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Horikoshi, Momoko ; Yaghootkar, Hanieh ; Mook-Kanamori, Dennis O. ; Sovio, Ulla ; Taal, H. Rob ; Hennig, Branwen J. ; Bradfield, Jonathan P. ; St Pourcain, Beate ; Evans, David M. ; Charoen, Pimphen ; Kaakinen, Marika ; Cousminer, Diana L. ; Lehtimaki, Terho ; Kreiner-Moller, Eskil ; Warrington, Nicole M. ; Bustamante, Mariona ; Feenstra, Bjarke ; Berry, Diane J. ; Thiering, Elisabeth ; Pfab, Thiemo ; Barton, Sheila J. ; Shields, Beverley M. ; Kerkhof, Marjan ; van Leeuwen, Elisabeth M. ; Fulford, Anthony J. ; Kutalik, Zoltan ; Zhao, Jing Hua ; den Hoed, Marcel ; Mahajan, Anubha ; Lindi, Virpi ; Goh, Liang-Kee ; Hottenga, Jouke-Jan ; Wu, Ying ; Raitakari, Olli T. ; Harder, Marie N. ; Meirhaeghe, Aline ; Ntalla, Ioanna ; Salem, Rany M. ; Jameson, Karen A. ; Zhou, Kaixin ; Monies, Dorota M. ; Lagou, Vasiliki ; Kirin, Mirna ; Heikkinen, Jani ; Adair, Linda S. ; Alkuraya, Fowzan S. ; Al-Odaib, Ali ; Amouyel, Philippe ; Andersson, Ehm Astrid ; Bennett, Amanda J. ; Blakemore, Alexandra I. F. ; Buxton, Jessica L. ; Dallongeville, Jean ; Das, Shikta ; de Geus, Eco J. C. ; Estivill, Xavier ; Flexeder, Claudia ; Froguel, Philippe ; Geller, Frank ; Godfrey, Keith M. ; Gottrand, Frederic ; Groves, Christopher J. ; Hansen, Torben ; Hirschhorn, Joel N. ; Hofman, Albert ; Hollegaard, Mads V. ; Hougaard, David M. ; Hyppoenen, Elina ; Inskip, Hazel M. ; Isaacs, Aaron ; Jorgensen, Torben ; Kanaka-Gantenbein, Christina ; Kemp, John P. ; Kiess, Wieland ; Kilpelainen, Tuomas O. ; Klopp, Norman ; Knight, Bridget A. ; Kuzawa, Christopher W. ; McMahon, George ; Newnham, John P. ; Niinikoski, Harri ; Oostra, Ben A. ; Pedersen, Louise ; Postma, Dirkje S. ; Ring, Susan M. ; Rivadeneira, Fernando ; Robertson, Neil R. ; Sebert, Sylvain ; Simell, Olli ; Slowinski, Torsten ; Tiesler, Carla M. T. ; Toenjes, Anke ; Vaag, Allan ; Viikari, Jorma S. ; Vink, Jacqueline M. ; Vissing, Nadja Hawwa ; Wareham, Nicholas J. ; Willemsen, Gonneke ; Witte, Daniel R. ; Zhang, Haitao ; Zhao, Jianhua ; Wilson, James F. ; Stumvoll, Michael ; Prentice, Andrew M. ; Meyer, Brian F. ; Pearson, Ewan R. ; Boreham, Colin A. G. ; Cooper, Cyrus ; Gillman, Matthew W. ; Dedoussis, George V. ; Moreno, Luis A. ; Pedersen, Oluf ; Saarinen, Maiju ; Mohlke, Karen L. ; Boomsma, Dorret I. ; Saw, Seang-Mei ; Lakka, Timo A. ; Koerner, Antje ; Loos, Ruth J. F. ; Ong, Ken K. ; Vollenweider, Peter ; van Duijn, Cornelia M. ; Koppelman, Gerard H. ; Hattersley, Andrew T. ; Holloway, John W. ; Hocher, Berthold ; Heinrich, Joachim ; Power, Chris ; Melbye, Mads ; Guxens, Monica ; Pennell, Craig E. ; Bonnelykke, Klaus ; Bisgaard, Hans ; Eriksson, Johan G. ; Widen, Elisabeth ; Hakonarson, Hakon ; Uitterlinden, Andre G. ; Pouta, Anneli ; Lawlor, Debbie A. ; Smith, George Davey ; Frayling, Timothy M. ; McCarthy, Mark I. ; Grant, Struan F. A. ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; Timpson, Nicholas J. ; Prokopenko, Inga ; Freathy, Rachel M.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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.
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