Common genetic variants on 1p13.2 associate with risk of autism

K Xia; H Guo; G Xun; L Zuo; Y Peng; Y He; Z Xiong; L Sun; Q Pan; Z Long; X Zou; L Lu; Y Liu; D Tian; L Long; Y Liu; H Peng; X Luo; W Su; D Liang; H Dai; X Yan; Y Feng; B Tang; Z Miedzybrodzka; J Xia; Z Zhang; X Luo; X Zhang; D St Clair; J Zhao; F Zhang

doi:10.1038/mp.2013.146

Common genetic variants on 1p13.2 associate with risk of autism

K Xia, H Guo, G Xun, L Zuo, Y Peng, Y He, Z Xiong, L Sun, Q Pan, Z Long, X Zou, L Lu, Y Liu, D Tian, L Long, Y Liu, H Peng, X Luo, W Su, D LiangH Dai, X Yan, Y Feng, B Tang, Z Miedzybrodzka, J Xia, Z Zhang, X Luo, X Zhang, D St Clair, J Zhao, F Zhang

Research output: Contribution to journal › Article › peer-review

71 Citations (Scopus)

Abstract

Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8.70 × 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.

Original language	English
Pages (from-to)	1212-1219
Number of pages	8
Journal	Molecular Psychiatry
Volume	19
Issue number	11
DOIs	https://doi.org/10.1038/mp.2013.146
Publication status	Published - Nov 2014

Keywords

African Americans
Asian Continental Ancestry Group
Autistic Disorder
China
Chromosomes, Human, Pair 1
Cohort Studies
DNA-Binding Proteins
European Continental Ancestry Group
GTP Phosphohydrolases
Genetic Predisposition to Disease
Genome-Wide Association Study
Haplotypes
Humans
Membrane Proteins
Meta-Analysis as Topic
Polymorphism, Single Nucleotide
Prefrontal Cortex
RNA-Binding Proteins
Risk
Transcription Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/mp.2013.146

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Xia, K, Guo, H, Xun, G, Zuo, L, Peng, Y, He, Y, Xiong, Z, Sun, L, Pan, Q, Long, Z, Zou, X, Lu, L, Liu, Y, Tian, D, Long, L, Liu, Y, Peng, H, Luo, X, Su, W, Liang, D, Dai, H, Yan, X, Feng, Y, Tang, B, Miedzybrodzka, Z, Xia, J, Zhang, Z, Luo, X, Zhang, X, St Clair, D, Zhao, J & Zhang, F 2014, 'Common genetic variants on 1p13.2 associate with risk of autism', Molecular Psychiatry, vol. 19, no. 11, pp. 1212-1219. https://doi.org/10.1038/mp.2013.146

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title = "Common genetic variants on 1p13.2 associate with risk of autism",

abstract = "Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8.70 × 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.",

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author = "K Xia and H Guo and G Xun and L Zuo and Y Peng and Y He and Z Xiong and L Sun and Q Pan and Z Long and X Zou and L Lu and Y Liu and D Tian and L Long and Y Liu and H Peng and X Luo and W Su and D Liang and H Dai and X Yan and Y Feng and B Tang and Z Miedzybrodzka and J Xia and Z Zhang and X Luo and X Zhang and {St Clair}, D and J Zhao and F Zhang",

year = "2014",

month = nov,

doi = "10.1038/mp.2013.146",

language = "English",

volume = "19",

pages = "1212--1219",

journal = "Molecular Psychiatry",

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T1 - Common genetic variants on 1p13.2 associate with risk of autism

AU - Xia, K

AU - Guo, H

AU - Xun, G

AU - Zuo, L

AU - Peng, Y

AU - He, Y

AU - Xiong, Z

AU - Sun, L

AU - Pan, Q

AU - Long, Z

AU - Zou, X

AU - Lu, L

AU - Liu, Y

AU - Tian, D

AU - Long, L

AU - Liu, Y

AU - Peng, H

AU - Luo, X

AU - Su, W

AU - Liang, D

AU - Dai, H

AU - Yan, X

AU - Feng, Y

AU - Tang, B

AU - Miedzybrodzka, Z

AU - Xia, J

AU - Zhang, Z

AU - Luo, X

AU - Zhang, X

AU - St Clair, D

AU - Zhao, J

AU - Zhang, F

PY - 2014/11

Y1 - 2014/11

N2 - Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8.70 × 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.

AB - Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8.70 × 10(-8)), and related haplotypes, AMPD1-NRAS-CSDE1, TRIM33 and TRIM33-BCAS2, associated with autism; all were mapped to a previously reported linkage region (1p13.2) with autism. These genetic associations were further supported by a cis-acting regulatory effect on the gene expressions of CSDE1, NRAS and TRIM33 and by differential expression of CSDE1 and TRIM33 in the human prefrontal cortex of post-mortem brains between subjects with and those without autism. Our study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism.

KW - African Americans

KW - Asian Continental Ancestry Group

KW - Autistic Disorder

KW - China

KW - Chromosomes, Human, Pair 1

KW - Cohort Studies

KW - DNA-Binding Proteins

KW - European Continental Ancestry Group

KW - GTP Phosphohydrolases

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Haplotypes

KW - Humans

KW - Membrane Proteins

KW - Meta-Analysis as Topic

KW - Polymorphism, Single Nucleotide

KW - Prefrontal Cortex

KW - RNA-Binding Proteins

KW - Risk

KW - Transcription Factors

U2 - 10.1038/mp.2013.146

DO - 10.1038/mp.2013.146

M3 - Article

C2 - 24189344

SN - 1359-4184

VL - 19

SP - 1212

EP - 1219

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 11

ER -

Common genetic variants on 1p13.2 associate with risk of autism

Abstract

Keywords

UN SDGs

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