Low-frequency variation in TP53 has large effects on head circumference and intracranial volume
journal contribution
posted on 2025-05-09, 18:58 authored by Simon Haworth, Chin Yang Shapland, Monica Guxens, Y J, C J, KJ K, J K, T K, JP K, K k, F K, Jordi Sunyer, M v, A K, G L, C L, D L, I l, M L, R L, Y L, J L, Ioanna Tachmazidou, H L, LR L, DG M, M M, G M, J M, Klaudia Walter, I M, P M, AM M, AG M, A M, Y M, S M, N M, HM m, Valentina Iotchkova, D M, F M, K N, MC O, S O, A O, K O, Andrew Jackson, MJ O, A P, K P, V P, JR P, L P, T P, F P, SJ P, JRB P, Louise Cleal, O p, RC P, DJ P, S P, MA Q, L Q, FL R, K R, JB R, Jennifer Huffmann, CK R, S R, GRS R, N R, RL R, DB S, S S, M S, Josine L. Min, RH S, RK S, SI S, A S, HA S, S-Y S, KS S, C S, Laerke Sass, BH S, N S, L S, O S, TD S, D S, J S, E S, G S, Caroline Hayward, Paul R. H. J. Timmers, J s, P S, R T, J T, MD T, AM V, P V, PM V, LV W, S Al, JTR W, G W, J W, Y W, K W, E W, T W, HJ W, KA W, C W, CA A, SG W, C X, J Y, F Z, P Z, H-F Z, GD S, SE F, JF W, R A, TJ C, D F, K B, H B, Craig PennellCraig Pennell, VWV J, G D, N Ti, E Z, V V, D A, B S, MS A, M A, JC B, I B, Bram P. Prins, P B, J B, S B, D B, M B, E B, PF B, R B, C B, Janine F. Felix, G B, M C, R C, K C, L C, A Ci, S C, P C, G C, Carolina Medina-Gomez, DA C, C C, T C, N C, D C, Fernando Rivadeneira, P D, INM D, A D, T D, Y D, I D, R D, S E, R E, Aiyun WangAiyun Wang, P E, DM E, IS F, DR F, P F, J F, AR F, CS F, M F, L G, Tarunveer S. Ahluwalia, TR G, M G, CMT G, D G, X G, H G, D H, Martine Vrijheid, AE H, B H, J H, L h, T H, SE H, ME H, P H, DK JCranial 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.
History
Journal title
Nature CommunicationsVolume
10Issue
1Article number
357Publisher
Nature Publishing GroupLanguage
- en, English
