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Common variants at 12q15 and 12q24 are associated with infant head circumference

H. Rob Taal, Beate St Pourcain, Elisabeth Thiering, Shikta Das, Dennis O. Mook-Kanamori, Nicole M. Warrington, Marika Kaakinen, Eskil Kreiner-Moller, Jonathan P. Bradfield, Rachel M. Freathy, Frank Geller, Monica Guxens, Diana L. Cousminer, Marjan Kerkhof, Nicholas J. Timpson, M. Arfan Ikram, Lawrence J. Beilin, Klaus Bonnelykke, Jessica L. Buxton, Pimphen Charoen, Bo Lund Krogsgaard Chawes, Johan Eriksson, David M. Evans, Albert Hofman, John P. Kemp, Cecilia E. Kim, Norman Klopp, Jari Lahti, Stephen J. Lye, George McMahon, Frank D. Mentch, Martina Mueller-Nurasyid, Paul F. O'Reilly, Inga Prokopenko, Fernando Rivadeneira, Eric A. P. Steegers, Jordi Sunyer, Carla Tiesler, Hanieh Yaghootkar, Monique M. B. Breteler, Stephanie Debette, Myriam Fornage, Vilmundur Gudnason, Lenore J. Launer, Aad van der Lugt, Thomas H. Mosley, Sudha Seshadri, Albert V. Smith, Meike W. Vernooij, Alexandra I. F. Blakemore, Rosetta M. Chiavacci, Bjarke Feenstra, Julio Fernandez-Banet, Struan F. A. Grant, Anna-Liisa Hartikainen, Albert J. van der Heijden, Carmen Iniguez, Mark Lathrop, Wendy L. McArdle, Anne Molgaard, John P. Newnham, Lyle J. Palmer, Aarno Palotie, Annneli Pouta, Susan M. Ring, Ulla Sovio, Marie Standl, Andre G. Uitterlinden, H-Erich Wichmann, Nadja Hawwa Vissing, Charles DeCarli, Cornelia M. van Duijn, Mark I. McCarthy, Gerard H. Koppelman, Xavier Estivill, Andrew T. Hattersley, Mads Melbye, Hans Bisgaard, Craig E. Pennell, Elisabeth Widen, Hakon Hakonarson, George Davey Smith, Joachim Heinrich, Marjo-Riitta Jarvelin, Vincent W. V. Jaddoe, Linda S. Adair, Wei Ang, Mustafa Atalay, Toos van Beijsterveldt, Nienke Bergen, Kelly Benke, Diane J. Berry, Jonathan P. Bradfield, Pimphen Charoen, Lachlan Coin, Diana L. Cousminer, Shikta Das, Oliver S. P. Davis, Paul Elliott, David M. Evans, Bjarke Feenstra, Claudia Flexeder, Tim Frayling, Rachel M. Freathy, Romy Gaillard, Frank Geller, Maria Groen-Blokhuis, Liang-Kee Goh, Monica Guxens, Claire M. A. Haworth, Dexter Hadley, Johannes Hebebrand, Anke Hinney, Joel N. Hirschhorn, John W. Holloway, Claus Holst, Jouke Jan Hottenga, Momoko Horikoshi, Ville Huikari, Elina Hypponen, Carmen Iniguez, Marika Kaakinen, Tuomas O. Kilpelainen, Mirna Kirin, Matthew Kowgier, Hanna-Maaria Lakka, Leslie A. Lange, Debbie A. Lawlor, Terho Lehtimaki, Alex Lewin, Cecilia Lindgren, Virpi Lindi, Reedik Maggi, Julie Marsh, Christel Middeldorp, Iona Millwood, Dennis O. Mook-Kanamori, Jeffrey C. Murray, Michel Nivard, Ellen Aagaard Nohr, Ioanna Ntalla, Emily Oken, Paul F. O'Reilly, Lyle J. Palmer, Kalliope Panoutsopoulou, Jennifer Pararajasingham, Inga Prokopenko, Alina Rodriguez, Rany M. Salem, Sylvain Sebert, Niina Siitonen, Ulla Sovio, Beate St Pourcain, David P. Strachan, Jordi Sunyer, H. Rob Taal, Yik-Ying Teo, Elisabeth Thiering, Carla Tiesler, Andre G. Uitterlinden, Beatriz Valcarcel, Nicole M. Warrington, Scott White, Gonneke Willemsen, Hanieh Yaghootkar, Eleftheria Zeggini, Dorret I. Boomsma, Cyrus Cooper, Xavier Estivill, Matthew Gillman, Struan F. A. Grant, Hakon Hakonarson, Andrew T. Hattersley, Joachim Heinrich, Berthold Hocher, Vincent W. V. Jaddoe, Marjo-Riitta Jarvelin, Timo A. Lakka, Mark I. McCarthy, Mads Melbye, Karen L. Mohlke, George V. Dedoussis, Ken K. Ong, Ewan R. Pearson, Craig E. Pennell, Thomas S. Price, Chris Power, Olli T. Raitakari, Seang-Mei Saw, Andre Scherag, Olli Simell, Thorkild I. A. Sorensen, Nicholas J. Timpson, Elisabeth Widen, James F. Wilson, Wei Ang, Toos van Beijsterveldt, Nienke Bergen, Kelly Benke, Diane J. Berry, Jonathan P. Bradfield, Pimphen Charoen, Lachlan Coin, Diana L. Cousminer, Shikta Das, Paul Elliott, David M. Evans, Tim Frayling, Rachel M. Freathy, Romy Gaillard, Maria Groen-Blokhuis, Monica Guxens, Dexter Hadley, Jouke Jan Hottenga, Ville Huikari, Elina Hypponen, Marika Kaakinen, Matthew Kowgier, Debbie A. Lawlor, Alex Lewin, Cecilia Lindgren, Julie Marsh, Christel Middeldorp, Iona Millwood, Dennis O. Mook-Kanamori, Michel Nivard, Paul F. O'Reilly, Lyle J. Palmer, Inga Prokopenko, Alina Rodriguez, Sylvain Sebert, Ulla Sovio, Beate St Pourcain, Marie Standl, David P. Strachan, Jordi Sunyer, H. Rob Taal, Elisabeth Thiering, Carla Tiesler, Andre G. Uitterlinden, Beatriz Valcarcel, Nicole M. Warrington, Scott White, Gonneke Willemsen, Hanieh Yaghootkar, Dorret I. Boomsma, Xavier Estivill, Struan F. A. Grant, Hakon Hakonarson, Andrew T. Hattersley, Joachim Heinrich, Vincent W. V. Jaddoe, Marjo-Riitta Jarvelin, Mark I. McCarthy, Craig E. Pennell, Chris Power, Nicholas J. Timpson, Elisabeth Widen, M. Arfan Ikram, Myriam Fornage, Albert V. Smith, Sudha Seshadri, Reinhold Schmidt, Stephanie Debette, Henri A. Vrooman, Sigurdur Sigurdsson, Stefan Ropele, Laura H. Coker, W. T. Longstreth, Wiro J. Niessen, Anita L. DeStefano, Alexa Beiser, Alex P. Zijdenbos, Maksim Struchalin, Clifford R. Jack, Mike A. Nalls, Rhoda Au, Albert Hofman, Haukur Gudnason, Aad van der Lugt, Tamara B. Harris, William M. Meeks, Meike W. Vernooij, Mark A. van Buchem, Diane Catellier, Vilmundur Gudnason, B. Gwen Windham, Philip A. Wolf, Cornelia M. van Duijn, Thomas H. Mosley, Helena Schmidt, Lenore J. Launer, Monique M. B. Breteler, Charles DeCarli

  • 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),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.show moreshow less

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Author details:H. Rob Taal, Beate St Pourcain, Elisabeth Thiering, Shikta Das, Dennis O. Mook-Kanamori, Nicole M. Warrington, Marika Kaakinen, Eskil Kreiner-Moller, Jonathan P. Bradfield, Rachel M. Freathy, Frank Geller, Monica Guxens, Diana L. Cousminer, Marjan Kerkhof, Nicholas J. Timpson, M. Arfan Ikram, Lawrence J. Beilin, Klaus Bonnelykke, Jessica L. Buxton, Pimphen Charoen, Bo Lund Krogsgaard Chawes, Johan Eriksson, David M. Evans, Albert Hofman, John P. Kemp, Cecilia E. Kim, Norman Klopp, Jari Lahti, Stephen J. Lye, George McMahon, Frank D. Mentch, Martina Mueller-Nurasyid, Paul F. O'Reilly, Inga Prokopenko, Fernando Rivadeneira, Eric A. P. Steegers, Jordi Sunyer, Carla Tiesler, Hanieh Yaghootkar, Monique M. B. Breteler, Stephanie Debette, Myriam Fornage, Vilmundur Gudnason, Lenore J. Launer, Aad van der Lugt, Thomas H. Mosley, Sudha Seshadri, Albert V. Smith, Meike W. Vernooij, Alexandra I. F. Blakemore, Rosetta M. Chiavacci, Bjarke Feenstra, Julio Fernandez-Banet, Struan F. A. Grant, Anna-Liisa Hartikainen, Albert J. van der Heijden, Carmen Iniguez, Mark Lathrop, Wendy L. McArdle, Anne Molgaard, John P. Newnham, Lyle J. Palmer, Aarno Palotie, Annneli Pouta, Susan M. Ring, Ulla Sovio, Marie Standl, Andre G. Uitterlinden, H-Erich Wichmann, Nadja Hawwa Vissing, Charles DeCarli, Cornelia M. van Duijn, Mark I. McCarthy, Gerard H. Koppelman, Xavier Estivill, Andrew T. Hattersley, Mads Melbye, Hans Bisgaard, Craig E. Pennell, Elisabeth Widen, Hakon Hakonarson, George Davey Smith, Joachim Heinrich, Marjo-Riitta Jarvelin, Vincent W. V. Jaddoe, Linda S. Adair, Wei Ang, Mustafa Atalay, Toos van Beijsterveldt, Nienke Bergen, Kelly Benke, Diane J. Berry, Jonathan P. Bradfield, Pimphen Charoen, Lachlan Coin, Diana L. Cousminer, Shikta Das, Oliver S. P. Davis, Paul Elliott, David M. Evans, Bjarke Feenstra, Claudia Flexeder, Tim Frayling, Rachel M. Freathy, Romy Gaillard, Frank Geller, Maria Groen-Blokhuis, Liang-Kee Goh, Monica Guxens, Claire M. A. Haworth, Dexter Hadley, Johannes Hebebrand, Anke Hinney, Joel N. Hirschhorn, John W. Holloway, Claus Holst, Jouke Jan Hottenga, Momoko Horikoshi, Ville Huikari, Elina Hypponen, Carmen Iniguez, Marika Kaakinen, Tuomas O. Kilpelainen, Mirna Kirin, Matthew Kowgier, Hanna-Maaria Lakka, Leslie A. Lange, Debbie A. Lawlor, Terho Lehtimaki, Alex Lewin, Cecilia Lindgren, Virpi Lindi, Reedik Maggi, Julie Marsh, Christel Middeldorp, Iona Millwood, Dennis O. Mook-Kanamori, Jeffrey C. Murray, Michel Nivard, Ellen Aagaard Nohr, Ioanna Ntalla, Emily Oken, Paul F. O'Reilly, Lyle J. Palmer, Kalliope Panoutsopoulou, Jennifer Pararajasingham, Inga Prokopenko, Alina Rodriguez, Rany M. Salem, Sylvain Sebert, Niina Siitonen, Ulla Sovio, Beate St Pourcain, David P. Strachan, Jordi Sunyer, H. Rob Taal, Yik-Ying Teo, Elisabeth Thiering, Carla Tiesler, Andre G. Uitterlinden, Beatriz Valcarcel, Nicole M. Warrington, Scott White, Gonneke WillemsenORCiD, Hanieh Yaghootkar, Eleftheria Zeggini, Dorret I. Boomsma, Cyrus Cooper, Xavier Estivill, Matthew Gillman, Struan F. A. Grant, Hakon Hakonarson, Andrew T. Hattersley, Joachim Heinrich, Berthold HocherORCiDGND, Vincent W. V. Jaddoe, Marjo-Riitta Jarvelin, Timo A. Lakka, Mark I. McCarthy, Mads Melbye, Karen L. Mohlke, George V. Dedoussis, Ken K. Ong, Ewan R. Pearson, Craig E. Pennell, Thomas S. Price, Chris Power, Olli T. Raitakari, Seang-Mei Saw, Andre Scherag, Olli Simell, Thorkild I. A. Sorensen, Nicholas J. Timpson, Elisabeth Widen, James F. Wilson, Wei Ang, Toos van Beijsterveldt, Nienke Bergen, Kelly Benke, Diane J. Berry, Jonathan P. Bradfield, Pimphen Charoen, Lachlan Coin, Diana L. Cousminer, Shikta Das, Paul Elliott, David M. Evans, Tim Frayling, Rachel M. Freathy, Romy Gaillard, Maria Groen-Blokhuis, Monica Guxens, Dexter Hadley, Jouke Jan Hottenga, Ville Huikari, Elina Hypponen, Marika Kaakinen, Matthew Kowgier, Debbie A. Lawlor, Alex Lewin, Cecilia Lindgren, Julie Marsh, Christel Middeldorp, Iona Millwood, Dennis O. Mook-Kanamori, Michel Nivard, Paul F. O'Reilly, Lyle J. Palmer, Inga Prokopenko, Alina Rodriguez, Sylvain Sebert, Ulla Sovio, Beate St Pourcain, Marie Standl, David P. Strachan, Jordi Sunyer, H. Rob Taal, Elisabeth Thiering, Carla Tiesler, Andre G. Uitterlinden, Beatriz Valcarcel, Nicole M. Warrington, Scott White, Gonneke WillemsenORCiD, Hanieh Yaghootkar, Dorret I. Boomsma, Xavier Estivill, Struan F. A. Grant, Hakon Hakonarson, Andrew T. Hattersley, Joachim Heinrich, Vincent W. V. Jaddoe, Marjo-Riitta Jarvelin, Mark I. McCarthy, Craig E. Pennell, Chris Power, Nicholas J. Timpson, Elisabeth Widen, M. Arfan Ikram, Myriam Fornage, Albert V. Smith, Sudha Seshadri, Reinhold Schmidt, Stephanie Debette, Henri A. Vrooman, Sigurdur Sigurdsson, Stefan Ropele, Laura H. Coker, W. T. Longstreth, Wiro J. Niessen, Anita L. DeStefano, Alexa Beiser, Alex P. Zijdenbos, Maksim Struchalin, Clifford R. Jack, Mike A. Nalls, Rhoda Au, Albert Hofman, Haukur Gudnason, Aad van der Lugt, Tamara B. Harris, William M. Meeks, Meike W. Vernooij, Mark A. van Buchem, Diane Catellier, Vilmundur Gudnason, B. Gwen Windham, Philip A. Wolf, Cornelia M. van Duijn, Thomas H. Mosley, Helena Schmidt, Lenore J. Launer, Monique M. B. Breteler, Charles DeCarli
DOI:https://doi.org/10.1038/ng.2238
ISSN:1061-4036
Title of parent work (English):Nature genetics
Publisher:Nature Publ. Group
Place of publishing:New York
Publication type:Article
Language:English
Year of first publication:2012
Publication year:2012
Creating corporation:Cohorts Heart Aging Res Genetic Ep, Early Genetics Lifecourse Epidemio, Early Growth Genetics EGG Consorti
Release date:2017/03/26
Volume:44
Issue:5
Number of pages:9
First page:532
Last Page:+
Funding institution:Academy of Finland [104781, 120315, 129269, 1114194, 134839, 129287]; Biocentrum Helsinki; Biocenter, University of Oulu, Finland; British Heart Foundation; Canadian Institutes of Health Research [MOP 82893]; The Children's Hospital of Philadelphia; Cotswold Foundation; Darlington Trust; Dutch Asthma Foundation; Dutch Ministry of the Environment; Erasmus Medical Center Rotterdam; Erasmus University Rotterdam; European Community [HEALTH-F4-2007-201413]; Exeter National Health Service (NHS) Research and Development; Fundacio La Marato de TV3 (Televisio de Catalunya); Helmholtz Zentrum Muenchen; German Research Center for Environment and Health; Institute of Epidemiology I; Neuherberg; Instituto de Salud Carlos III [FIS PI081151, PS09/00432]; Institut fur Umweltmedizinische Forschung (IUF) Dusseldorf; Marien-Hospital Wesel; UK MRC [G0500539, G0600331, G0600705]; Municipal Health Service Rotterdam; National Health and Medical Research Council of Australia [403981, 003209]; National Public Health Institute, Helsinki, Finland; Netherlands Organisation for Scientific Research (NWO); Netherlands Organisation for Health Research and Development (ZonMw) [SPI 56-464-14192, 904-61-090, 904-61-193, 912-03-031, 480-04-004, 400-05-717]; US NHLBI [5R01HL087679-02, 1RL1MH083268-01]; US NIH [1R01HD056465-01A1]; Peninsula NIHR Clinical Research Facility; RAINE Medical Research Foundation; Rotterdam Homecare Foundation; South West NHS Research and Development; Stichting Astmabestrijding; Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR) Rotterdam; Technical University Munich; Telethon Institute for Child Health Research; UFZ-Centre for Environmental Research Leipzig-Halle; University Hospital Oulu, Finland; University of Bristol; University of Leipzig; Wellcome Trust [GR069224, 085541/Z/08/Z, WT083431MA, WT088431MA]; Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource; ZonMW [21000074]; Dutch Kidney Foundation [C08.2251]; MRC UK [G0500539, PS0476]; MRC [MRC G0800582]; Netherlands Organisation for Health Research (ZonMw) [90700303, 916.10159]
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie
Peer review:Referiert
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