Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations
Journal
Autism Research
Journal Volume
9
Journal Issue
3
Pages
340-349
Date Issued
2016
Author(s)
Liu X.
Shimada T.
Otowa T.
Wu Y.-Y.
Kawamura Y.
Tochigi M.
Iwata Y.
Umekage T.
Toyota T.
Maekawa M.
Iwayama Y.
Suzuki K.
Kakiuchi C.
Kuwabara H.
Kano Y.
Nishida H.
Sugiyama T.
Kato N.
Chen C.-H.
Mori N.
Yamada K.
Yoshikawa T.
Kasai K.
Tokunaga K.
Sasaki T.
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.
SDGs
Type
journal article