Integrated gene analyses of de novo variants from 46,612 trios with autism and developmental disorders
Heritability of autism
DOI:
10.1073/pnas.2203491119
Publication Date:
2022-11-09T18:48:31Z
AUTHORS (174)
ABSTRACT
Most genetic studies consider autism spectrum disorder (ASD) and developmental (DD) separately despite overwhelming comorbidity shared etiology. Here, we analyzed de novo variants (DNVs) from 15,560 ASD (6,557 SPARK) 31,052 DD trios independently also combined as broader neurodevelopmental disorders (NDDs) using three models. We identify 615 NDD candidate genes (false discovery rate [FDR] < 0.05) supported by ≥1 models, including 138 reaching Bonferroni exome-wide significance (P 3.64e-7) in all The group into five functional networks associating with different brain lineages based on single-cell nuclei transcriptomic data. find no evidence for ASD-specific contrast to 18 significantly enriched DD. There are 53 that show mutational bias, enrichments missense (n = 41) or truncating 12) DNVs. 10 of male- female-bias enrichment, 4 X chromosome significant female burden (DDX3X, MECP2, WDR45, HDAC8). This large-scale integrative analysis identifies candidates subsets genes.
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