Dataset Information

Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders.

ABSTRACT: Imaging genetics provides an opportunity to discern associations between genetic variants and brain imaging phenotypes. Historically, the field has focused on adults and adolescents; very few imaging genetics studies have focused on brain development in infancy and early childhood (from birth to age 6 years). This is an important knowledge gap because developmental changes in the brain during the prenatal and early postnatal period are regulated by dynamic gene expression patterns that likely play an important role in establishing an individual's risk for later psychiatric illness and neurodevelopmental disabilities. In this review, we summarize findings from imaging genetics studies spanning from early infancy to early childhood, with a focus on studies examining genetic risk for neuropsychiatric disorders. We also introduce the Organization for Imaging Genomics in Infancy (ORIGINs), a working group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium, which was established to facilitate large-scale imaging genetics studies in infancy and early childhood.

SUBMITTER: Alex AM

PROVIDER: S-EPMC10136952 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders.

Alex Ann M AM Buss Claudia C Davis Elysia Poggi EP Campos Gustavo de Los GL Donald Kirsten A KA Fair Damien A DA Gaab Nadine N Gao Wei W Gilmore John H JH Girault Jessica B JB Grewen Karen K Groenewold Nynke A NA Hankin Benjamin L BL Ipser Jonathan J Kapoor Shreya S Kim Pilyoung P Lin Weili W Luo Shan S Norton Elizabeth S ES O'Connor Thomas G TG Piven Joseph J Qiu Anqi A Rasmussen Jerod M JM Skeide Michael A MA Stein Dan J DJ Styner Martin A MA Thompson Paul M PM Wakschlag Laurie L Knickmeyer Rebecca R

Biological psychiatry 20230128 10

Imaging genetics provides an opportunity to discern associations between genetic variants and brain imaging phenotypes. Historically, the field has focused on adults and adolescents; very few imaging genetics studies have focused on brain development in infancy and early childhood (from birth to age 6 years). This is an important knowledge gap because developmental changes in the brain during the prenatal and early postnatal period are regulated by dynamic gene expression patterns that likely pl ...[more]

PMID: 36932005

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Project description:The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer's disease (AD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain "insulinopathies" were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (rg = -0.315, p = 3.9 × 10-8), OCD and obesity (rg = -0.379, p = 3.4 × 10-5), and OCD and T2DM (rg = -0.172, p = 3 × 10-4). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p < 6.17 × 10-4). Stratified analyses showed negative genetic covariances between AD, ASD, OCD, ADHD, AN, bipolar disorder, schizophrenia and somatic insulinopathies through gene sets related to insulin signalling and insulin receptor recycling, and positive genetic covariances between AN and T2DM, as well as ADHD and MetS through gene sets related to insulin processing/secretion (p < 2.06 × 10-4). Overall, our findings suggest the existence of two clusters of neuropsychiatric disorders, in which the genetics of insulin-related diseases/traits may exert divergent pleiotropic effects. These results represent a starting point for a new research line on "insulinopathies" of the brain.

Dataset Information

Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders.

Publications

Genetic Influences on the Developing Young Brain and Risk for Neuropsychiatric Disorders.

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