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Warrington, Nicole ; Beaumont, Robin ; 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 ; Chen, Jia ; Nodzenski, Michael ; Schnurr, Theresia M. ; Zafarmand, Mohammad Hadi ; Bradfield, Jonathan P. ; Grarup, Niels ; Kooijman, Marjolein N. ; Li-Gao, Ruifang ; Geller, Frank ; Ahluwalia, Tarunveer Singh ; Paternoster, Lavinia ; Rueedi, Rico ; Huikari, Ville ; Hottenga, Jouke-Jan ; Lyytikäinen, Leo-Pekka ; Cavadino, Alana ; Metrustry, Sarah ; Cousminer, Diana L. ; Wu, Ying ; Thiering, Elisabeth Paula ; Wang, Carol A. ; Have, Christian Theil ; 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 ; Morgen, Camilla S. ; van Kampen, Antoine H. C. ; van Schaik, Barbera D. C. ; Mentch, Frank D. ; Langenberg, Claudia ; 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 Esmann ; Trier, Caecilie ; van Beijsterveldt, Catharina E. M. ; Murcia, Mario ; Bustamante, Mariona ; Bonàs-Guarch, Sílvia ; Hougaard, David M. ; Mercader, Josep M. ; Linneberg, Allan ; Schraut, Katharina E. ; Lind, Penelope A. ; Medland, Sarah Elizabeth ; 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 Fleischer ; Eloranta, Aino-Maija ; Lakka, Timo A. ; van Duijn, Cornelia M. ; Kiess, Wieland ; Koerner, 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. ; Widen, Elisabeth E. ; Hattersley, Andrew T. ; Spector, Tim D. ; Kaehoenen, Mika ; Viikari, Jorma S. ; Lehtimaeki, Terho ; Boomsma, Dorret I. ; Sebert, Sylvain ; Vollenweider, Peter ; Sorensen, Thorkild I. A. ; Bisgaard, Hans ; Bonnelykke, 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, Andre G. ; Jarvelin, Marjo-Riitta ; Power, Christine ; Hypponen, Elina ; Scholtens, Denise M. ; Lowe, William L. ; Smith, George Davey ; Timpson, Nicholas J. ; Morris, Andrew P. ; Wareham, Nicholas J. ; Hakonarson, Hakon ; Grant, Struan F. A. ; Frayling, Timothy M. ; Lawlor, Debbie A. ; Njolstad, Pal R. ; Johansson, Stefan ; Ong, Ken K. ; McCarthy, Mark I. ; Perry, John R. B. ; Evans, David M. ; Freathy, Rachel M.
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.
Taal, H. Rob ; St Pourcain, Beate ; Thiering, Elisabeth ; Das, Shikta ; Mook-Kanamori, Dennis O. ; Warrington, Nicole M. ; Kaakinen, Marika ; Kreiner-Moller, Eskil ; Bradfield, Jonathan P. ; Freathy, Rachel M. ; Geller, Frank ; Guxens, Monica ; Cousminer, Diana L. ; Kerkhof, Marjan ; Timpson, Nicholas J. ; Ikram, M. Arfan ; Beilin, Lawrence J. ; Bonnelykke, Klaus ; Buxton, Jessica L. ; Charoen, Pimphen ; Chawes, Bo Lund Krogsgaard ; Eriksson, Johan ; Evans, David M. ; Hofman, Albert ; Kemp, John P. ; Kim, Cecilia E. ; Klopp, Norman ; Lahti, Jari ; Lye, Stephen J. ; McMahon, George ; Mentch, Frank D. ; Mueller-Nurasyid, Martina ; O'Reilly, Paul F. ; Prokopenko, Inga ; Rivadeneira, Fernando ; Steegers, Eric A. P. ; Sunyer, Jordi ; Tiesler, Carla ; Yaghootkar, Hanieh ; Breteler, Monique M. B. ; Debette, Stephanie ; Fornage, Myriam ; Gudnason, Vilmundur ; Launer, Lenore J. ; van der Lugt, Aad ; Mosley, Thomas H. ; Seshadri, Sudha ; Smith, Albert V. ; Vernooij, Meike W. ; Blakemore, Alexandra I. F. ; Chiavacci, Rosetta M. ; Feenstra, Bjarke ; Fernandez-Banet, Julio ; Grant, Struan F. A. ; Hartikainen, Anna-Liisa ; van der Heijden, Albert J. ; Iniguez, Carmen ; Lathrop, Mark ; McArdle, Wendy L. ; Molgaard, Anne ; Newnham, John P. ; Palmer, Lyle J. ; Palotie, Aarno ; Pouta, Annneli ; Ring, Susan M. ; Sovio, Ulla ; Standl, Marie ; Uitterlinden, Andre G. ; Wichmann, H-Erich ; Vissing, Nadja Hawwa ; DeCarli, Charles ; van Duijn, Cornelia M. ; McCarthy, Mark I. ; Koppelman, Gerard H. ; Estivill, Xavier ; Hattersley, Andrew T. ; Melbye, Mads ; Bisgaard, Hans ; Pennell, Craig E. ; Widen, Elisabeth ; Hakonarson, Hakon ; Smith, George Davey ; Heinrich, Joachim ; Jarvelin, Marjo-Riitta ; Jaddoe, Vincent W. V. ; Adair, Linda S. ; Ang, Wei ; Atalay, Mustafa ; van Beijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Bradfield, Jonathan P. ; Charoen, Pimphen ; Coin, Lachlan ; Cousminer, Diana L. ; Das, Shikta ; Davis, Oliver S. P. ; Elliott, Paul ; Evans, David M. ; Feenstra, Bjarke ; Flexeder, Claudia ; Frayling, Tim ; Freathy, Rachel M. ; Gaillard, Romy ; Geller, Frank ; Groen-Blokhuis, Maria ; Goh, Liang-Kee ; Guxens, Monica ; Haworth, Claire M. A. ; Hadley, Dexter ; Hebebrand, Johannes ; Hinney, Anke ; Hirschhorn, Joel N. ; Holloway, John W. ; Holst, Claus ; Hottenga, Jouke Jan ; Horikoshi, Momoko ; Huikari, Ville ; Hypponen, Elina ; Iniguez, Carmen ; Kaakinen, Marika ; Kilpelainen, Tuomas O. ; Kirin, Mirna ; Kowgier, Matthew ; Lakka, Hanna-Maaria ; Lange, Leslie A. ; Lawlor, Debbie A. ; Lehtimaki, Terho ; Lewin, Alex ; Lindgren, Cecilia ; Lindi, Virpi ; Maggi, Reedik ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Mook-Kanamori, Dennis O. ; Murray, Jeffrey C. ; Nivard, Michel ; Nohr, Ellen Aagaard ; Ntalla, Ioanna ; Oken, Emily ; O'Reilly, Paul F. ; Palmer, Lyle J. ; Panoutsopoulou, Kalliope ; Pararajasingham, Jennifer ; Prokopenko, Inga ; Rodriguez, Alina ; Salem, Rany M. ; Sebert, Sylvain ; Siitonen, Niina ; Sovio, Ulla ; St Pourcain, Beate ; Strachan, David P. ; Sunyer, Jordi ; Taal, H. Rob ; Teo, Yik-Ying ; Thiering, Elisabeth ; Tiesler, Carla ; Uitterlinden, Andre G. ; Valcarcel, Beatriz ; Warrington, Nicole M. ; White, Scott ; Willemsen, Gonneke ; Yaghootkar, Hanieh ; Zeggini, Eleftheria ; Boomsma, Dorret I. ; Cooper, Cyrus ; Estivill, Xavier ; Gillman, Matthew ; Grant, Struan F. A. ; Hakonarson, Hakon ; Hattersley, Andrew T. ; Heinrich, Joachim ; Hocher, Berthold ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; Lakka, Timo A. ; McCarthy, Mark I. ; Melbye, Mads ; Mohlke, Karen L. ; Dedoussis, George V. ; Ong, Ken K. ; Pearson, Ewan R. ; Pennell, Craig E. ; Price, Thomas S. ; Power, Chris ; Raitakari, Olli T. ; Saw, Seang-Mei ; Scherag, Andre ; Simell, Olli ; Sorensen, Thorkild I. A. ; Timpson, Nicholas J. ; Widen, Elisabeth ; Wilson, James F. ; Ang, Wei ; van Beijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Bradfield, Jonathan P. ; Charoen, Pimphen ; Coin, Lachlan ; Cousminer, Diana L. ; Das, Shikta ; Elliott, Paul ; Evans, David M. ; Frayling, Tim ; Freathy, Rachel M. ; Gaillard, Romy ; Groen-Blokhuis, Maria ; Guxens, Monica ; Hadley, Dexter ; Hottenga, Jouke Jan ; Huikari, Ville ; Hypponen, Elina ; Kaakinen, Marika ; Kowgier, Matthew ; Lawlor, Debbie A. ; Lewin, Alex ; Lindgren, Cecilia ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Mook-Kanamori, Dennis O. ; Nivard, Michel ; O'Reilly, Paul F. ; Palmer, Lyle J. ; Prokopenko, Inga ; Rodriguez, Alina ; Sebert, Sylvain ; Sovio, Ulla ; St Pourcain, Beate ; Standl, Marie ; Strachan, David P. ; Sunyer, Jordi ; Taal, H. Rob ; Thiering, Elisabeth ; Tiesler, Carla ; Uitterlinden, Andre G. ; Valcarcel, Beatriz ; Warrington, Nicole M. ; White, Scott ; Willemsen, Gonneke ; Yaghootkar, Hanieh ; Boomsma, Dorret I. ; Estivill, Xavier ; Grant, Struan F. A. ; Hakonarson, Hakon ; Hattersley, Andrew T. ; Heinrich, Joachim ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; McCarthy, Mark I. ; Pennell, Craig E. ; Power, Chris ; Timpson, Nicholas J. ; Widen, Elisabeth ; Ikram, M. Arfan ; Fornage, Myriam ; Smith, Albert V. ; Seshadri, Sudha ; Schmidt, Reinhold ; Debette, Stephanie ; Vrooman, Henri A. ; Sigurdsson, Sigurdur ; Ropele, Stefan ; Coker, Laura H. ; Longstreth, W. T. ; Niessen, Wiro J. ; DeStefano, Anita L. ; Beiser, Alexa ; Zijdenbos, Alex P. ; Struchalin, Maksim ; Jack, Clifford R. ; Nalls, Mike A. ; Au, Rhoda ; Hofman, Albert ; Gudnason, Haukur ; van der Lugt, Aad ; Harris, Tamara B. ; Meeks, William M. ; Vernooij, Meike W. ; van Buchem, Mark A. ; Catellier, Diane ; Gudnason, Vilmundur ; Windham, B. Gwen ; Wolf, Philip A. ; van Duijn, Cornelia M. ; Mosley, Thomas H. ; Schmidt, Helena ; Launer, Lenore J. ; Breteler, Monique M. B. ; DeCarli, Charles
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
Middeldorp, Christel M. ; Mahajan, Anubha ; Horikoshi, Momoko ; Robertson, Neil R. ; Beaumont, Robin N. ; Bradfield, Jonathan P. ; Bustamante, Mariona ; Cousminer, Diana L. ; Day, Felix R. ; De Silva, N. Maneka ; Guxens, Monica ; Mook-Kanamori, Dennis O. ; St Pourcain, Beate ; Warrington, Nicole M. ; Adair, Linda S. ; Ahlqvist, Emma ; Ahluwalia, Tarunveer Singh ; Almgren, Peter ; Ang, Wei ; Atalay, Mustafa ; Auvinen, Juha ; Bartels, Meike ; Beckmann, Jacques S. ; Bilbao, Jose Ramon ; Bond, Tom ; Borja, Judith B. ; Cavadino, Alana ; Charoen, Pimphen ; Chen, Zhanghua ; Coin, Lachlan ; Cooper, Cyrus ; Curtin, John A. ; Custovic, Adnan ; Das, Shikta ; Davies, Gareth E. ; Dedoussis, George V. ; Duijts, Liesbeth ; Eastwood, Peter R. ; Eliasen, Anders U. ; Elliott, Paul ; Eriksson, Johan G. ; Estivill, Xavier ; Fadista, Joao ; Fedko, Iryna O. ; Frayling, Timothy M. ; Gaillard, Romy ; Gauderman, W. James ; Geller, Frank ; Gilliland, Frank ; Gilsanz, Vincente ; Granell, Raquel ; Grarup, Niels ; Groop, Leif ; Hadley, Dexter ; Hakonarson, Hakon ; Hansen, Torben ; Hartman, Catharina A. ; Hattersley, Andrew T. ; Hayes, M. Geoffrey ; Hebebrand, Johannes ; Heinrich, Joachim ; Helgeland, Oyvind ; Henders, Anjali K. ; Henderson, John ; Henriksen, Tine B. ; Hirschhorn, Joel N. ; Hivert, Marie-France ; Hocher, Berthold ; Holloway, John W. ; Holt, Patrick ; Hottenga, Jouke-Jan ; Hypponen, Elina ; Iniguez, Carmen ; Johansson, Stefan ; Jugessur, Astanand ; Kahonen, Mika ; Kalkwarf, Heidi J. ; Kaprio, Jaakko ; Karhunen, Ville ; Kemp, John P. ; Kerkhof, Marjan ; Koppelman, Gerard H. ; Korner, Antje ; Kotecha, Sailesh ; Kreiner-Moller, Eskil ; Kulohoma, Benard ; Kumar, Ashish ; Kutalik, Zoltan ; Lahti, Jari ; Lappe, Joan M. ; Larsson, Henrik ; Lehtimaki, Terho ; Lewin, Alexandra M. ; Li, Jin ; Lichtenstein, Paul ; Lindgren, Cecilia M. ; Lindi, Virpi ; Linneberg, Allan ; Liu, Xueping ; Liu, Jun ; Lowe, William L. ; Lundstrom, Sebastian ; Lyytikainen, Leo-Pekka ; Ma, Ronald C. W. ; Mace, Aurelien ; Magi, Reedik ; Magnus, Per ; Mamun, Abdullah A. ; Mannikko, Minna ; Martin, Nicholas G. ; Mbarek, Hamdi ; McCarthy, Nina S. ; Medland, Sarah E. ; Melbye, Mads ; Melen, Erik ; Mohlke, Karen L. ; Monnereau, Claire ; Morgen, Camilla S. ; Morris, Andrew P. ; Murray, Jeffrey C. ; Myhre, Ronny ; Najman, Jackob M. ; Nivard, Michel G. ; Nohr, Ellen A. ; Nolte, Ilja M. ; Ntalla, Ioanna ; Oberfield, Sharon E. ; Oken, Emily ; Oldehinkel, Albertine J. ; Pahkala, Katja ; Palviainen, Teemu ; Panoutsopoulou, Kalliope ; Pedersen, Oluf ; Pennell, Craig E. ; Pershagen, Goran ; Pitkanen, Niina ; Plomin, Robert ; Power, Christine ; Prasad, Rashmi B. ; Prokopenko, Inga ; Pulkkinen, Lea ; Raikkonen, Katri ; Raitakari, Olli T. ; Reynolds, Rebecca M. ; Richmond, Rebecca C. ; Rivadeneira, Fernando ; Rodriguez, Alina ; Rose, Richard J. ; Salem, Rany ; Santa-Marina, Loreto ; Saw, Seang-Mei ; Schnurr, Theresia M. ; Scott, James G. ; Selzam, Saskia ; Shepherd, John A. ; Simpson, Angela ; Skotte, Line ; Sleiman, Patrick M. A. ; Snieder, Harold ; Sorensen, Thorkild I. A. ; Standl, Marie ; Steegers, Eric A. P. ; Strachan, David P. ; Straker, Leon ; Strandberg, Timo ; Taylor, Michelle ; Teo, Yik-Ying ; Thiering, Elisabeth ; Torrent, Maties ; Tyrrell, Jessica ; Uitterlinden, Andre G. ; van Beijsterveldt, Toos ; van der Most, Peter J. ; van Duijn, Cornelia M. ; Viikari, Jorma ; Vilor-Tejedor, Natalia ; Vogelezang, Suzanne ; Vonk, Judith M. ; Vrijkotte, Tanja G. M. ; Vuoksimaa, Eero ; Wang, Carol A. ; Watkins, William J. ; Wichmann, H-Erich ; Willemsen, Gonneke ; Williams, Gail M. ; Wilson, James F. ; Wray, Naomi R. ; Xu, Shujing ; Xu, Cheng-Jian ; Yaghootkar, Hanieh ; Yi, Lu ; Zafarmand, Mohammad Hadi ; Zeggini, Eleftheria ; Zemel, Babette S. ; Hinney, Anke ; Lakka, Timo A. ; Whitehouse, Andrew J. O. ; Sunyer, Jordi ; Widen, Elisabeth E. ; Feenstra, Bjarke ; Sebert, Sylvain ; Jacobsson, Bo ; Njolstad, Pal R. ; Stoltenberg, Camilla ; Smith, George Davey ; Lawlor, Debbie A. ; Paternoster, Lavinia ; Timpson, Nicholas J. ; Ong, Ken K. ; Bisgaard, Hans ; Bonnelykke, Klaus ; Jaddoe, Vincent W. V. ; Tiemeier, Henning ; Jarvelin, Marjo-Riitta ; Evans, David M. ; Perry, John R. B. ; Grant, Struan F. A. ; Boomsma, Dorret I. ; Freathy, Rachel M. ; McCarthy, Mark I. ; Felix, Janine F.
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Ikram, M. Arfan ; Fornage, Myriam ; Smith, Albert V. ; Seshadri, Sudha ; Schmidt, Reinhold ; Debette, Stephanie ; Vrooman, Henri A. ; Sigurdsson, Sigurdur ; Ropele, Stefan ; Taal, H. Rob ; Mook-Kanamori, Dennis O. ; Coker, Laura H. ; Longstreth, W. T. ; Niessen, Wiro J. ; DeStefano, Anita L. ; Beiser, Alexa ; Zijdenbos, Alex P. ; Struchalin, Maksim ; Jack, Clifford R. ; Rivadeneira, Fernando ; Uitterlinden, Andre G. ; Knopman, David S. ; Hartikainen, Anna-Liisa ; Pennell, Craig E. ; Thiering, Elisabeth ; Steegers, Eric A. P. ; Hakonarson, Hakon ; Heinrich, Joachim ; Palmer, Lyle J. ; Jarvelin, Marjo-Riitta ; McCarthy, Mark I. ; Grant, Struan F. A. ; St Pourcain, Beate ; Timpson, Nicholas J. ; Smith, George Davey ; Sovio, Ulla ; Nalls, Mike A. ; Au, Rhoda ; Hofman, Albert ; Gudnason, Haukur ; van der Lugt, Aad ; Harris, Tamara B. ; Meeks, William M. ; Vernooij, Meike W. ; van Buchem, Mark A. ; Catellier, Diane ; Jaddoe, Vincent W. V. ; Gudnason, Vilmundur ; Windham, B. Gwen ; Wolf, Philip A. ; van Duijn, Cornelia M. ; Mosley, Thomas H. ; Schmidt, Helena ; Launer, Lenore J. ; Breteler, Monique M. B. ; DeCarli, Charles ; Adair, Linda S. ; Ang, Wei ; Atalay, Mustafa ; vanBeijsterveldt, Toos ; Bergen, Nienke ; Benke, Kelly ; Berry, Diane J. ; Coin, Lachlan ; Davis, Oliver S. P. ; Elliott, Paul ; Flexeder, Claudia ; Frayling, Tim ; Gaillard, Romy ; Groen-Blokhuis, Maria ; Goh, Liang-Kee ; Haworth, Claire M. A. ; Hadley, Dexter ; Hebebrand, Johannes ; Hinney, Anke ; Hirschhorn, Joel N. ; Holloway, John W. ; Holst, Claus ; Hottenga, Jouke Jan ; Horikoshi, Momoko ; Huikari, Ville ; Hypponen, Elina ; Kilpelainen, Tuomas O. ; Kirin, Mirna ; Kowgier, Matthew ; Lakka, Hanna-Maaria ; Lange, Leslie A. ; Lawlor, Debbie A. ; Lehtimaki, Terho ; Lewin, Alex ; Lindgren, Cecilia ; Lindi, Virpi ; Maggi, Reedik ; Marsh, Julie ; Middeldorp, Christel ; Millwood, Iona ; Murray, Jeffrey C. ; Nivard, Michel ; Nohr, Ellen Aagaard ; Ntalla, Ioanna ; Oken, Emily ; Panoutsopoulou, Kalliope ; Pararajasingham, Jennifer ; Rodriguez, Alina ; Salem, Rany M. ; Sebert, Sylvain ; Siitonen, Niina ; Strachan, David P. ; Teo, Yik-Ying ; Valcarcel, Beatriz ; Willemsen, Gonneke ; Zeggini, Eleftheria ; Boomsma, Dorret I. ; Cooper, Cyrus ; Gillman, Matthew ; Hocher, Berthold ; Lakka, Timo A. ; Mohlke, Karen L. ; Dedoussis, George V. ; Ong, Ken K. ; Pearson, Ewan R. ; Price, Thomas S. ; Power, Chris ; Raitakari, Olli T. ; Saw, Seang-Mei ; Scherag, Andre ; Simell, Olli ; Sorensen, Thorkild I. A. ; Wilson, James F.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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