Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes

Author:

Vogelezang Suzanne,Bradfield Jonathan P.,Vogelezang Suzanne,Bradfield Jonathan P.,Johansson Stefan,Stergiakouli Evie,Thiering Elisabeth,Pennell Craig E.,Ahluwalia Tarunveer S.,Karhunen Ville,Scholz Markus,Liu Xueping,Iñiguez Carmen,Raitakari Olli T.,Bacelis Jonas,Schnurr Theresia M.,Lakka Timo A.,Ntalla Ioanna,Lind Mads V.,Lauritzen Lotte,Herrala Sauli,Lin Frederick T. J.,Frithioff-Bøjsøe Christine,Beaumont Robin N.,Zafarmand Mohammed H.,Rzehak Peter,Bilbao Jose R.,Junna Nella,Vonk Judith M.,Rifas-Shiman Sheryl L.,Janjanam Vimala D.,Knol Maria J.,Ramdas Shweta,Beilin Lawrie,Bønnelykke Klaus,Casas Maribel,Eriksson Johan G.,Escribano Joaquin,Evans Tavia E.,Gehring Ulrike,Geller Frank,Grote Veit,Gruszfeld Darek,Hakonarson Hakon,Hattersley Andrew T.,Have Christian T.,Geoffrey Hayes M.,Heinrich Joachim,Helgeland Øvind,Holloway Jhon,Joro Raimo,Juodakis Julius,Knight Bridget A.,Koletzko Bert,Körner Antje,Langhendries Jean-Paul,Leinonen Jaakko T.,Lindi Virpi,Lund Morten A. V.,Lye Stephen,Melbye Mads,Michaelsen Kim F.,Morgen Camilla S.,Niinikoski Harri,Pahkala Katja,Panoutsopoulou Kalliope,Pedersen Oluf,Rivadeneira Fernando,Santa-Marina Loreto,Schaik Barbera D. C.,Scholtens Denise,Sebert Sylvain,Tamayo Ibon,Timpson Nicholas J.,Torrent Maties,Uitterlinden André G.,Vaudel Marc,Verduci Elvira,Vinding Rebecca,Vogel Mandy,Zeggini Eleftheria,Brown Christopher,Adams Hieab H. H.,Karmaus Wilfried,Hivert Marie-France,Koppelman Gerard H.,Widén Elisabeth,Fernandez-Jimenez Nora,Waldenberger Melanie,Vrijkotte Tanja G. M.,Freathy Rachel M.,Holm Jens-Christian,Lowe William L.,Grarup Niels,Hansen Torben,Dedoussis George V.,Atalay Mustafa,Nohr Ellen A.,Jacobsson Bo,Pitkänen Niina,Vrijheid Martine,Feenstra Bjarke,Kiess Wieland,Jarvelin Marjo-Riita,Bisgaard Hans,Wang C Carol,Standl Marie,McCarthy Mark I.,Pourcain Beate St,Njølstad Pål R.,Grant Struan F. A.,Felix Janine F.,Jaddoe Vincent W. V.,

Abstract

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.

Funder

Institute Development Award from the Children’s Hospital of Philadelphia

Research Development Award from the Cotswold Foundation

Children’s Hospital of Philadelphia Endowed Chair in Genomic Research

NIH

The Daniel B. Burke Endowed Chair for Diabetes Research

Netherlands Organization for Health Research and Development

European Research Council

Publisher

Springer Science and Business Media LLC

Subject

Genetics (clinical),Genetics

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