, John P, Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T, Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I, Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N, Pers, Tune H, Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W, Melén, Erik, Grant, Struan F A, Feenstra, Bjarke, Lowe, William L, Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H, Pennell, Craig E, Niinikoski, Harri, Dedoussis, George V, Mccarthy, Mark I, Frayling, Timothy M, Sunyer, Jordi, Timpson, Nicholas J, Rivadeneira, Fernando, Bønnelykke, Klaus, Jaddoe, Vincent W V, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R, Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M T, Murray, Clare S, Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I, Buxton, Jessica L, Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S, Ang, Wei, Newnham, John P, Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T, Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I, Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N, Pers, Tune H, Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W, Melén, Erik, Grant, Struan F A, Feenstra, Bjarke, Lowe, William L, Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H, Pennell, Craig E, Niinikoski, Harri, Dedoussis, George V, Mccarthy, Mark I, Frayling, Timothy M, Sunyer, Jordi, Timpson, Nicholas J, Rivadeneira, Fernando, Bønnelykke, Klaus, and Jaddoe, Vincent W V

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Published
2015
Full Text
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14. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R, Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M T, Murray, Clare S, Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I, Buxton, Jessica L, Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S, Ang, Wei, Newnham, John P, Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T, Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I, Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N, Pers, Tune H, Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W, Melén, Erik, Grant, Struan F A, Feenstra, Bjarke, Lowe, William L, Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H, Pennell, Craig E, Niinikoski, Harri, Dedoussis, George V, Mccarthy, Mark I, Frayling, Timothy M, Sunyer, Jordi, Timpson, Nicholas J, Rivadeneira, Fernando, Bønnelykke, Klaus, Jaddoe, Vincent W V, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Palotie, Aarno, Bustamante, Mariona, Estivill, Xavier, Gonzalez, Juan R, Llop, Sabrina, Kiess, Wieland, Mahajan, Anubha, Flexeder, Claudia, Tiesler, Carla M T, Murray, Clare S, Simpson, Angela, Magnus, Per, Sengpiel, Verena, Hartikainen, Anna-Liisa, Keinanen-Kiukaanniemi, Sirkka, Lewin, Alexandra, Da Silva Couto Alves, Alexessander, Blakemore, Alexandra I, Buxton, Jessica L, Kaakinen, Marika, Rodriguez, Alina, Sebert, Sylvain, Vaarasmaki, Marja, Lakka, Timo, Lindi, Virpi, Gehring, Ulrike, Postma, Dirkje S, Ang, Wei, Newnham, John P, Lyytikäinen, Leo-Pekka, Pahkala, Katja, Raitakari, Olli T, Panoutsopoulou, Kalliope, Zeggini, Eleftheria, Boomsma, Dorret I, Groen-Blokhuis, Maria, Ilonen, Jorma, Franke, Lude, Hirschhorn, Joel N, Pers, Tune H, Liang, Liming, Huang, Jinyan, Hocher, Berthold, Knip, Mikael, Saw, Seang-Mei, Holloway, John W, Melén, Erik, Grant, Struan F A, Feenstra, Bjarke, Lowe, William L, Widén, Elisabeth, Sergeyev, Elena, Grallert, Harald, Custovic, Adnan, Jacobsson, Bo, Jarvelin, Marjo-Riitta, Atalay, Mustafa, Koppelman, Gerard H, Pennell, Craig E, Niinikoski, Harri, Dedoussis, George V, Mccarthy, Mark I, Frayling, Timothy M, Sunyer, Jordi, Timpson, Nicholas J, Rivadeneira, Fernando, Bønnelykke, Klaus, and Jaddoe, Vincent W V

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Published
2015
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15. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

LS IRAS EEPI ME (Milieu epidemiologie), IRAS RATIA2, Risk Assessment, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Gehring, Ulrike, Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, LS IRAS EEPI ME (Milieu epidemiologie), IRAS RATIA2, Risk Assessment, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Gehring, Ulrike, and Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium

Published
2015

16. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

LS IRAS EEPI ME (Milieu epidemiologie), IRAS RATIA2, Risk Assessment, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Gehring, Ulrike, Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, LS IRAS EEPI ME (Milieu epidemiologie), IRAS RATIA2, Risk Assessment, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Gehring, Ulrike, and Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium

Published
2015

17. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author

LS IRAS EEPI ME (Milieu epidemiologie), IRAS RATIA2, Risk Assessment, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Gehring, Ulrike, Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, LS IRAS EEPI ME (Milieu epidemiologie), IRAS RATIA2, Risk Assessment, van der Valk, Ralf J P, Kreiner-Møller, Eskil, Kooijman, Marjolein N, Guxens, Mònica, Stergiakouli, Evangelia, Sääf, Annika, Bradfield, Jonathan P, Geller, Frank, Hayes, M Geoffrey, Cousminer, Diana L, Körner, Antje, Thiering, Elisabeth, Curtin, John A, Myhre, Ronny, Huikari, Ville, Joro, Raimo, Kerkhof, Marjan, Warrington, Nicole M, Pitkänen, Niina, Ntalla, Ioanna, Horikoshi, Momoko, Veijola, Riitta, Freathy, Rachel M, Teo, Yik-Ying, Barton, Sheila J, Evans, David M, Kemp, John P, St Pourcain, Beate, Ring, Susan M, Davey Smith, George, Bergström, Anna, Kull, Inger, Hakonarson, Hakon, Mentch, Frank D, Bisgaard, Hans, Chawes, Bo, Stokholm, Jakob, Waage, Johannes, Eriksen, Patrick, Sevelsted, Astrid, Melbye, Mads, van Duijn, Cornelia M, Medina-Gomez, Carolina, Hofman, Albert, de Jongste, Johan C, Taal, H Rob, Uitterlinden, André G, Armstrong, Loren L, Eriksson, Johan, Gehring, Ulrike, and Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium

Published
2015

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