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 language | English (US) |
---|---|
Pages (from-to) | 532-538 |
Number of pages | 7 |
Journal | Nature genetics |
Volume | 44 |
Issue number | 5 |
DOIs | |
State | Published - Apr 2012 |
Externally published | Yes |
ASJC Scopus subject areas
- Genetics
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In: Nature genetics, Vol. 44, No. 5, 04.2012, p. 532-538.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Common variants at 12q15 and 12q24 are associated with infant head circumference
AU - Rob Taal, H.
AU - St Pourcain, Beate
AU - Thiering, Elisabeth
AU - Das, Shikta
AU - Mook-Kanamori, Dennis O.
AU - Warrington, Nicole M.
AU - Kaakinen, Marika
AU - Kreiner-Møller, Eskil
AU - Bradfield, Jonathan P.
AU - Freathy, Rachel M.
AU - Geller, Frank
AU - Guxens, Mònica
AU - Cousminer, Diana L.
AU - Kerkhof, Marjan
AU - Timpson, Nicholas J.
AU - Ikram, M. Arfan
AU - Beilin, Lawrence J.
AU - Bønnelykke, Klaus
AU - Buxton, Jessica L.
AU - Charoen, Pimphen
AU - Chawes, Bo Lund Krogsgaard
AU - Eriksson, Johan
AU - Evans, David M.
AU - Hofman, Albert
AU - Kemp, John P.
AU - Kim, Cecilia E.
AU - Klopp, Norman
AU - Lahti, Jari
AU - Lye, Stephen J.
AU - Mcmahon, George
AU - Mentch, Frank D.
AU - Müller-Nurasyid, Martina
AU - O'reilly, Paul F.
AU - Prokopenko, Inga
AU - Rivadeneira, Fernando
AU - Steegers, Eric A.P.
AU - Sunyer, Jordi
AU - Tiesler, Carla
AU - Yaghootkar, Hanieh
AU - Fornage, Myriam
AU - Smith, Albert V.
AU - Seshadri, Sudha
AU - Schmidt, Reinhold
AU - Debette, Stéphanie
AU - Vrooman, Henri A.
AU - Sigurdsson, Sigurdur
AU - Ropele, Stefan
AU - Coker, Laura H.
AU - Longstreth, W. T.
AU - Niessen, Wiro J.
AU - Destefano, Anita L.
AU - Beiser, Alexa
AU - Zijdenbos, Alex P.
AU - Struchalin, Maksim
AU - Jack, Clifford R.
AU - Nalls, Mike A.
AU - Au, Rhoda
AU - Gudnason, Haukur
AU - Van Der Lugt, Aad
AU - Harris, Tamara B.
AU - Meeks, William M.
AU - Vernooij, Meike W.
AU - Van Buchem, Mark A.
AU - Catellier, Diane
AU - Gudnason, Vilmundur
AU - Windham, B. Gwen
AU - Wolf, Philip A.
AU - Van Duijn, Cornelia M.
AU - Mosley, Thomas H.
AU - Schmidt, Helena
AU - Launer, Lenore J.
AU - Breteler, Monique M.B.
AU - Ang, Wei
AU - Van Beijsterveldt, Toos
AU - Bergen, Nienke
AU - Benke, Kelly
AU - Berry, Diane
AU - Coin, Lachlan
AU - Elliott, Paul
AU - Frayling, Tim
AU - Gaillard, Romy
AU - Groen-Blokhuis, Maria
AU - Hadley, Dexter
AU - Hottenga, Jouke Jan
AU - Huikari, Ville
AU - Hypponen, Elina
AU - Kowgier, Matthew
AU - Lawlor, Debbie A.
AU - Lewin, Alex
AU - Lindgren, Cecilia
AU - Marsh, Julie
AU - Middeldorp, Christel
AU - Millwood, Iona
AU - Nivard, Michel
AU - Palmer, Lyle J.
AU - Rodriguez, Alina
AU - Sebert, Sylvain
AU - Sovio, Ulla
AU - Standl, Marie
AU - Strachan, David P.
AU - Rob Taal, H.
AU - Uitterlinden, Andre G.
AU - Valcárcel, Beatriz
AU - White, Scott
AU - Willemsen, Gonneke
AU - Boomsma, Dorret I.
AU - Estivill, Xavier
AU - Grant, Struan F.A.
AU - Hattersley, Andrew T.
AU - Heinrich, Joachim
AU - Jaddoe, Vincent W.V.
AU - Jarvelin, Marjo Riitta
AU - Mccarthy, Mark I.
AU - Pennell, Craig E.
AU - Power, Chris
AU - Widen, Elisabeth
AU - Blakemore, Alexandra I.F.
AU - Chiavacci, Rosetta M.
AU - Feenstra, Bjarke
AU - Fernandez-Banet, Julio
AU - Hartikainen, Anna Liisa
AU - Van Der Heijden, Albert J.
AU - Iñiguez, Carmen
AU - Lathrop, Mark
AU - Mcardle, Wendy L.
AU - Mølgaard, Anne
AU - Newnham, John P.
AU - Palotie, Aarno
AU - Pouta, Annneli
AU - Ring, Susan M.
AU - Wichmann, H. Erich
AU - Vissing, Nadja Hawwa
AU - Decarli, Charles
AU - Koppelman, Gerard H.
AU - Melbye, Mads
AU - Bisgaard, Hans
AU - Hakonarson, Hakon
AU - Smith, George Davey
AU - Adair, Linda S.
AU - Atalay, Mustafa
AU - Davis, Oliver S.P.
AU - Flexeder, Claudia
AU - Goh, Liang Kee
AU - Haworth, Claire M.A.
AU - Hedebrand, Johannes
AU - Hinney, Anke
AU - Hirschhorn, Joel N.
AU - Holloway, John W.
AU - Holst, Claus
AU - Horikoshi, Momoko
AU - Kilpeläinen, Tuomas O.
AU - Kirin, Mirna
AU - Lakka, Hanna Maaria
AU - Lange, Leslie A.
AU - Lehtimäki, Terho
AU - Lindi, Virpi
AU - Maggi, Reedik
AU - Murray, Jeffrey C.
AU - Nohr, Ellen Aagaard
AU - Ntalla, Ioanna
AU - Oken, Emily
AU - Panoutsopoulou, Kalliope
AU - Pararajasingham, Jennifer
AU - Salem, Rany M.
AU - Siitonen, Niina
AU - Rob Taal, H.
AU - Teo, Yik Ying
AU - Zeggini, Eleftheria
AU - Cooper, Cyrus
AU - Gillman, Matthew
AU - Hocher, Berthold
AU - Lakka, Timo A.
AU - Mohlke, Karen L.
AU - Dedoussis, George V.
AU - Ong, Ken K.
AU - Pearson, Ewan R.
AU - Price, Thomas S.
AU - Raitakari, Olli T.
AU - Saw, Seang Mei
AU - Scherag, Andre
AU - Simell, Olli
AU - Sørensen, Thorkild I.A.
AU - Wilson, James F.
N1 - Funding Information: We thank A. Sayers for helpful discussions with respect to the conducted mediation analysis. Major funding for the research in this paper is from the Academy of Finland (project grants 104781, 120315, 129269, 1114194, 134839, 129287 and Center of Excellence in Complex Disease Genetics); Biocentrum Helsinki; Biocenter, University of Oulu, Finland; the British Heart Foundation; the Canadian Institutes of Health Research (grant MOP 82893); The Children’s Hospital of Philadelphia (Institute Development Award); the Cotswold Foundation (Research Development Award); the Darlington Trust; the Dutch Asthma Foundation; the Dutch Ministry of the Environment; Erasmus Medical Center Rotterdam; Erasmus University Rotterdam; The European Community’s Seventh Framework Programme (FP7/2007-2013), ENGAGE project and grant agreement HEALTH-F4-2007-201413; Exeter National Health Service (NHS) Research and Development; Fundació La Marató de TV3 (Televisió de Catalunya); Helmholtz Zentrum Muenchen, the German Research Center for Environment and Health, Institute of Epidemiology I, Neuherberg; Instituto de Salud Carlos III (FIS PI081151 and PS09/00432); Institut für Umweltmedizinische Forschung (IUF) Düsseldorf; Marien-Hospital Wesel; the UK MRC (G0500539, G0600331, PrevMetSyn/Salve/MRC and G0600705); the Municipal Health Service Rotterdam; the National Health and Medical Research Council of Australia (403981 and 003209); the National Public Health Institute, Helsinki, Finland; the Netherlands Organisation for Scientific Research (NWO) and the Netherlands Organisation for Health Research and Development (ZonMw) (grants SPI 56-464-14192, 904-61-090, 904-61-193, 912-03-031, 480-04-004 and 400-05-717); the US NHLBI (grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01)); the US NIH (grant 1R01HD056465-01A1); the Peninsula NIHR Clinical Research Facility; the RAINE Medical Research Foundation; the Rotterdam Homecare Foundation; South West NHS Research and Development; Stichting Astmabestrijding; Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR) Rotterdam; Technical University Munich; the Telethon Institute for Child Health Research; UFZ–Centre for Environmental Research Leipzig–Halle; University Hospital Oulu, Finland; University of Bristol; University of Leipzig; the Wellcome Trust (project grant GR069224); the Western Australian DNA Bank; the Western Australian Genetic Epidemiology Resource and ZonMW (grant 21000074). Data exchange and deposition has been facilitated by the SIMBioMS platform. Personal funding was provided by the Dutch Kidney Foundation (C08.2251 to H.R.T.), the MRC UK (G0500539, PrevMetSyn and PS0476 to S. Das), a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust grant 085541/Z/08/Z to R.M.F.), a MRC New Investigator Award (MRC G0800582 to D.M.E.) and Wellcome Trust 4-year PhD studentships (WT083431MA to J.P.K. and WT088431MA to J.L.B.). I.P. and J.F.-B. are in part supported by the European Community’s ENGAGE grant HEALTH-F4-2007-201413, A.T.H. is employed as a core member of the Peninsula NIHR Clinical Research Facility and V.W.V.J. is funded by the Netherlands Organisation for Health Research (ZonMw 90700303 and 916.10159). Detailed acknowledgments by study are given in the Supplementary Note.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84860324077&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860324077&partnerID=8YFLogxK
U2 - 10.1038/ng.2238
DO - 10.1038/ng.2238
M3 - Article
C2 - 22504419
AN - SCOPUS:84860324077
SN - 1061-4036
VL - 44
SP - 532
EP - 538
JO - Nature genetics
JF - Nature genetics
IS - 5
ER -