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-Møller, Jonathan P. Bradfield, Rachel M. Freathy, Frank Geller, Mònica Guxens, Diana L. Cousminer, Marjan Kerkhof, Nicholas J. Timpson, M. Arfan Ikram, Lawrence J. Beilin, Klaus Bønnelykke, Jessica L. Buxton, Pimphen CharoenBo 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 Müller-Nurasyid, Paul F. O'reilly, Inga Prokopenko, Fernando Rivadeneira, Eric A.P. Steegers, Jordi Sunyer, Carla Tiesler, Hanieh Yaghootkar, Myriam Fornage, Albert V. Smith, Sudha Seshadri, Reinhold Schmidt, Stéphanie 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, 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, Wei Ang, Toos Van Beijsterveldt, Nienke Bergen, Kelly Benke, Diane Berry, Lachlan Coin, Paul Elliott, Tim Frayling, Romy Gaillard, Maria Groen-Blokhuis, Dexter Hadley, Jouke Jan Hottenga, Ville Huikari, Elina Hypponen, Matthew Kowgier, Debbie A. Lawlor, Alex Lewin, Cecilia Lindgren, Julie Marsh, Christel Middeldorp, Iona Millwood, Michel Nivard, Lyle J. Palmer, Alina Rodriguez, Sylvain Sebert, Ulla Sovio, Marie Standl, David P. Strachan, H. Rob Taal, Andre G. Uitterlinden, Beatriz Valcárcel, Scott White, Gonneke Willemsen, Dorret I. Boomsma, Xavier Estivill, Struan F.A. Grant, Andrew T. Hattersley, Joachim Heinrich, Vincent W.V. Jaddoe, Marjo Riitta Jarvelin, Mark I. Mccarthy, Craig E. Pennell, Chris Power, Elisabeth Widen, Alexandra I.F. Blakemore, Rosetta M. Chiavacci, Bjarke Feenstra, Julio Fernandez-Banet, Anna Liisa Hartikainen, Albert J. Van Der Heijden, Carmen Iñiguez, Mark Lathrop, Wendy L. Mcardle, Anne Mølgaard, John P. Newnham, Aarno Palotie, Annneli Pouta, Susan M. Ring, H. Erich Wichmann, Nadja Hawwa Vissing, Charles Decarli, Gerard H. Koppelman, Mads Melbye, Hans Bisgaard, Hakon Hakonarson, George Davey Smith, Linda S. Adair, Mustafa Atalay, Oliver S.P. Davis, Claudia Flexeder, Liang Kee Goh, Claire M.A. Haworth, Johannes Hedebrand, Anke Hinney, Joel N. Hirschhorn, John W. Holloway, Claus Holst, Momoko Horikoshi, Tuomas O. Kilpeläinen, Mirna Kirin, Hanna Maaria Lakka, Leslie A. Lange, Terho Lehtimäki, Virpi Lindi, Reedik Maggi, Jeffrey C. Murray, Ellen Aagaard Nohr, Ioanna Ntalla, Emily Oken, Kalliope Panoutsopoulou, Jennifer Pararajasingham, Rany M. Salem, Niina Siitonen, H. Rob Taal, Yik Ying Teo, Eleftheria Zeggini, Cyrus Cooper, Matthew Gillman, Berthold Hocher, Timo A. Lakka, Karen L. Mohlke, George V. Dedoussis, Ken K. Ong, Ewan R. Pearson, Thomas S. Price, Olli T. Raitakari, Seang Mei Saw, Andre Scherag, Olli Simell, Thorkild I.A. Sørensen, James F. Wilson

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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 × 10-9) and rs1042725 on chromosome 12q15 (P = 2.8 × 10-10) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10 -7 for rs7980687 and P = 1.3 × 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 × 10-6). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.

Original languageEnglish (US)
Pages (from-to)532-538
Number of pages7
JournalNature genetics
Volume44
Issue number5
DOIs
StatePublished - Apr 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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