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• W3005168281 abstract "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.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.In 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.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.Of 876 participants (mean [SD] gestational age at birth, 38.9 [1.6] weeks; 438 [50.0%] boys; 868 [99.1%] Japanese), 734 were analyzed. The ASD PRS was associated with ASD traits (R2 = 0.024; β, 0.71; SE, 0.24; P = .03). The association of ASD PRS with infant neurodevelopment was most pronounced in gross motor (R2 = 0.015; β, -1.25; SE, 0.39; P = .01) and receptive language (R2 = 0.014; β, -1.19; SE, 0.39; P = .02) scores on the Mullen Scales of Early Learning. Gene set enrichment analyses found that several pathways, such as cell maturation (R2 = 0.057; β, -5.28; SE, 1.40; P < .001) and adenylyl cyclase activity and cyclic adenosine monophosphate concentration (R2 = 0.064; β, -5.30; SE 1.30; P < .001), were associated with ASD traits. Gene sets associated with inflammation were commonly enriched with ASD traits and gross motor skills (eg, chemokine motif ligand 2 production: R2 = 0.051; β, -6.04; SE, 1.75; P = .001; regulation of monocyte differentiation: R2 = 0.052; β, -6.63; SE, 1.90; P = .001; and B-cell differentiation: R2 = 0.051; β, 7.37; SE, 2.15; P = .001); glutamatergic signaling-associated gene sets were commonly enriched with ASD traits and receptive language skills (eg, regulation of glutamate secretion: R2 = 0.052; β, -5.82; SE, 1.68; P = .001; ionotropic glutamate receptor signaling pathway: R2 = 0.047; β, 3.54; SE, 1.09; P = .001; and negative regulation of glutamate secretion: R2 = 0.045; β, -5.38; SE, 1.74; P = .002).In this study, the ASD PRS was associated with ASD traits among children from the general population. Genetic risks for ASD might be associated with delays in some neurodevelopmental domains, such as gross motor and receptive language skills." @default.
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• W3005168281 date "2020-02-07" @default.
• W3005168281 modified "2023-10-12" @default.
• W3005168281 title "Association of Genetic Risks With Autism Spectrum Disorder and Early Neurodevelopmental Delays Among Children Without Intellectual Disability" @default.
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• W3005168281 doi "https://doi.org/10.1001/jamanetworkopen.2019.21644" @default.
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