Abstract
Background: Head circumference is associated with intelligence and tracks from childhood into adulthood. Methods: We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. Results: Seven loci reached genome-wide significance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes. Conclusions: The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.
| Original language | English (US) |
|---|---|
| Article number | 124 |
| Journal | BMC Medical Genomics |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2022 |
Keywords
- Genetic correlations
- Genome-wide association study
- Head circumference
- Infancy
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
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In: BMC Medical Genomics, Vol. 15, No. 1, 124, 12.2022.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes
AU - the Early Growth Genetics Consortium
AU - Vogelezang, Suzanne
AU - Bradfield, Jonathan P.
AU - Johansson, Stefan
AU - Stergiakouli, Evie
AU - Thiering, Elisabeth
AU - Pennell, Craig E.
AU - Ahluwalia, Tarunveer S.
AU - Karhunen, Ville
AU - Scholz, Markus
AU - Liu, Xueping
AU - Iñiguez, Carmen
AU - Raitakari, Olli T.
AU - Bacelis, Jonas
AU - Schnurr, Theresia M.
AU - Lakka, Timo A.
AU - Ntalla, Ioanna
AU - Lind, Mads V.
AU - Lauritzen, Lotte
AU - Herrala, Sauli
AU - Lin, Frederick T.J.
AU - Frithioff-Bøjsøe, Christine
AU - Beaumont, Robin N.
AU - Zafarmand, Mohammed H.
AU - Rzehak, Peter
AU - Bilbao, Jose R.
AU - Junna, Nella
AU - Vonk, Judith M.
AU - Rifas-Shiman, Sheryl L.
AU - Janjanam, Vimala D.
AU - Knol, Maria J.
AU - Ramdas, Shweta
AU - Beilin, Lawrie
AU - Bønnelykke, Klaus
AU - Casas, Maribel
AU - Eriksson, Johan G.
AU - Escribano, Joaquin
AU - Evans, Tavia E.
AU - Gehring, Ulrike
AU - Geller, Frank
AU - Grote, Veit
AU - Gruszfeld, Darek
AU - Hakonarson, Hakon
AU - Hattersley, Andrew T.
AU - Have, Christian T.
AU - Geoffrey Hayes, M.
AU - Heinrich, Joachim
AU - Helgeland, Øvind
AU - Holloway, Jhon
AU - Scholtens, Denise
AU - Lowe, William L.
N1 - Funding Information: MOBA: The Norwegian Mother and Child Cohort Study was supported by grants from the European Research Council (AdG #293574), the Bergen Research Foundation (“Utilizing the Mother and Child Cohort and the Medical Birth Registry for Better Health”), Stiftelsen Kristian Gerhard Jebsen (Translational Medical Center), the University of Bergen, the Research Council of Norway (FRIPRO grant #240413), the Western Norway Regional Health Authority (Strategic Fund “Personalized Medicine for Children and Adults”, and Open Grants («Understanding infant weight biology through genomics and deep phenotyping» grant #912250), and the Norwegian Diabetes Foundation; the Research Council of Norway through its Centres of Excellence funding scheme (#262700), Better Health by Harvesting Biobanks (#229624). Funding Information: HAPO is supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases (R01-HD34242 and R01-HD34243); the National Center for Research Resources (M01-RR00048 and M01-RR00080); and the American Diabetes Association; and grants to local field centers from Diabetes UK (RD04/0002756), Kaiser Permanente Medical Center, KK Women's and Children's Hospital, Mater Mother's Hospital, Novo Nordisk, the Myre Sim Fund of the Royal College of Physicians of Edinburgh, and the Howard and Carol Bernick Family Foundation. Funding Information: EZ received funding from Wellcome Trust (098051). CSM was funded by the University of Southern Denmark. BSP is supported through funds of the Max Planck core society and the Simons Foundation (Award ID: 514787). NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 102215/2/13/2), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215-20011), the MRC Integrative Epidemiology Unit (MC_UU_12013/3) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). BSTP is funded by Max Planck Society core funds and the Simons Foundation (514787). BK received personal funding by the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG—no. 322605). RNB and RMF are funded by a Wellcome Trust and Royal Society Sir Henry Dale Fellowship, grant 104150/Z/14/Z. VK was funded by Marie Curie CAPICE EU project (European Union's Horizon 2020 research and innovation programme under grant agreement no. 721567). SFAG was financially supported by an Institute Development Award from the Children’s Hospital of Philadelphia, a Research Development Award from the Cotswold Foundation, the Daniel B. Burke Endowed Chair for Diabetes Research, the Children’s Hospital of Philadelphia Endowed Chair in Genomic Research and NIH grant R01 HD056465. NFJ received funding from Basque Dpt. of Health (SAN2018111086). HHHA was supported by ZonMW grant number 916.19.151. MHZ was supported by BBMRI-NL (CP2013-50). TGMV was supported by ZonMW (TOP 40–00812–98–11010). XL was supported by the Nordic Center of Excellence in Health-Related e-Sciences. BF was supported by the Oak Foundation and the Novo Nordisk Foundation (12955). MFH is supported by ADA Pathways to Stop Diabetes award 1-15-ACE-26. VWVJ received funding from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (ERC-2014-CoG-648916). MMcC is a Wellcome Senior Investigator and an NIHR Senior Investigator. Relevant funding support for this work comes from Wellcome (090532, 106130, 098381, 203141, 212259), NIDDK (U01-DK105535), and NIHR (NF-SI-0617-10090). Funding Information: All funding received by COPSAC is listed on www.copsac.com . The Lundbeck Foundation (Grant no R16-A1694); The Ministry of Health (Grant no 903516); Danish Council for Strategic Research (Grant no 0603-00280B) and The Capital Region Research Foundation have provided core support to the COPSAC research center. Funding Information: The Northern Finland Birth Cohort (NFBC) Research program, including the study of the NFBC 1966 and 1986 studies, received financial support from Academy of Finland (1114194, 24300796), NHLBI grant 5R01HL087679 through the STAMPEED program (1RL1MH083268-01), ENGAGE project and grant agreement HEALTH-F4-2007-201413, the Medical Research Council (grant G0500539, centre grant G0600705, PrevMetSyn), and the Wellcome Trust (project grant GR069224), UK. The program is currently being funded by the H2020-633595 DynaHEALTH action and Academy of Finland EGEA-project. Funding Information: The SKOT 1 and 2 study have their base at the Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen and was supported by grants from The Danish Directorate for Food, Fisheries and Agri Business as part of the ‘Complementary and young child feeding (CYCF)—impact on short- and long-term development and health’ project and partly by contributions from the research program ‘Governing Obesity’ by the University of Copenhagen Excellence Program for Interdisciplinary Research ( www.go.ku.dk ). Funding Information: The analyses were supported by the Research Council of Norway (grant FRIMEDBIO ES547711 to Bo Jacobsson), the March of Dimes Foundation Prematurity Research Initiative Program (grant 21-FY16-121 to Bo Jacobsson). Funding Information: Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland (JGE grant no. 129369, 129907, 135072, 129255 and 126775), the Finnish Diabetes Research Society, Samfundet Folkhälsan, Novo Nordisk Foundation, Finska Läkaresällskapet, Juho Vainio Foundation, Signe and Ane Gyllenberg Foundation, Liv och Hälsa, University of Helsinki and Ministry of Education. JTL has been supported by the Finnish Cultural Foundation. Funding Information: The INMA Menorca (MEN), Valencia (VAL) and Sabadell (SAB) cohorts were funded by grants from the Instituto de Salud Carlos III (CB06/02/0041, G03/176, FIS PI041436, PI081151, PI041705, and PS09/00432, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, and 09/02647), Fundació La Marató de TV3 (090430), Generalitat de Catalunya-CIRIT (1999SGR 00241), Conselleria de Sanitat Generalitat Valenciana, and Fundación Roger Torné. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. Funding Information: This study was supported by the National Institutes of Health (UG3OD23286, R01 HD034568, and R01 AI102960). Funding Information: The PIAMA study was funded by grants from the Dutch Asthma Foundation (grant 3.4.01.26, 3.2.06.022, 3.4.09.081 and 3.2.10.085CO), the ZON-MW Netherlands Organization for Health Research and Development (grant 912-03-031), the Stichting Astmabestrijding and the Ministry of the Environment. Genome-wide genotyping was funded by the European Commission as part of GABRIEL (A multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community) contract number 018996 under the Integrated Program LSH-2004-1.2.5-1 Post genomic approaches to understand the molecular basis of asthma aiming at a preventive or therapeutic control and a Grant from BBMRI-NL (CP 29). Funding Information: The general design of Generation RStudy is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families. The project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633595 (DynaHEALTH) and under grant agreements No 733206 (LifeCycle). Funding Information: The Exeter Family Study of Childhood Health (EFSOCH) was supported by South West NHS Research and Development, Exeter NHS Research and Development, the Darlington Trust and the Peninsula National Institute of Health Research (NIHR) Clinical Research Facility at the University of Exeter. The opinions given in this paper do not necessarily represent those of NIHR, the NHS or the Department of Health. Genotyping of the EFSOCH study samples was funded by the Welcome Trust and Royal Society grant 104150/Z/14/Z. Funding Information: The research of the CHOP study reported herein was partially supported by the Commission of the European Community, specific RTD Programme “Quality of Life and Management of Living Resources,” within the 5th Framework Programme (research grant nos. QLRT-2001-00389 and QLK1-CT-2002-30582); the 6th Framework Programme contract no. 007036 (FP6-007036); the European Union’s Seventh Framework Programme Project EarlyNutrition under grant agreement no. 289346 (FP7-289346), the Horizon 2020 research and innovation programme DYNAHEALTH (no. 633595) and the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG—no. 322605). Additional support from the German Ministry of Education and Research, Berlin (Grant Nr. 01 GI 0825) and the University of Munich Innovative Research Priority Project MC-Health is gratefully acknowledged. This manuscript does not necessarily reflect the views of the Commission and in no way anticipates the future policy in this area. The funders of this study had no role in study design, data collection, data analysis, data interpretation, decision to publish, or preparation of the manuscript. Funding Information: STRIP was supported by the Academy of Finland (grants 206374, 294834, 251360, and 275595), the Juho Vainio Foundation, the Finnish Foundation for Cardiovascular Research, the Finnish Ministry of Education and Culture, the Finnish Cultural Foundation, the Sigrid Juselius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital), the Yrjö Jahnsson Foundation, and the Turku University Foundation. Funding Information: The PANIC Study has financially been supported by grants from Ministry of Education and Culture of Finland, Ministry of Social Affairs and Health of Finland, Research Committee of the Kuopio University Hospital Catchment Area (State Research Funding), Finnish Innovation Fund Sitra, Social Insurance Institution of Finland, Finnish Cultural Foundation, Foundation for Paediatric Research, Diabetes Research Foundation in Finland, Finnish Foundation for Cardiovascular Research, Juho Vainio Foundation, Paavo Nurmi Foundation, Yrjö Jahnsson Foundation, and the city of Kuopio. The PhD students and postdoctoral researchers of The PANIC Study have financially been supported by personal grants from Program for Clinical Research and Program for Health Sciences of Doctoral School of University of Eastern Finland, Finnish Doctoral Programs in Public Health, Finnish Doctoral Program in Oral Sciences, European Commission Marie Curie Fellowship Programme, North Savo Regional Fund of Finnish Cultural Foundation, Juho Vainio Foundation, Päivikki and Sakari Sohlberg Foundation, Foundation for Paediatric Research, Diabetes Research Foundation in Finland, Finnish Foundation for Cardiovascular Research, Emil Aaltonen Foundation, Paulo Foundation, Jalmari and Rauha Ahokas Foundation, Aarne and Aili Turunen Foundation, Finnish Medical Foundation, Jenny and Antti Wihuri Foundation, Orion Foundation, Urho Känkänen Foundation, Finnish Association for the Study of Pain, Finnish Dental Society Apollonia, Northern Savo Dental Association, Health Centre Dentist Association, Finnish Female Dentists Association, Kuopio Naturalists' Society, Olvi Foundation, and the city of Kuopio. Funding Information: The GINIplus study was mainly supported for the first 3 years of the Federal Ministry for Education, Science, Research and Technology (interventional arm) and Helmholtz Zentrum Munich (former GSF) (observational arm). The 4 year, 6 year, 10 year and 15 year follow-up examinations of the GINIplus study were covered from the respective budgets of the 5 study centres (Helmholtz Zentrum Munich (former GSF), Research Institute at Marien-Hospital Wesel, LMU Munich, TU Munich and from 6 years onwards also from IUF—Leibniz Research-Institute for Environmental Medicine at the University of Düsseldorf) and a grant from the Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296). Further, the 15 year follow-up examination of the GINIplus study was supported by the Commission of the European Communities, the 7th Framework Program: MeDALL project, and as well by the companies Mead Johnson and Nestlé. The LISA study was mainly supported by grants from the Federal Ministry for Education, Science, Research and Technology and in addition from Helmholtz Zentrum Munich (former GSF), Helmholtz Centre for Environmental Research—UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef for the first 2 years. The 4 year, 6 year, 10 year and 15 year follow-up examinations of the LISA study were covered from the respective budgets of the involved partners (Helmholtz Zentrum Munich (former GSF), Helmholtz Centre for Environmental Research—UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef, IUF—Leibniz-Research Institute for Environmental Medicine at the University of Düsseldorf) and in addition by a grant from the Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296). Further, the 15-year follow-up examination of the LISA study was supported by the Commission of the European Communities, the 7th Framework Program: MeDALL project. Funding Information: The INMA-GIP cohort was funded by the Spanish Biomedical Research Center in Epidemiology and Public Health (CIBERESP) and by grants from the Instituto de Salud Carlos III (PI06/0867, PI09/00090, PI13/02187 and PI18/01142) cofunded by ERDF, “A way to make Europe”, the Basque Department of Health (Projects 2005111093, 2009111069, 2013111089, 2015111065 and 2018111086), the Provincial Government of Gipuzkoa (Projects DFG06/002, DFG08/001 and DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia and Beasain). Funding Information: LIFE-Child is funded by the Leipzig Research Center for Civilization Diseases (LIFE). LIFE is an organizational unit affiliated to the Medical Faculty of the University of Leipzig. LIFE is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by funds of the Free State of Saxony within the framework of the excellence initiative. The study was further supported by the German Research Foundation (DFG) for the CRC1052 ObesityMechanisms, project C05. Funding Information: MMcC: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. He serves on advisory panels for Pfizer, NovoNordisk, Zoe Global; has received honoraria from Merck, Pfizer, NovoNordisk and Eli Lilly; has stock options in Zoe Global; has received research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier & Takeda. Ms Receives funding from Pfizer Inc. for a project not related to this research. The other authors declare that they have no competing interests. Funding Information: SV, JFF and VWVJ designed the research and wrote the paper. SV, JFF and JPB analyzed the meta-analysis data. IN, JFF, VWVJ, GVD, KB, HB, KFM, LL, JCH, PR, VG, BK, JPL, EV, JE, DG, TAL, VL, MA, AK, WK, UG, CEP, SL, LW, OTR, KP, HN, TGMV, MM, BF, WK, and JH were responsible for the study design of an individual contributing study. JFF, VWVJ, IN, GVD, JTL, EW, TSA, KB, HB, MVL, KFM, LL, CFB, MAVL, JCH, NJT, GDS, PR, VG, BK, JPL, EV, JE, DE, TAL, MV, AK, WK, HH, SFAG, BAK, ATH, RMF, LSM, CI, MT, MV, CEP, SL, LW, HHHA, OTR, KP, HN, MM, BF, WK, JH, and MFH were responsible for the management of an individual contributing study. SV, IN, GVD, JGE, RV, KB, HB, CSM, EAN, PRN, SJ, ØH, MV, CFB, MAVL, JCH, NJT, GDS, PR, VG, BK, JPL, EV, JE, DG, TAL, VL, MA, MV, AK, WK, HH, SFAG, BAK, ATH, LSM, MC, CEP, SL, LB, TEE, OTR, KP, HN, TGMV, FG, and BF were involved in sample collection and phenotyping of an individual contributing study. FR, EZ, JGE, TSA, HB, TMS, CTH, CSM, TH, NG, PRN, SJ, ØH, MV, CFB, MAVL, OP, JCH, ES, NJT, GDS, BP, MW, TAL, MA, MS, HH, SFAG, JMV, RNB, NFJ, JRB, CEP, SL, LW, OTR, MHZ, AGU, MMcC, and TGMV genotyped the data of an individual contributing study. SV, FR, JFF, IN, KP, NJ, JTL, TSA, TMS, CTH, NG, ØH, MV, BP, PR, VL, RJ, MS, JPB, RNB, IT, NFJ, JRB, CW, MJK, NP, MHZ, XL, FG, BF, VDJ, and SLRS analyzed data of an individual contributing study. All authors provided comments and consultation regarding the analyses, interpretation of the results and manuscript. SV, JFF and VWVJ had primary responsibility for final content. All authors gave final approval of the version to be published. Funding Information: TEENAGE study has been co-financed by the European Union (European Social Fund—ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF)—Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund. This work was funded by the Wellcome Trust (098051). Funding Information: TDCOB received support from the Danish Innovation Foundation and The Region Zealand Health and Medical Research Foundation. This study was partly supported by grants from the Program Committee for Individuals, Disease and Society of the Danish Innovation Foundation (grant numbers: 0603-00484B [TARGET] and 0603-00457B [BIOCHILD]). The Novo Nordisk Foundation Center for Basic Metabolic Research, an independent Research Center at the University of Copenhagen, is partially funded by an unrestricted donation from the Novo Nordisk Foundation. Funding Information: We are grateful to the Raine Study participants and their families and we thank the Raine Study and Lions Eye Institute research staff for cohort coordination and data collection. The Raine Study acknowledges the National Health and Medical Research Council (NHMRC) for their long term contribution to funding the study over the last 29 years. The core management of the Raine Study has been funded by the University of Western Australia, Curtin University, Telethon Kids Institute, Women and Infants Research Foundation, Edith Cowan University, Murdoch University, The University of Notre Dame Australia, and the Raine Medical Research Foundation. The collection of the GWAS data for Gen2 of the Raine Study participants were supported by the Canadian Institutes of Health Research—CIHR (MOP-82893) and the National Health and Medical Research Council of Australia [grant numbers 634445, 634509, and 1021105]. The authors gratefully acknowledge the assistance of the Western Australian DNA Bank (National Health and Medical Research Council of Australia National Enabling Facility). This work was supported by resources provided by the Pawsey Supercomputing Centre with funding from the Australian Government and Government of Western Australia. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Head circumference is associated with intelligence and tracks from childhood into adulthood. Methods: We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. Results: Seven loci reached genome-wide significance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes. Conclusions: The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.
AB - Background: Head circumference is associated with intelligence and tracks from childhood into adulthood. Methods: We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. Results: Seven loci reached genome-wide significance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes. Conclusions: The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.
KW - Genetic correlations
KW - Genome-wide association study
KW - Head circumference
KW - Infancy
UR - http://www.scopus.com/inward/record.url?scp=85137679586&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85137679586&partnerID=8YFLogxK
U2 - 10.1186/s12920-022-01281-1
DO - 10.1186/s12920-022-01281-1
M3 - Article
C2 - 35659227
AN - SCOPUS:85137679586
SN - 1755-8794
VL - 15
JO - BMC Medical Genomics
JF - BMC Medical Genomics
IS - 1
M1 - 124
ER -