title: Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population.
abstract: BACKGROUND
  Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic components. Several recent genome-wide association (GWA) studies in Caucasian samples have reported a number of gene regions and loci correlated with the risk of ASD--albeit with very little consensus across studies.
  
  
  METHODS
  A two-stage GWA study was employed to identify common genetic variants for ASD in the Taiwanese Han population. The discovery stage included 315 patients with ASD and 1,115 healthy controls, using the Affymetrix SNP array 6.0 platform for genotyping. Several gene regions were then selected for fine-mapping and top markers were examined in extended samples. Single marker, haplotype, gene-based, and pathway analyses were conducted for associations.
  
  
  RESULTS
  Seven SNPs had p-values ranging from 3.4~9.9*10-6, but none reached the genome-wide significant level. Five of them were mapped to three known genes (OR2M4, STYK1, and MNT) with significant empirical gene-based p-values in OR2M4 (p = 3.4*10(-5)) and MNT (p = 0.0008). Results of the fine-mapping study showed single-marker associations in the GLIS1 (rs12082358 and rs12080993) and NAALADL2 (rs3914502 and rs2222447) genes, and gene-based associations for the OR2M3-OR2T5 (olfactory receptor genes, p = 0.02), and GLIPR1/KRR1 gene regions (p = 0.015). Pathway analyses revealed important pathways for ASD, such as olfactory and G protein-coupled receptors signaling pathways.
  
  
  CONCLUSIONS
  We reported Taiwanese Han specific susceptibility genes and variants for ASD. However, further replication in other Asian populations is warranted to validate our findings. Investigation in the biological functions of our reported genetic variants might also allow for better understanding on the underlying pathogenesis of autism.
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Research Center for Genes, Environment and Human Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Po-Hsiu
authors.initials: PH
authors.lastname: Kuo
authors.affiliation: Department of Nursing, Cardinal Tien Junior College of Healthcare & Management, I-Lan, Taiwan.
authors.forename: Li-Chung
authors.initials: LC
authors.lastname: Chuang
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Hsin
authors.initials: MH
authors.lastname: Su
authors.affiliation: Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan; Department and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Yen
authors.affiliation: Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan.
authors.forename: Yu-Yu
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Department of Child and Adolescent Psychiatry, Taoyaun Psychiatric Center, Ministry of Health and Welfare, Taoyuan, Taiwan.
authors.forename: Shih-Kai
authors.initials: SK
authors.lastname: Liu
authors.affiliation: Department of Child Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Miao-Chun
authors.initials: MC
authors.lastname: Chou
authors.affiliation: Department of Child Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Wen-Jiun
authors.initials: WJ
authors.lastname: Chou
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Yen-Nan
authors.initials: YN
authors.lastname: Chiu
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Wen-Che
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Susan Shur-Fen
authors.initials: SS
authors.lastname: Gau
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D000067877:Autism Spectrum Disorder / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D043425:Glutamate Carboxypeptidase II / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D013624:Taiwan / Q000208:ethnology; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C508055:GLIS1 protein, human; C106465:MNT protein, human; C000597036:NAALADL2 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases; C482299:STYK1 protein, human; D043425:Glutamate Carboxypeptidase II