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

Abstract

BackgroundAutism 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.MethodsA 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.ResultsSeven 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.ConclusionsWe 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.

Whole‑exome sequencing of lobular endocervical glandular hyperplasia

“…KPRP is an epidermal marker of differentiating keratinocytes, and its expression is elevated in psoriatic lesions (24). Regarding OR2M4, this olfactory receptor protein is one of the members of a large family of G-protein-coupled receptors, the signaling pathways of which are important for autism spectrum disorder (25). Furthermore, ZNF645, a human RING finger protein, possesses the domain of E3 ubiquitin ligase activity (26).…”

Autism genetics – an overview

“…14 Overall, in the past half-decade of using this method, about 20 common variants have been identified. [15][16][17][18][19][20] However, the fact that several GWASs failed to identify any loci of genome-wide significance, 21,22 despite using genetic data from more than 1000 families affected with autism, suggests that the effect size of singular common variants is relatively small.…”

GLIS1-3: emerging roles in reprogramming, stem and progenitor cell differentiation and maintenance

“…Beyond its role in reprogramming, relatively little is known about the biological functions of GLIS1 (29). GWAS studies reported an association between SNPs in GLIS1 and increased risk of autism spectrum disorder and Alzheimer's disease (30,31).…”