Dataset Information

Environmental Influences on Infant Cortical Thickness and Surface Area.

ABSTRACT: 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.

SUBMITTER: Jha SC

PROVIDER: S-EPMC6373689 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Environmental Influences on Infant Cortical Thickness and Surface Area.

Jha Shaili C SC Xia Kai K Ahn Mihye M Girault Jessica B JB Li Gang G Wang Li L Shen Dinggang D Zou Fei F Zhu Hongtu H Styner Martin M Gilmore John H JH Knickmeyer Rebecca C RC

Cerebral cortex (New York, N.Y. : 1991) 20190301 3

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 ...[more]

PMID: 29420697

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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.

Dataset Information

Environmental Influences on Infant Cortical Thickness and Surface Area.

Publications

Environmental Influences on Infant Cortical Thickness and Surface Area.

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