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

by Wang, Carol , Beate St Pourcain , Haworth, Simon , Cleal, Louise , Iotchkova, Valentina , Vrijheid, Martine , Zeggini, Eleftheria , Uk10k Consortium , Chin Yang Shapland , Pennell, Craig E , Vitart, Veronique , Fisher, Simon E , Rivadeneira, Fernando , Min, Josine L , Sunyer, Jordi , Timpson, Nicholas J , L rke Sass , Jaddoe, Vincent W V , Huffmann, Jennifer , Cole, Tim J , Ahluwalia, Tarunveer S , Walter, Klaudia , Bisgaard, Hans , Medina-Gomez, Carolina , Fernandez-Orth, Dietmar , Paul R H J Timmers , Jackson, Andrew , M nica Guxens , George Davey Smith , Felix, Janine F , Klaus B nnelykke , Prins, Bram P , Dedoussis, George , Wilson, James F , Hayward, Caroline , Tachmazidou, Ioanna

in Alleles / Children / Gene frequency / Genetic diversity / Genetics / Hominids / p53 Protein / Skull

2018

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

in Alleles / Children / Gene frequency / Genetic diversity / Genetics / Hominids / p53 Protein / Skull

2018

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

in Alleles / Children / Gene frequency / Genetic diversity / Genetics / Hominids / p53 Protein / Skull

2018

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Paper

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

Wang, Carol,

Beate St Pourcain,

Haworth, Simon,

Cleal, Louise,

Iotchkova, Valentina,

Vrijheid, Martine,

Zeggini, Eleftheria,

Uk10k Consortium,

Chin Yang Shapland,

Pennell, Craig E,

Vitart, Veronique,

Fisher, Simon E,

Rivadeneira, Fernando,

Min, Josine L,

Sunyer, Jordi,

Timpson, Nicholas J,

L rke Sass,

Jaddoe, Vincent W V,

Huffmann, Jennifer,

Cole, Tim J,

Ahluwalia, Tarunveer S,

Walter, Klaudia,

Bisgaard, Hans,

Medina-Gomez, Carolina,

Fernandez-Orth, Dietmar,

Paul R H J Timmers,

Jackson, Andrew,

M nica Guxens,

George Davey Smith,

Felix, Janine F,

Klaus B nnelykke,

Prins, Bram P,

Dedoussis, George,

Wilson, James F,

Hayward, Caroline,

Tachmazidou, Ioanna

2018

Overview

Cranial growth and development affects the closely related traits of head circumference (HC) and intracranial volume (ICV). 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.

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Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory

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