Developmental milestones in early childhood and genetic liability to neurodevelopmental disorders

Abstract Background Timing of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to genetic risk for neurodevelopmental disorders in the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Methods We use data from a genotyped sub-set (N = 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences. Results We found that ADHD PGS were associated with earlier walking age (β = −0.033, padj < 0.001) in both males and females. Additionally, autism PGS were associated with later walking (β = 0.039, padj = 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment. Conclusions Genetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.

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Developmental milestones in early childhood and genetic liability to neurodevelopmental disorders

10.31234/osf.io/x8wst ◽

2020 ◽

Author(s):

Laurie John Hannigan ◽

Ragna Bugge Askeland ◽

Helga Ask ◽

Martin Tesli ◽

Elizabeth Corfield ◽

...

Keyword(s):

Language Development ◽

Motor Development ◽

Neurodevelopmental Disorders ◽

Autism Spectrum ◽

Probit Regression ◽

Developmental Milestones ◽

Genetic Liability ◽

Polygenic Scores ◽

Walking Age ◽

Children First

BackgroundEarly developmental milestones, such as the age at first walking or talking, are associated with later diagnoses of neurodevelopmental disorders, but the relationship to genetic risk for neurodevelopmental disorders are unknown. Here, we investigate associations between genetic liability to autism spectrum disorder (autism), attention deficit hyperactivity disorder (ADHD), and schizophrenia and attainment of early-life language and motor development milestones.MethodsWe use data from a genotyped sub-set (N = 15 205) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). In this sample, we calculate polygenic scores for autism; ADHD and schizophrenia and predict maternal reports of children’s age at first walking and talking, motor delays at 18 months, language delays at 3 years, and a generalized measure of concerns about development. We use linear and probit regression models in a multi-group framework to test for sex differences.ResultsADHD polygenic scores predicted earlier walking age in both males and females (β=-0.037, pFDR=0.001), and earlier first use of sentences (β=-0.087, pFDR=0.032) but delayed language development at 3 years in females only (β=0.194, pFDR=0.001). Additionally, we found evidence that autism polygenic scores were associated with later walking (β=0.027, pFDR=0.024) and motor delays at 18 months (β = 0.065, pFDR=0.028). Schizophrenia polygenic scores were associated with a measure of general concerns about development at 3 years in females only (β=0.132, pFDR=0.024).ConclusionsGenetic liabilities for neurodevelopmental disorders show some specific associations with measures of early motor and language development in the general population, including the age at which children first walk and talk. Associations are generally small and occasionally in unexpected directions. Sex differences are evident in some instances, but clear patterns across different polygenic scores and outcomes are hard to discern. These findings suggest that genetic susceptibility for neurodevelopmental disorders is manifested in the timing of developmental milestones in infancy.

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Is the Age of Developmental Milestones a Predictor for Future Development in Down Syndrome?

Brain Sciences ◽

10.3390/brainsci11050655 ◽

2021 ◽

Vol 11 (5) ◽

pp. 655

Author(s):

Chiara Locatelli ◽

Sara Onnivello ◽

Francesca Antonaros ◽

Agnese Feliciello ◽

Sonia Filoni ◽

...

Keyword(s):

Down Syndrome ◽

Motor Development ◽

Adaptive Functioning ◽

Neural Substrates ◽

Adaptive Skills ◽

Typically Developing ◽

Older Children ◽

Developmental Milestones ◽

Developmental Milestone ◽

The Relationship

Down Syndrome (DS) is the most common genetic alteration responsible for intellectual disability, which refers to deficits in both intellectual and adaptive functioning. According to this, individuals with Down Syndrome (DS) reach developmental milestones (e.g., sitting, walking, and babbling) in the same order as their typically developing peers, but later in life. Since developmental milestones are the first blocks on which development builds, the aims of the current study are to: (i) expand the knowledge of developmental milestone acquisition; and (ii) explore the relationship between developmental milestone acquisition and later development. For this purpose 105 children/adolescents with DS were involved in this study, divided in two groups, Preschoolers (n = 39) and School-age participants (n = 66). Information on the age of acquisition of Sitting, Walking, Babbling, and Sphincter Control was collected, together with cognitive, motor, and adaptive functioning. Sitting predicted later motor development, but, with age, it became less important in predicting motor development in everyday life. Babbling predicted later language development in older children. Finally, Sphincter Control emerged as the strongest predictor of motor, cognitive, language, and adaptive skills, with its role being more evident with increasing age. Our data suggest that the age of reaching the milestones considered in the study has an influence on successive development, a role that can be due to common neural substrates, the environment, and the developmental cascade effect.

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Early-life lead exposure and neurodevelopmental disorders

Current Opinion in Toxicology ◽

10.1016/j.cotox.2021.03.007 ◽

2021 ◽

Author(s):

D. Albores-Garcia ◽

J.L. McGlothan ◽

T.R. Guilarte

Keyword(s):

Lead Exposure ◽

Neurodevelopmental Disorders ◽

Early Life

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Diet-induced dysbiosis of the maternal gut microbiome in early life programming of neurodevelopmental disorders

Neuroscience Research ◽

10.1016/j.neures.2021.05.003 ◽

2021 ◽

Author(s):

Claudia M. Di Gesù ◽

Lisa M. Matz ◽

Shelly A. Buffington

Keyword(s):

Gut Microbiome ◽

Neurodevelopmental Disorders ◽

Early Life ◽

Early Life Programming

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Growth in ataxia telangiectasia

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01716-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Valerie A. I. Natale ◽

Tim J. Cole ◽

Cynthia Rothblum-Oviatt ◽

Jennifer Wright ◽

Thomas O. Crawford ◽

...

Keyword(s):

General Population ◽

Ataxia Telangiectasia ◽

Early Life ◽

Chronic Infection ◽

Severe Form ◽

Growth Patterns ◽

Childhood And Adolescence ◽

Poor Growth ◽

Growth References ◽

Weight Faltering

Abstract Background Ataxia telangiectasia (A-T) is a DNA repair disorder that affects multiple body systems. Neurological problems and immunodeficiency are two important features of this disease. At this time, two main severity groups are defined in A-T: classic (the more severe form) and mild. Poor growth is a common problem in classic A-T. An objective of this study was to develop growth references for classic A-T. Another objective was to compare growth patterns in classic A-T and mild A-T with each other and with the general population, using the CDC growth references. A final objective was to examine the effects of chronic infection on height. Results We found that classic A-T patients were smaller overall, and suffered from height and weight faltering that continued throughout childhood and adolescence. When compared to the CDC growth references, the median heights and weights for both male and female patients eventually fell to or below the 3rd centile on the CDC charts. Height faltering was more pronounced in females. Birthweight was lower in the classic A-T group compared to mild A-T and the general population, whereas birth length was not. Finally, we investigated height and BMI faltering in relation to number of infections and found no association. Conclusions Classic A-T appears to affect growth in utero. Although children appear to grow well in very early life, faltering begins early, and is unrelenting.

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Angelman Syndrome: An Autism Spectrum Disorder

Journal of Student Research ◽

10.47611/jsr.v6i2.399 ◽

2018 ◽

Vol 6 (2) ◽

pp. 56-60

Author(s):

Andrew J. Kennedy ◽

Jeffrey O. Henderson

Keyword(s):

Angelman Syndrome ◽

Motor Development ◽

Neurodevelopmental Disorders ◽

Muscle Tension ◽

Autism Spectrum ◽

Speech Impairment ◽

Social Lives ◽

Genetic Abnormalities ◽

Ube3a Gene ◽

Genetic Mechanisms

Neurodevelopmental disorders limit the mental, physical, and social lives of affected individuals and their families. These disorders are often related to genetic abnormalities having a distinct chromosomal location. The abnormalities can cause incorrect proteins to be formed or biochemical pathways to be blocked, predominately affecting brain development, but also having pleiotropic effects. Research into defining and correcting these genetic abnormalities is important to help distinguish between unique neurodevelopmental disorders so that proper clinical interventions are available for affected individuals. In the following review, Angelman syndrome, which results from UBE3A gene function being lost at maternal chromosome 15q11.2-q13, will be discussed. Angelman patients suffer from the defining characteristics of speech impairment, uncontrolled laughing and smiling, motor development issues, muscle tension, and possible ataxia. The genetic mechanisms of the disorder as well as possible therapies will be discussed, with future areas of research into genetic therapies to treat Angelman syndrome also put forth. Research into Angelman syndrome can provide an avenue for a clearer understanding of other neurodevelopmental disorders.

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Discrimination and anxiety: Using multiple polygenic scores to control for genetic liability

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2017224118 ◽

2020 ◽

Vol 118 (1) ◽

pp. e2017224118

Author(s):

Adolfo G. Cuevas ◽

Frank D. Mann ◽

David R. Williams ◽

Robert F. Krueger

Keyword(s):

Negative Affect ◽

Principal Components ◽

The United States ◽

European Ancestry ◽

Prevention Measures ◽

Latent Factor ◽

Genetic Liability ◽

Polygenic Scores ◽

Anxiety Depression ◽

The Impact

An established body of research indicates that discrimination is associated with increased symptoms of anxiety and negative affect. However, the association cannot be interpreted unambiguously as an exposure effect because a common set of genetic factors can simultaneously contribute to increased liability for symptoms of anxiety, negative affect, and the perception of discrimination. The present study elucidates the association between discrimination and anxiety/negative affect by implementing strict genetic controls in a large sample of adults. We used data from the biomarker project of the Study of Midlife Development in the United States (MIDUS), a national probability sample of noninstitutionalized, English-speaking respondents aged 25 to 74 y. Participants who consented to provide genetic data were biologically unrelated and of European ancestry as determined by genotype principal components analysis (n = 1,146). A single structural regression model was fit to the data with three measures of discrimination specified to load onto a latent factor and six measures of anxiety and negative affect specified to load onto a second latent factor. After accounting for potential genetic confounds—polygenic scores for anxiety, depression, and neuroticism and the first five genetic principal components—greater discrimination was associated with greater anxiety/negative affect (β = 0.53, SE = 0.04, P < 0.001). Findings suggest that measures of perceived discrimination should be considered environmental risk factors for anxiety/negative affect rather than indices of genetic liability for anxiety, depression, or neuroticism. Clinical interventions and prevention measures should focus on ways to mitigate the impact of discrimination to improve mental health at the population level.

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