|Title:||Genome-wide association study for autism spectrum disorder in taiwanese han population||Authors:||Kuo P.-H.
|Issue Date:||2015||Publisher:||Public Library of Science||Journal Volume:||10||Journal Issue:||9||Start page/Pages:||e0138695||Source:||PLoS ONE||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. ? 2015 Kuo et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|ISSN:||1932-6203||DOI:||10.1371/journal.pone.0138695||metadata.dc.subject.other:||G protein coupled receptor; genomic DNA; basic helix loop helix leucine zipper transcription factor; DNA binding protein; GLIS1 protein, human; glutamate carboxypeptidase II; MNT protein, human; NAALADL2 protein, human; protein tyrosine kinase; repressor protein; STYK1 protein, human; transcription factor; Article; autism; child; controlled study; female; gene; gene mapping; genetic analysis; genetic association; genetic marker; genetic susceptibility; genetic variability; genotype; GLIPR1 gene; GLIS1 gene; Han Chinese; haplotype; human; KRR1 gene; major clinical study; male; MNT gene; molecular pathology; NAALADL2 gene; olfactory receptor; OR2M3 gene; OR2M4 gene; OR2T5 gene; signal transduction; single nucleotide polymorphism; STYK1 gene; Taiwanese; adolescent; Asian continental ancestry group; autism; case control study; chromosomal mapping; ethnology; genetics; genome-wide association study; pathology; Taiwan; young adult; Adolescent; Asian Continental Ancestry Group; Autism Spectrum Disorder; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Case-Control Studies; Child; Chromosome Mapping; DNA-Binding Proteins; Female; Genome-Wide Association Study; Genotype; Glutamate Carboxypeptidase II; Haplotypes; Humans; Male; Polymorphism, Single Nucleotide; Receptor Protein-Tyrosine Kinases; Repressor Proteins; Taiwan; Transcription Factors; Young Adult
|Appears in Collections:||醫學系|
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