title: Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations.
abstract: 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.
authors: Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Xiaoxi
authors: X
authors: Liu
authors: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Takafumi
authors: T
authors: Shimada
authors: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Otowa
authors: Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan.
authors: Yu-Yu
authors: YY
authors: Wu
authors: Department of Psychiatry, Sakae Seijinkai Hospital, Kanagawa, Japan.
authors: Yoshiya
authors: Y
authors: Kawamura
authors: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Mamoru
authors: M
authors: Tochigi
authors: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors: Yasuhide
authors: Y
authors: Iwata
authors: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Tadashi
authors: T
authors: Umekage
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors: Tomoko
authors: T
authors: Toyota
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors: Motoko
authors: M
authors: Maekawa
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors: Yoshimi
authors: Y
authors: Iwayama
authors: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors: Katsuaki
authors: K
authors: Suzuki
authors: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Chihiro
authors: C
authors: Kakiuchi
authors: Department of Child Psychiatry, University of Tokyo Hospital, Tokyo, Japan.
authors: Hitoshi
authors: H
authors: Kuwabara
authors: Department of Child Psychiatry, University of Tokyo Hospital, Tokyo, Japan.
authors: Yukiko
authors: Y
authors: Kano
authors: Asunaro Hospital for Child and Adolescent Psychiatry, Tsu, Japan.
authors: Hisami
authors: H
authors: Nishida
authors: Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors: Toshiro
authors: T
authors: Sugiyama
authors: Department of Psychiatry, Graduate School of Medicine, University of Showa, Tokyo, Japan.
authors: Nobumasa
authors: N
authors: Kato
authors: Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan.|Department and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors: Chia-Hsiang
authors: CH
authors: Chen
authors: Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors: Norio
authors: N
authors: Mori
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors: Kazuo
authors: K
authors: Yamada
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors: Takeo
authors: T
authors: Yoshikawa
authors: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Kiyoto
authors: K
authors: Kasai
authors: Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Katsushi
authors: K
authors: Tokunaga
authors: Department of Physical and Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan.
authors: Tsukasa
authors: T
authors: Sasaki
authors: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors: Susan Shur-Fen
authors: SS
authors: Gau
mesh_terms: D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data*; D006801:Humans; D007564:Japan; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013624:Taiwan
keywords: autism; autism spectrum disorder; common variation; genetics; genome-wide association study