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. 2015 Feb 6:5:8296.
doi: 10.1038/srep08296.

Association of genetic variants of GRIN2B with autism

Yongcheng Pan  1 , Jingjing Chen  1 , Hui Guo  2 , Jianjun Ou  3 , Yu Peng  1 , Qiong Liu  1 , Yidong Shen  3 , Lijuan Shi  3 , Yalan Liu  4 , Zhimin Xiong  5 , Tengfei Zhu  1 , Sanchuan Luo  1 , Zhengmao Hu  1 , Jingping Zhao  3 , Kun Xia  6
Affiliations

Association of genetic variants of GRIN2B with autism

Yongcheng Pan et al. Sci Rep. .

Abstract

Autism (MIM 209850) is a complex neurodevelopmental disorder characterized by social communication impairments and restricted repetitive behaviors. It has a high heritability, although much remains unclear. To evaluate genetic variants of GRIN2B in autism etiology, we performed a system association study of common and rare variants of GRIN2B and autism in cohorts from a Chinese population, involving a total sample of 1,945 subjects. Meta-analysis of a triad family cohort and a case-control cohort identified significant associations of multiple common variants and autism risk (Pmin = 1.73 × 10(-4)). Significantly, the haplotype involved with the top common variants also showed significant association (P = 1.78 × 10(-6)). Sanger sequencing of 275 probands from a triad cohort identified several variants in coding regions, including four common variants and seven rare variants. Two of the common coding variants were located in the autism-related linkage disequilibrium (LD) block, and both were significantly associated with autism (P < 9 × 10(-3)) using an independent control cohort. Burden analysis and case-only analysis of rare coding variants identified by Sanger sequencing did not find this association. Our study for the first time reveals that common variants and related haplotypes of GRIN2B are associated with autism risk.

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Figures

Figure 1
Figure 1. Regional association plot of a negative logarithm of combined P-values for GRIN2B common variants.
The most significant SNP was rs7970177 (P = 1.73E-04), which showed strong LD with its nearby five SNPs (r2 > 0.8). The six SNPs constructed a strong LD block and showed strong associations with autism (P = 1.78E-06).
Figure 2
Figure 2. Haplotype plot for the LD block constructed from 11 significant SNPs.
SNPs with blue squares were identified by Sanger sequencing and showed significant association. The six SNPs included by the black triangle (Block 1) constructed the most significant haplotype identified by sliding-window analysis.
See this image and copyright information in PMC

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