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Recent genetic and functional insights in autism spectrum disorder

Nakanishi, Moea; Anderson, Matthew P.b,c,d; Takumi, Torua,e

doi: 10.1097/WCO.0000000000000718

Purpose of review Recent advances in genetic technologies allowed researchers to identify large numbers of candidate risk genes associated with autism spectrum disorder (ASD). Both strongly penetrant rare variants and the accumulation of common variants with much weaker penetrance contribute to the cause of ASD. To identify the highly confident candidate genes, software and resources have been applied, and functional evaluation of the variants has provided further insights for ASD pathophysiology. These studies ultimately identify the molecular and circuit alteration underlying the behavioral abnormalities in ASD. In this review, we introduce the recent genetic and genomic findings and functional approaches for ASD variants providing a deeper understanding of the etiology of ASD.

Recent findings Integrated meta-analysis that recruited a larger number of ASD cases has helped to prioritize ASD candidate genes or genetic loci into highly confidence candidate genes for further investigation. Not only coding but also noncoding variants have been recently implicated to confer the risk of ASD. Functional approaches of genes or variants revealed the disruption of specific molecular pathways. Further studies combining ASD genetics and genomics with recent techniques in engineered mouse models show molecular and circuit mechanisms underlying the behavioral deficits in ASD.

Summary Advances in ASD genetics and the following functional studies provide significant insights into ASD pathophysiology at molecular and circuit levels.

aRIKEN Brain Science Institute, Wako, Saitama, Japan

bDepartments of Neurology and Pathology, Beth Israel Deaconess Medical Center

cBoston Children's Hospital Intellectual and Developmental Disabilities Research Center

dProgram in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA

eDepartment of Physiology and Cell Biology, Kobe University School of Medicine, Kobe, Japan

Correspondence to Toru Takumi, MD, PhD, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Tel: +81 48 467 5906; fax:+81 48 467 6079; e-mail:

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