Low-frequency variation in TP53 has large effects on head circumference and intracranial volume
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 bot...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2019
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| _version_ | 1797078849058504704 |
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| author | 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 Smith, G Fisher, SE Wilson, JF Cole, TJ Fernandez-Orth, D Bønnelykke, K Bisgaard, H Pennell, CE Jaddoe, VWV Dedoussis, G Timpson, N Zeggini, E Vitart, V St Pourcain, B UK10K consortium Bhattacharya, S |
| author_facet | 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 Smith, G Fisher, SE Wilson, JF Cole, TJ Fernandez-Orth, D Bønnelykke, K Bisgaard, H Pennell, CE Jaddoe, VWV Dedoussis, G Timpson, N Zeggini, E Vitart, V St Pourcain, B UK10K consortium Bhattacharya, S |
| author_sort | Haworth, S |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T00:37:24Z |
| format | Journal article |
| id | oxford-uuid:81e58373-b2e7-4cc8-b3cf-be159d759f08 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:37:24Z |
| publishDate | 2019 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:81e58373-b2e7-4cc8-b3cf-be159d759f082022-03-26T21:33:32ZLow-frequency variation in TP53 has large effects on head circumference and intracranial volumeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:81e58373-b2e7-4cc8-b3cf-be159d759f08EnglishSymplectic Elements at OxfordNature Research2019Haworth, SShapland, CYHayward, CPrins, BPFelix, JFMedina-Gomez, CRivadeneira, FWang, CAhluwalia, TSVrijheid, MGuxens, MSunyer, JTachmazidou, IWalter, KIotchkova, VJackson, ACleal, LHuffmann, JMin, JLSass, LTimmers, PRHJSmith, GFisher, SEWilson, JFCole, TJFernandez-Orth, DBønnelykke, KBisgaard, HPennell, CEJaddoe, VWVDedoussis, GTimpson, NZeggini, EVitart, VSt Pourcain, BUK10K consortiumBhattacharya, SCranial 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. |
| spellingShingle | 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 Smith, G Fisher, SE Wilson, JF Cole, TJ Fernandez-Orth, D Bønnelykke, K Bisgaard, H Pennell, CE Jaddoe, VWV Dedoussis, G Timpson, N Zeggini, E Vitart, V St Pourcain, B UK10K consortium Bhattacharya, S Low-frequency variation in TP53 has large effects on head circumference and intracranial volume |
| title | Low-frequency variation in TP53 has large effects on head circumference and intracranial volume |
| title_full | Low-frequency variation in TP53 has large effects on head circumference and intracranial volume |
| title_fullStr | Low-frequency variation in TP53 has large effects on head circumference and intracranial volume |
| title_full_unstemmed | Low-frequency variation in TP53 has large effects on head circumference and intracranial volume |
| title_short | Low-frequency variation in TP53 has large effects on head circumference and intracranial volume |
| title_sort | low frequency variation in tp53 has large effects on head circumference and intracranial volume |
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