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

Nature Communications, ISSN: 2041-1723, Vol: 10, Issue: 1, Page: 357
2019
  • 23
    Citations
  • 0
    Usage
  • 104
    Captures
  • 3
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    23
  • Captures
    104
  • Mentions
    3
    • News Mentions
      2
      • 2
    • Blog Mentions
      1
      • 1

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Genes with Large Effect on Head and Brain Size Discovered

Researchers report genetic influences on head circumference remain stable during development and are correlated with genetic factors which contribute to intracranial volume.

Article Description

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.

Bibliographic Details

Simon Haworth; Chin Yang Shapland; Caroline Hayward; Bram P. Prins; Janine F. Felix; Carolina Medina-Gomez; Fernando Rivadeneira; Carol Wang; Tarunveer S. Ahluwalia; Martine Vrijheid; Mònica Guxens; Jordi Sunyer; Ioanna Tachmazidou; Klaudia Walter; Valentina Iotchkova; Andrew 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 Bochukova; Patrick F. Bolton; Rebecca Bounds; Chris Boustred; Gerome Breen; Mattia Calissano; Keren Carss; Ruth Charlton; Krishna Chatterjee; Lu Chen; Antonio Ciampi; Sebahattin Cirak; Peter Clapham; Gail Clement; Guy Coates; Massimiliano Cocca; David A. Collier; Catherine Cosgrove; Tony Cox; Nick Craddock; Lucy Crooks; Sarah Curran; David Curtis; Allan Daly; Petr Danecek; Ian N. M. Day; Aaron Day-Williams; Anna Dominiczak; Thomas Down; Yuanping Du; Ian Dunham; Richard Durbin; Sarah Edkins; Rosemary Ekong; Peter Ellis; David M. Evans; I. Sadaf Farooqi; David R. 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; Liren Huang; Tim Hubbard; Steve E. Humphries; Matthew E. Hurles; Pirro Hysi; David K. Jackson; Yalda Jamshidi; Chris Joyce; Konrad J. Karczewski; Jane Kaye; Thomas Keane; John P. Kemp; Karen Kennedy; Alastair Kent; Julia Keogh; Farrah Khawaja; Margriet van Kogelenberg; Anja Kolb-Kokocinski; Genevieve Lachance; Cordelia Langford; Daniel Lawson; Irene Lee; Monkol Lek; Rui Li; Yingrui Li; Jieqin Liang; Hong Lin; Ryan Liu; Jouko Lönnqvist; Luis 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 Morris; James Morris; Dawn Muddyman; Francesco Muntoni; Kate Northstone; Michael C. O’Donovan; Stephen O’Rahilly; Alexandros Onoufriadis; Karim Oualkacha; Michael J. Owen; Aarno Palotie; Kalliope Panoutsopoulou; Victoria Parker; Jeremy R. Parr; Lavinia Paternoster; Tiina Paunio; Felicity Payne; Stewart J. Payne; John R. B. Perry; Olli Pietilainen; 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 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 Spasic-Boskovic; 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 T. R. Walters; Guangbiao Wang; Jun Wang; Yu Wang; Kirsten Ward; Eleanor Wheeler; Tamieka Whyte; Hywel J. 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 J. Cole; Dietmar Fernandez-Orth; Klaus Bønnelykke; Hans Bisgaard; Craig E. Pennell; Vincent W. V. Jaddoe; George Dedoussis; Nicholas Timpson; Eleftheria Zeggini; Veronique Vitart; Beate St Pourcain

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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