Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations

Xiaoxi Liu, Takafumi Shimada, Takeshi Otowa, Yu Yu Wu, Yoshiya Kawamura, Mamoru Tochigi, Yasuhide Iwata, Tadashi Umekage, Tomoko Toyota, Motoko Maekawa, Yoshimi Iwayama, Katsuaki Suzuki, Chihiro Kakiuchi, Hitoshi Kuwabara, Yukiko Kano, Hisami Nishida, Toshiro Sugiyama, Nobumasa Kato, Chia Hsiang Chen, Norio MoriKazuo Yamada, Takeo Yoshikawa, Kiyoto Kasai, Katsushi Tokunaga, Tsukasa Sasaki, Susan Shur Fen Gau

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)


Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n=500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n=1,254), were genotyped by TaqMan platform. Case-control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P=6.04 × 10-7), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD.

Original languageEnglish
Pages (from-to)340-349
Number of pages10
JournalAutism Research
Issue number3
Publication statusPublished - 2016 Mar 1
Externally publishedYes


  • Autism
  • Autism spectrum disorder
  • Common variation
  • Genetics
  • Genome-wide association study

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Genetics(clinical)


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