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

Haworth, S; Shapland, CY; Hayward, C; Prins, BP; Felix, JF; Medina-Gomez, C; Rivadeneira, F; Wang, C; Ahluwalia, TS; Vrijheid, M; et al. Haworth, S; Shapland, CY; Hayward, C; Prins, BP; Felix, JF; Medina-Gomez, C; Rivadeneira, F; Wang, C; Ahluwalia, TS; Vrijheid, M; Guxens, M; Sunyer, J; Tachmazidou, I; Walter, K; Iotchkova, V; Jackson, A; Cleal, L; Huffmann, J; Min, JL; Sass, L; Timmers, PRHJ; Al Turki, S; Anderson, CA; Anney, R; Antony, D; Artigas, MS; Ayub, M; Bala, S; Barrett, JC; Barroso, I; Beales, P; Bentham, J; Bhattacharya, S; Birney, E; Blackwood, D; Bobrow, M; Bochukova, E; Bolton, PF; Bounds, R; Boustred, C; Breen, G; Calissano, M; Carss, K; Charlton, R; Chatterjee, K; Chen, L; Ciampi, A; Cirak, S; Clapham, P; Clement, G; Coates, G; Cocca, M; Collier, DA; Cosgrove, C; Cox, T; Craddock, N; Crooks, L; Curran, S; Curtis, D; Daly, A; Danecek, P; Day, INM; Day-Williams, A; Dominiczak, A; Down, T; Du, Y; Dunham, I; Durbin, R; Edkins, S; Ekong, R; Ellis, P; Evans, DM; Farooqi, IS; Fitzpatrick, DR; Flicek, P; Floyd, J; Foley, AR; Franklin, CS; Futema, M; Gallagher, L; Gaunt, TR; Geihs, M; Geschwind, D; Greenwood, CMT; Griffin, H; Grozeva, D; Guo, X; Guo, X; Gurling, H; Hart, D; Hendricks, AE; Holmans, P; Howie, B; Huang, J; Huang, L; Hubbard, T; Humphries, SE; Hurles, ME; Hysi, P; Jackson, DK; Jamshidi, Y; Joyce, C; Karczewski, KJ; Kaye, J; Keane, T; Kemp, JP; Kennedy, K; Kent, A; Keogh, J; Khawaja, F; van Kogelenberg, M; Kolb-Kokocinski, A; Lachance, G; Langford, C; Lawson, D; Lee, I; Lek, M; Li, R; Li, Y; Liang, J; Lin, H; Liu, R; Lonnqvist, J; Lopes, LR; Lopes, M; MacArthur, DG; Mangino, M; Marchini, J; Marenne, G; Maslen, J; Mathieson, I; McCarthy, S; McGuffin, P; McIntosh, AM; McKechanie, AG; McQuillin, A; Memari, Y; Metrustry, S; Migone, N; Mitchison, HM; Moayyeri, A; Morris, A; Morris, J; Muddyman, D; Muntoni, F; Northstone, K; O'Donovan, MC; O'Rahilly, S; Onoufriadis, A; Oualkacha, K; Owen, MJ; Palotie, A; Panoutsopoulou, K; Parker, V; Parr, JR; Paternoster, L; Paunio, T; Payne, F; Payne, SJ; Perry, JRB; Pietilainen, O; Plagnol, V; Pollitt, RC; Porteous, DJ; Povey, S; Quail, MA; Quaye, L; Raymond, FL; Rehnstrom, K; Richards, JB; Ridout, CK; Ring, S; Ritchie, GRS; Roberts, N; Robinson, RL; Savage, DB; Scambler, P; Schiffels, S; Schmidts, M; Schoenmakers, N; Scott, RH; Semple, RK; Serra, E; Sharp, SI; Shaw, A; Shihab, HA; Shin, S-Y; Skuse, D; Small, KS; Smee, C; Smith, BH; Soranzo, N; Southam, L; Spasic-Boskovic, O; Spector, TD; St Clair, D; Stalker, J; Stevens, E; Sun, J; Surdulescu, G; Suvisaari, J; Syrris, P; Taylor, R; Tian, J; Tobin, MD; Valdes, AM; Vandersteen, AM; Vijayarangakannan, P; Visscher, PM; Wain, LV; Walters, JTR; Wang, G; Wang, J; Wang, Y; Ward, K; Wheeler, E; Whyte, T; Williams, HJ; Williamson, KA; Wilson, C; Wilson, SG; Wong, K; Xu, C; Yang, J; Zhang, F; Zhang, P; Zheng, H-F; Smith, GD; Fisher, SE; Wilson, JF; Cole, TJ; Fernandez-Orth, D; Bonnelykke, K; Bisgaard, H; Pennell, CE; Jaddoe, VWV; Dedoussis, G; Timpson, N; Zeggini, E; Vitart, V; St Pourcain, B; UK10K Consortium, (2019) Low-frequency variation in TP53 has large effects on head circumference and intracranial volume. NATURE COMMUNICATIONS, 10. p. 357. ISSN 2041-1723 https://doi.org/10.1038/s41467-018-07863-x
SGUL Authors: Jamshidi, Yalda

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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.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2019
Keywords: MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: NATURE COMMUNICATIONS
ISSN: 2041-1723
Dates:
DateEvent
21 January 2019Published
12 November 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Web of Science ID: WOS:000456164800014
URI: http://openaccess.sgul.ac.uk/id/eprint/110684
Publisher's version: https://doi.org/10.1038/s41467-018-07863-x

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