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Abstract：
Autism is a common neurodevelopmental disorder with a moderate to a high degree of heritability, but only a few common genetic variants that explain the heritability have been associated. We performed a genome-wide transmission disequilibrium test analysis of a newly genotyped autism case-parent triad samples (127 trios) in Han Chinese, identified top association signals at multiple single nucleotide polymorphisms (SNPs), including rs9839376 (OR = 2.59, P = 1.27 × 10-05 ) at KCNMB2, rs6044680 (OR = 0.319, P = 4.82 × 10-05 ) and rs7274133 (OR = 0.313, P = 3.22 × 10-05 ) at PCSK2, and rs310619 (OR = 2.40, P = 7.44 × 10-05 ) at EEF1A2. Furthermore, a genome-wide combined P-value of individual SNPs in two independent case-parent triad samples (total 402 triads, n = 1,206) identified SNPs at EGFLAM, ZDHHC2, AGBL1, and SNX29 as additional association signals for autism. While none of these signals achieved a genome-wide significance in the two samples of our study, they have been reported in a previous genome-wide association study of neuropsychiatric disorders, and the majority of these SNP have a significant cis-regulatory association with mRNA in human tissues (false discovery rate (FDR) < 0.05). Our study warrants further study or replication with additional sample for association with autism and other neuropsychiatric disorders. Autism Res 2020, 13: 382-396. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism is a common neurodevelopmental disorder, heritable, but only a few common genetic variants that explain the heritability have been associated. We conducted a genome-wide association study with two cohorts of autism case-parent triad samples in Han Chinese and identified multiple single nucleotide polymorphisms that were reported as strong association signals in a previous genome-wide association study of other neuropsychiatric disorders or related traits. Our study provides evidence for shared genetic variants among autism and other neuropsychiatric disorders.
摘要：
自闭症是一种常见的神经发育障碍，具有中等至高度的遗传性，但是只有少数常见的遗传变异可以解释遗传力。我们对汉族人新基因分型的自闭症病例-父母三联征样本（127个三联征）进行了全基因组传播不平衡测试分析，在多个单核苷酸多态性（SNP）确定的最高关联信号，包括KCNMB2的rs9839376（OR=2.59，P=1.27×10-05），rs6044680（OR=0.319，P=4.82×10-05）和rs7274133（OR=0.313，P=3.22×10-05）在PCSK2，rs310619（OR=2.40，P=7.44×10-05）。此外，两个独立的病例-亲本三联体样本中单个SNP的全基因组组合P值(总共402个三联体，n=1,206)在EGFLAM鉴定出SNP，ZDHC2，AGBL1和SNX29作为自闭症的其他关联信号。虽然这些信号在我们研究的两个样本中都没有达到全基因组意义，在先前的神经精神疾病的全基因组关联研究中已经报道了它们，并且这些SNP中的大多数与人组织中的mRNA具有显著的顺式调控关联(错误发现率(FDR)<0.05)。我们的研究值得进一步研究或复制与自闭症和其他神经精神疾病相关的额外样本。自闭症Res2020，13：382-396。©2019国际自闭症研究学会，Wiley期刊,公司。LAY总结：自闭症是一种常见的神经发育障碍，可遗传，但是只有少数常见的遗传变异可以解释遗传力。我们对中国汉族人自闭症病例-父母三联症样本的两个队列进行了全基因组关联研究，并鉴定了多个单核苷酸多态性，这些多态性在先前的其他神经精神疾病或相关性状的全基因组关联研究中被报道为强关联信号。我们的研究提供了自闭症和其他神经精神疾病之间共有遗传变异的证据。
