. 2015 Sep 23;10(9):e0138695.

doi: 10.1371/journal.pone.0138695. eCollection 2015.

Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population

Po-Hsiu Kuo¹, Li-Chung Chuang², Mei-Hsin Su³, Chia-Hsiang Chen⁴, Chien-Hsiun Chen⁵, Jer-Yuarn Wu⁵, Chung-Jen Yen⁶, Yu-Yu Wu⁷, Shih-Kai Liu⁸, Miao-Chun Chou⁹, Wen-Jiun Chou⁹, Yen-Nan Chiu¹⁰, Wen-Che Tsai¹⁰, Susan Shur-Fen Gau¹¹

Affiliations

¹ 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.
² Department of Nursing, Cardinal Tien Junior College of Healthcare & Management, I-Lan, Taiwan.
³ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁴ Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan; Department and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
⁵ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
⁶ Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
⁷ Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan.
⁸ Department of Child and Adolescent Psychiatry, Taoyaun Psychiatric Center, Ministry of Health and Welfare, Taoyuan, Taiwan.
⁹ Department of Child Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
¹⁰ Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
¹¹ 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.

PMID: 26398136
PMCID: PMC4580585
DOI: 10.1371/journal.pone.0138695

Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population

Po-Hsiu Kuo et al. PLoS One. 2015.

. 2015 Sep 23;10(9):e0138695.

doi: 10.1371/journal.pone.0138695. eCollection 2015.

Authors

Affiliations

¹ 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.
² Department of Nursing, Cardinal Tien Junior College of Healthcare & Management, I-Lan, Taiwan.
³ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁴ Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan; Department and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
⁵ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
⁶ Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
⁷ Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan.
⁸ Department of Child and Adolescent Psychiatry, Taoyaun Psychiatric Center, Ministry of Health and Welfare, Taoyuan, Taiwan.
⁹ Department of Child Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
¹⁰ Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
¹¹ 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.

PMID: 26398136
PMCID: PMC4580585
DOI: 10.1371/journal.pone.0138695

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

**Fig 1. Manhattan plot of genome-wide association analysis.**
Results of genome-wide association analysis (–log₁₀P) are shown in chromosomal order for 546,171 SNPs that were tested for association in the initial sample of 315 ASD cases and 1115 controls. The horizontal line indicates a P-value of 10⁻⁵.

**Fig 2. Locus-plot of reported associated gene regions for ASD.**
(A) *OR2M3_OR2T5*. (B) *STYK1*. (C) *SGSM2_MNT*. (D) *GLIPR1_KRR*. (E) *GLIS1*. (F) *NAALADL2*.

See this image and copyright information in PMC

References

1. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders Arlington, VA: American Psychiatric Publishing.
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Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population

Affiliations

Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

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LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical