Genetic Influences on Longitudinal Trajectories of Cortical Thickness and Surface Area during the First 2 Years of Life.
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ABSTRACT:
SUBMITTER: Xia K
PROVIDER: S-EPMC8897991 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.
| S-EPMC2758684 | biostudies-literature
Project description:Cortical thickness (CT) and surface area (SA) vary widely between individuals and are associated with intellectual ability and risk for various psychiatric and neurodevelopmental conditions. Factors influencing this variability remain poorly understood, but the radial unit hypothesis, as well as the more recent supragranular cortex expansion hypothesis, suggests that prenatal and perinatal influences may be particularly important. In this report, we examine the impact of 17 major demographic and obstetric history variables on interindividual variation in CT and SA in a unique sample of 805 neonates who received MRI scans of the brain around 2 weeks of age. Birth weight, postnatal age at MRI, gestational age at birth, and sex emerged as important predictors of SA. Postnatal age at MRI, paternal education, and maternal ethnicity emerged as important predictors of CT. These findings suggest that individual variation in infant CT and SA is explained by different sets of environmental factors with neonatal SA more strongly influenced by sex and obstetric history and CT more strongly influenced by socioeconomic and ethnic disparities. Findings raise the possibility that interventions aimed at reducing disparities and improving obstetric outcomes may alter prenatal/perinatal cortical development.
| S-EPMC6373689 | biostudies-literature
Project description:Genetic and environmental influences on cortical thickness (CT) and surface area (SA) are thought to vary in a complex and dynamic way across the lifespan. It has been established that CT and SA are genetically distinct in older children, adolescents, and adults, and that heritability varies across cortical regions. Very little, however, is known about how genetic and environmental factors influence infant CT and SA. Using structural MRI, we performed the first assessment of genetic and environmental influences on normal variation of SA and CT in 360 twin neonates. We observed strong and significant additive genetic influences on total SA (a2 = 0.78) and small and nonsignificant genetic influences on average CT (a2 = 0.29). Moreover, we found significant genetic overlap (genetic correlation = 0.65) between these global cortical measures. Regionally, there were minimal genetic influences across the cortex for both CT and SA measures and no distinct patterns of genetic regionalization. Overall, outcomes from this study suggest a dynamic relationship between CT and SA during the neonatal period and provide novel insights into how genetic influences shape cortical structure during early development.
| S-EPMC6218288 | biostudies-literature
Project description:Sex hormones have been shown to contribute to the organization and function of the brain during puberty and adolescence. Moreover, it has been suggested that distinct hormone changes in girls versus boys may contribute to the emergence of sex differences in internalizing and externalizing behavior during adolescence. In the current longitudinal study, the influence of within-subject changes in puberty (physical and hormonal) on cortical thickness and surface area was examined across a 2-year span, while controlling for age. Greater increases in Tanner Stage predicted less superior frontal thinning and decreases in precuneus surface area in both sexes. Significant Tanner Stage and sex interactions were also seen, with less right superior temporal thinning in girls but not boys, as well as greater decreases in the right bank of the superior temporal sulcus surface area in boys compared to girls. In addition, within-subject changes in testosterone over the 2-year follow-up period were found to relate to decreases in middle superior frontal surface area in boys, but increases in surface area in girls. Lastly, larger increases in estradiol in girls predicted greater middle temporal lobe thinning. These results show that within-subject physical and hormonal markers of puberty relate to region and sex-specific changes in cortical development across adolescence.
| S-EPMC4368209 | biostudies-literature
Project description:What we know about cortical development during adolescence largely stems from analyses of cross-sectional or cohort-sequential samples, with few studies investigating brain development using a longitudinal design. Further, cortical volume is a product of two evolutionarily and genetically distinct features of the cortex - thickness and surface area, and few studies have investigated development of these three characteristics within the same sample. The current study examined maturation of cortical thickness, surface area and volume during adolescence, as well as sex differences in development, using a mixed longitudinal design. 192 MRI scans were obtained from 90 healthy (i.e., free from lifetime psychopathology) adolescents (11-20 years) at three time points (with different MRI scanners used at time 1 compared to 2 and 3). Developmental trajectories were estimated using linear mixed models. Non-linear increases were present across most of the cortex for surface area. In comparison, thickness and volume were both characterised by a combination of non-linear decreasing and increasing trajectories. While sex differences in volume and surface area were observed across time, no differences in thickness were identified. Furthermore, few regions exhibited sex differences in the cortical development. Our findings clearly illustrate that volume is a product of surface area and thickness, with each exhibiting differential patterns of development during adolescence, particularly in regions known to contribute to the development of social-cognition and behavioral regulation. These findings suggest that thickness and surface area may be driven by different underlying mechanisms, with each measure potentially providing independent information about brain development. Hum Brain Mapp 37:2027-2038, 2016. © 2016 Wiley Periodicals, Inc.
| S-EPMC6867680 | biostudies-literature
Project description:Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention. Longitudinal study including 15 samples
2016-06-15 | E-GEOD-83334 | biostudies-arrayexpress
Project description:Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention.
2016-06-15 | GSE83334 | GEO
Project description:This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1-3 per subject, total scans n=753) from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.?s article "Trajectories of cortical thickness maturation in normal brain development - the importance of quality control procedures" (Ducharme et al., 2015) [1].
| S-EPMC4669480 | biostudies-literature
Project description:ImportanceSchizophrenia is a complex heritable disorder associated with many genetic variants, each with a small effect. While cortical differences between patients with schizophrenia and healthy controls are consistently reported, the underlying molecular mechanisms remain elusive.ObjectiveTo investigate the extent of shared genetic architecture between schizophrenia and brain cortical surface area (SA) and thickness (TH) and to identify shared genomic loci.Design, setting, and participantsIndependent genome-wide association study data on schizophrenia (Psychiatric Genomics Consortium and CLOZUK: n = 105 318) and SA and TH (UK Biobank: n = 33 735) were obtained. The extent of polygenic overlap was investigated using MiXeR. The specific shared genomic loci were identified by conditional/conjunctional false discovery rate analysis and were further examined in 3 independent cohorts. Data were collected from December 2019 to February 2021, and data analysis was performed from May 2020 to February 2021.Main outcomes and measuresThe primary outcomes were estimated fractions of polygenic overlap between schizophrenia, total SA, and average TH and a list of functionally characterized shared genomic loci.ResultsBased on genome-wide association study data from 139 053 participants, MiXeR estimated schizophrenia to be more polygenic (9703 single-nucleotide variants [SNVs]) than total SA (2101 SNVs) and average TH (1363 SNVs). Most SNVs associated with total SA (1966 of 2101 [93.6%]) and average TH (1322 of 1363 [97.0%]) may be associated with the development of schizophrenia. Subsequent conjunctional false discovery rate analysis identified 44 and 23 schizophrenia risk loci shared with total SA and average TH, respectively. The SNV associations of shared loci between schizophrenia and total SA revealed en masse concordant association between the discovery and independent cohorts. After removing high linkage disequilibrium regions, such as the major histocompatibility complex region, the shared loci were enriched in immunologic signature gene sets. Polygenic overlap and shared loci between schizophrenia and schizophrenia-associated regions of interest for SA (superior frontal and middle temporal gyri) and for TH (superior temporal, inferior temporal, and superior frontal gyri) were also identified.Conclusions and relevanceThis study demonstrated shared genetic loci between cortical morphometry and schizophrenia, among which a subset are associated with immunity. These findings provide an insight into the complex genetic architecture and associated with schizophrenia.
| S-EPMC8223140 | biostudies-literature
Project description:ObjectivesSo far, few studies have investigated cortical thickness (CT) and surface area (SA) measures in bipolar disorder type I (BDI) in comparison to a high genetic risk group such as first-degree relatives (FR). This study aimed to examine CT and SA differences between BDI, FR and healthy controls (HC).Methods3D T1 magnetic resonance images were acquired from 27 euthymic BDI patients, 24 unaffected FR and 29 HC. CT and SA measures were obtained with FreeSurfer version 5.3.0. Generalized estimating equations were used to compare CT and SA between groups. Group comparisons were repeated with restricting the FR group to 17 siblings (FR-SB) only.Results\Mean age in years was 36.3 ± 9.5 for BDI, 32.1 ± 10.9 for FR, 34.7 ± 9.8 for FR-SB and 33.1 ± 9.0 for HC group respectively. BDI patients revealed larger SA of left pars triangularis (LPT) compared to HC (p = .001). In addition, increased SA in superior temporal cortex (STC) in FR-SB group compared to HC was identified (p = .0001).ConclusionsOur result of increased SA in LPT of BDI could be a disease marker and increased SA in STC of FR-SB could be a marker related with resilience to illness.
| S-EPMC6370861 | biostudies-literature