Dataset Information

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

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.

SUBMITTER: Haworth S

PROVIDER: S-EPMC6341110 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Haworth Simon S Shapland Chin Yang CY Hayward Caroline C Prins Bram P BP Felix Janine F JF Medina-Gomez Carolina C Rivadeneira Fernando F Wang Carol C Ahluwalia Tarunveer S TS Vrijheid Martine M Guxens Mònica M Sunyer Jordi J Tachmazidou Ioanna I Walter Klaudia K Iotchkova Valentina V Jackson Andrew A Cleal Louise L Huffmann Jennifer J Min Josine L JL Sass Lærke L Timmers Paul R H J PRHJ Davey Smith George G Fisher Simon E SE Wilson James F JF Cole Tim J TJ Fernandez-Orth Dietmar D Bønnelykke Klaus K Bisgaard Hans H Pennell Craig E CE Jaddoe Vincent W V VWV Dedoussis George G Timpson Nicholas N Zeggini Eleftheria E Vitart Veronique V St Pourcain Beate B

Nature communications 20190121 1

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 determin ...[more]

PMID: 30664637

Similar Datasets

Project description:BackgroundResting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study brain functional alteration, but there have been no reports of research regarding the application of rs-fMRI in intracranial tuberculosis. The purpose of this prospective, cross-sectional study was to investigate spontaneous neural activity at different frequency bands in patients with intracranial tuberculosis using rs-fMRI with amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) methods.MethodsThe rs-fMRI data of 31 patients with intracranial tuberculosis and 30 gender-, age-, and education-matched healthy controls (HCs) were included. The ALFF and fALFF values in the conventional frequency band (0.01-0.08 Hz) and 2 sub-frequency bands (slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz) were calculated and compared between the groups. The resultant T-maps were corrected using the Gaussian random field (GRF) theory (voxel P<0.01, cluster P<0.05). Correlations between the ALFF and fALFF values and neurocognitive scores were assessed.ResultsCompared with the HCs, patients with intracranial tuberculosis showed decreased ALFF in the right paracentral lobule (T=-4.69) in the conventional frequency band, in the right supplementary motor area (T=-4.85) in the slow-4 band, and in the left supplementary motor area (T=-3.76) in the slow-5 band. Compared to the slow-5 band, the voxels with decreased ALFF were spatially more extensive in the slow-4 band. Compared with HCs, patients with intracranial tuberculosis showed decreased fALFF in the opercular parts of the right inferior frontal gyrus (T=-4.50) and the left inferior parietal lobe (T=-4.86) and increased fALFF in the left inferior cerebellum (T=5.84) in the conventional frequency band. In the slow-4 band, fALFF decreased in the opercular parts of the right inferior frontal gyrus (T=-5.29) and right precuneus (T=-4.34). In the slow-5 band, fALFF decreased in the left middle occipital gyrus (T=-4.65) and right middle frontal gyrus (T=-5.05).ConclusionsPatients with intracranial tuberculosis showed abnormal intrinsic brain activity at different frequency bands, and ALFF abnormalities in different brain regions could be better detected in the slow-4 band. This preliminary study might provide new insights into understanding the pathophysiological mechanism in intracranial tuberculosis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets