Portal de Periódicos da CAPES

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-018-07863-x

2041-1723

Simon Haworth, Chin Yang Shapland, Caroline Hayward, Bram P. Prins, Janine F. Felix, Carolina Medina‐Gómez, Fernando Rivadeneira, Carol A. Wang, Tarunveer S. Ahluwalia, Martine Vrijheid, Mònica Guxens, Jordi Sunyer, Ioanna Tachmazidou, Klaudia Walter, Valentina Iotchkova, Andrew P. Jackson, Louise Cleal, Jennifer Huffmann, Josine L. Min, Lærke Sass, Paul R. H. J. Timmers, Saeed Al Turki, Carl A. Anderson, Richard Anney, Dinu Antony, María Soler Artigas, Muhammad Ayub, Senduran Bala, Jeffrey C. Barrett, Inês Barroso, Phil Beales, Jamie Bentham, Shoumo Bhattacharya, Ewan Birney, Douglas Blackwood, Martin Bobrow, Elena G. Bochukova, Patrick Bolton, Rebecca Bounds, Chris Boustred, Gerome Breen, Mattia Calissano, Keren Carss, Ruth Charlton, Krishna Chatterjee, Lu Chen, Antonio Ciampi, Sebahattin Çırak, Peter Clapham, Gail Clement, Guy Coates, Massimiliano Cocca, David Collier, Catherine Cosgrove, Tony Cox, Nick Craddock, Lucy Crooks, Sarah Curran, David Curtis, Allan Daly, Petr Danecek, Ian N. M. Day, Aaron G. Day‐Williams, Anna F. Dominiczak, Thomas A. Down, Yuanping Du, Ian Dunham, Richard Durbin, Sarah Edkins, Rosemary Ekong, Peter Ellis, David M. Evans, I. Sadaf Farooqi, David Fitzpatrick, Paul Flicek, James Floyd, A. Reghan Foley, Christopher S. Franklin, Marta Futema, Louise Gallagher, Tom R. Gaunt, Matthias Geihs, Daniel Geschwind, Celia M.T. Greenwood, Heather Griffin, Detelina Grozeva, Xiaosen Guo, Xueqin Guo, Hugh Gurling, Deborah Hart, Audrey E. Hendricks, Peter Holmans, Bryan Howie, Jie Huang, Jie Huang, Tim Hubbard, Steve E. Humphries, Matthew E. Hurles, Pirro G. Hysi, David K. Jackson, Yalda Jamshidi, Christopher Joyce, Konrad J. Karczewski, Jane Kaye, Thomas Keane, John P. Kemp, Karen L. Kennedy, Alastair Kent, Julia M. Keogh, Farrah Khawaja, Margriet van Kogelenberg, Anja Kolb‐Kokocinski, Geneviève Lachance, Cordelia Langford, Daniel J. Lawson, Irene Lee, Monkol Lek, Rui Li, Yingrui Li, Jieqin Liang, Hong Lin, Ryan Liu, Jouko Lönnqvist, Luís R. Lopes, Margarida Lopes, Daniel G. MacArthur, Massimo Mangino, Jonathan Marchini, Gaëlle Marenne, John Maslen, Iain Mathieson, Shane McCarthy, Peter McGuffin, Andrew M. McIntosh, Andrew G. McKechanie, Andrew McQuillin, Yasin Memari, Sarah Metrustry, Nicola Migone, Hannah M. Mitchison, Alireza Moayyeri, Andrew D. Morris, James Morris, Dawn Muddyman, Francesco Muntoni, Kate Northstone, Michael O’Donovan, Stephen O’Rahilly, Alexandros Onoufriadis, Karim Oualkacha, Michael J. Owen, Aarno Palotie, Kalliope Panoutsopoulou, Victoria Parker, Jeremy Parr, Lavinia Paternoster, Tiina Paunio, Felicity Payne, Stewart J. Payne, John R. B. Perry, Olli Pietiläinen, Vincent Plagnol, Rebecca C. Pollitt, David J. Porteous, Sue Povey, Michael A. Quail, Lydia Quaye, F. Lucy Raymond, Karola Rehnström, J. Brent Richards, Cheryl K. Ridout, Susan M. Ring, Graham R. S. Ritchie, Nicola Roberts, Rachel L. Robinson, David B. Savage, Peter Scambler, Stephan Schiffels, Miriam Schmidts, Nadia Schoenmakers, Richard H. Scott, Robert K. Semple, Eva Serra, Sally I. Sharp, Adam Shaw, Hashem A. Shihab, So–Youn Shin, David Skuse, Kerrin S. Small, Carol Smee, Blair H. Smith, Nicole Soranzo, Lorraine Southam, Olivera Spasić-Bošković, Timothy D. Spector, David St Clair, Jim Stalker, Elizabeth Stevens, Jianping Sun, Gabriela Surdulescu, Jaana Suvisaari, Petros Syrris, Rohan Taylor, Jing Tian, Martin D. Tobin, Ana M. Valdes, Anthony M. Vandersteen, Parthiban Vijayarangakannan, Peter M. Visscher, Louise V. Wain, James Walters, Guangbiao Wang, Jun Wang, Yu Wang, Kirsten Ward, Eleanor Wheeler, Tamieka Whyte, Hywel Williams, Kathleen A. Williamson, Crispian Wilson, Scott G. Wilson, Kim Wong, Changjiang Xu, Jian Yang, Feng Zhang, Pingbo Zhang, Hou‐Feng Zheng, George Davey Smith, Simon E. Fisher, James F. Wilson, Tim Cole, Dietmar Fernández‐Orth, Klaus Bønnelykke, Hans Bisgaard, Craig E. Pennell, Vincent W. V. Jaddoe, George Dedoussis, Nicholas J. Timpson, Eleftheria Zeggini, Véronique Vitart, Beaté St Pourcain,

Genomics and Chromatin Dynamics

Abstract Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53 , with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.