Genome-wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders

Lu Xia; Jianjun Ou; Kuokuo Li; Hui Guo; Zhengmao Hu; Ting Bai; Jingping Zhao; Kun Xia; Fengyu Zhang

doi:10.1002/aur.2229

Genome-wide association analysis of autism identified multiple loci that have been reported as strong signals for neuropsychiatric disorders

Autism Res. 2020 Mar;13(3):382-396. doi: 10.1002/aur.2229. Epub 2019 Oct 24.

Authors

Lu Xia¹, Jianjun Ou², Kuokuo Li¹, Hui Guo¹, Zhengmao Hu¹, Ting Bai¹, Jingping Zhao², Kun Xia^{1

3

4}, Fengyu Zhang^{2

5

6}

Affiliations

¹ Center for Medical Genetics and Hunan Provincial Key Laboratory for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
² Mental Health Institute, The Second Xiangya Hospital, Central South University, Changsha, China.
³ CAS Center for Excellence in Brain Science and Intelligences Technology (CEBSIT), Shanghai, China.
⁴ Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan, China.
⁵ Global Clinical and Translational Research Institute, Bethesda, Maryland.
⁶ Peking University Huilongguan Clinical Medical School and Beijing Huilongguan Hospital, Beijing, China.

PMID: 31647196
DOI: 10.1002/aur.2229

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.

Keywords: autism; genome-wide association study; neuropsychiatric disorders; transmission disequilibrium test.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autism Spectrum Disorder / genetics*
Child, Preschool
Female
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study / methods*
Genotype
Humans
Male
Phenotype
Polymorphism, Single Nucleotide / genetics