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Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population
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 acro...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580585/ https://www.ncbi.nlm.nih.gov/pubmed/26398136 http://dx.doi.org/10.1371/journal.pone.0138695 |
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author | Kuo, Po-Hsiu Chuang, Li-Chung Su, Mei-Hsin Chen, Chia-Hsiang Chen, Chien-Hsiun Wu, Jer-Yuarn Yen, Chung-Jen Wu, Yu-Yu Liu, Shih-Kai Chou, Miao-Chun Chou, Wen-Jiun Chiu, Yen-Nan Tsai, Wen-Che Gau, Susan Shur-Fen |
author_facet | Kuo, Po-Hsiu Chuang, Li-Chung Su, Mei-Hsin Chen, Chia-Hsiang Chen, Chien-Hsiun Wu, Jer-Yuarn Yen, Chung-Jen Wu, Yu-Yu Liu, Shih-Kai Chou, Miao-Chun Chou, Wen-Jiun Chiu, Yen-Nan Tsai, Wen-Che Gau, Susan Shur-Fen |
author_sort | Kuo, Po-Hsiu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4580585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45805852015-10-01 Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population Kuo, Po-Hsiu Chuang, Li-Chung Su, Mei-Hsin Chen, Chia-Hsiang Chen, Chien-Hsiun Wu, Jer-Yuarn Yen, Chung-Jen Wu, Yu-Yu Liu, Shih-Kai Chou, Miao-Chun Chou, Wen-Jiun Chiu, Yen-Nan Tsai, Wen-Che Gau, Susan Shur-Fen PLoS One Research Article 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. Public Library of Science 2015-09-23 /pmc/articles/PMC4580585/ /pubmed/26398136 http://dx.doi.org/10.1371/journal.pone.0138695 Text en © 2015 Kuo et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Kuo, Po-Hsiu Chuang, Li-Chung Su, Mei-Hsin Chen, Chia-Hsiang Chen, Chien-Hsiun Wu, Jer-Yuarn Yen, Chung-Jen Wu, Yu-Yu Liu, Shih-Kai Chou, Miao-Chun Chou, Wen-Jiun Chiu, Yen-Nan Tsai, Wen-Che Gau, Susan Shur-Fen Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population |
title | Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population |
title_full | Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population |
title_fullStr | Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population |
title_full_unstemmed | Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population |
title_short | Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population |
title_sort | genome-wide association study for autism spectrum disorder in taiwanese han population |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580585/ https://www.ncbi.nlm.nih.gov/pubmed/26398136 http://dx.doi.org/10.1371/journal.pone.0138695 |
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