Genome‐wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders. Issue 3 (24th October 2019)

• Record Type: Journal Article
• Authors: Xia, Lu; Ou, Jianjun; Li, Kuokuo; Guo, Hui; Hu, Zhengmao; Bai, Ting; Zhao, Jingping; Xia, Kun; Zhang, Fengyu
• Is Part Of: Autism research. Volume 13:Issue 3(2020)
• Page Start: 382
• Page End: 396
• Publication Date: 2019-10-24
• Subjects: autism -- genome‐wide association study -- transmission disequilibrium test -- neuropsychiatric disorders; Autism -- Periodicals; Autism -- Research -- Periodicals; 616.85882005
• DOI: 10.1002/aur.2229
• Languages: English
• ISSNs: 1939-3792

Abstract

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.