TY - JOUR
T1 - Low-frequency variation in TP53 has large effects on head circumference and intracranial volume
AU - UK10K Consortium
AU - Haworth, Simon
AU - Shapland, Chin Yang
AU - Hayward, Caroline
AU - Prins, Bram P.
AU - Felix, Janine F.
AU - Medina-Gomez, Carolina
AU - Rivadeneira, Fernando
AU - Wang, Carol
AU - Ahluwalia, Tarunveer S.
AU - Vrijheid, Martine
AU - Guxens, Mònica
AU - Sunyer, Jordi
AU - Tachmazidou, Ioanna
AU - Walter, Klaudia
AU - Iotchkova, Valentina
AU - Jackson, Andrew
AU - Cleal, Louise
AU - Huffmann, Jennifer
AU - Min, Josine L.
AU - Sass, Lærke
AU - Timmers, Paul R.H.J.
AU - Turki, Saeed Al
AU - Anderson, Carl A.
AU - Anney, Richard
AU - Antony, Dinu
AU - Artigas, María Soler
AU - Ayub, Muhammad
AU - Bala, Senduran
AU - Barrett, Jeffrey C.
AU - Barroso, Inês
AU - Beales, Phil
AU - Bentham, Jamie
AU - Bhattacharya, Shoumo
AU - Birney, Ewan
AU - Blackwood, Douglas
AU - Bobrow, Martin
AU - Bochukova, Elena
AU - Bolton, Patrick F.
AU - Bounds, Rebecca
AU - Boustred, Chris
AU - Collier, David A.
AU - Curran, Sarah
AU - Hubbard, Tim
AU - Hysi, Pirro
AU - Lachance, Genevieve
AU - McGuffin, Peter
AU - Metrustry, Sarah
AU - Moayyeri, Alireza
AU - Quaye, Lydia
AU - Valdes, Ana M.
AU - Breen, Gerome
PY - 2020/1/21
Y1 - 2020/1/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060231664&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-07863-x
DO - 10.1038/s41467-018-07863-x
M3 - Article
C2 - 30664637
AN - SCOPUS:85060231664
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 357
ER -