Association of Genetic Risks With Autism Spectrum Disorder and Early Neurodevelopmental Delays Among Children Without Intellectual Disability

Abstract

IMPORTANCE Autism spectrum disorder (ASD) is highly heritable, and modest contributions of common genetic variants to ASD have been reported. However, the association of genetic risks derived from common risk variants with ASD traits in children from the general population is not clear, and the association of these genetic risks with neurodevelopment in infants has not been well understood.OBJECTIVE To test whether a polygenic risk score (PRS) for ASD is associated with neurodevelopmental progress at age 18 months and ASD traits at age 6 years among children from the general population. DESIGN, SETTING, AND PARTICIPANTSIn this cohort study, 876 children in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan, underwent testing for the association of an ASD PRS with neurodevelopmental progress and ASD traits. Data collection began in December 2007 and is ongoing. Data analysis was conducted from April to December 2019. MAIN OUTCOMES AND MEASURES Summary data from the largest genome-wide association study were used to generate ASD PRSs, and significance of thresholds was calculated for each outcome. The Autism Diagnostic Observation Schedule 2 was used to measure ASD traits at age 6 years, and the Mullen Scales of Early Learning was used to measure neurodevelopmental progress at age 18 months.

Heterogeneity and Polygenicity in Psychiatric Disorders: A Genome-Wide Perspective

“…These sex differences have recently been implicated in investigation strategies of empathizing-systemizing and automatizing-systemizing theories of ASD heterogeneity. 97,98,[104][105][106] The polygenic risk for ASD has been associated with cognitive ability, 107 various changes in DNA methylation at birth, 108 and gray matter volume in healthy and psychiatric patients. 109 Studies of the relationship between genetic risk for ASD and other human health and disease phenotypes have revealed interesting findings.…”

“…First, ASD genetic risk indeed predicts ASD severity; however, ASD PRS do not cleanly stratify individuals into more clinically severe ASD symptom criteria. 107,110 This observation suggests that though phenotypic ASD subtypes exist, they may not appropriately stratify ASD for genetic studies. 96 Second, the genetic risk for ASD in ASD unaffected individuals (i.e.…”

Mucopolysacaridosis Type Iiib Misdiagnosed as an Autistic Spectrum Disorder: A Case Report and Literature Review

“… 7 Genetic factors play an important role in the development of this condition, seen that the heritability rate of the disorder is approximately 80%. 9 The American Academy of Pediatrics guides targeted research in case of suspicion of specific genetic disease and, in other situations, analysis of chromosomal microarray, research of fragile X in families with an inheritance pattern linked to sex and suggests considering the sequencing of the gene MECP2 in girls. In cases in which the investigation is inconclusive, complete exome sequencing can be performed.…”

Elevated risk of attention deficit hyperactivity disorder (ADHD) in Japanese children with higher genetic susceptibility to ADHD with a birth weight under 2000 g

“…PRS represents the approximate genetic liability for a disease or disorder using the number of risk alleles from a set of single-nucleotide polymorphisms (SNPs) [46]. The detailed estimation procedure of the PRS and quality controls of SNPs in the HBC study were described in our previous study [47]. Trained clinicians collected buccal swabs (DNA samples) from children during the follow-up surveys conducted either at age 32 months, 40 months, 4.5 years, or 6 years.…”