Association between genetic variants in SLC25A12 and risk of autism spectrum disorders: An integrated meta‐analysis

Abstract

The solute carrier family 25 (aspartate/glutamate carrier), member 12 gene (SLC25A12) has been strongly posed as a candidate gene for autism spectrum disorder (ASD) given its important role in mitochondrial function and adenosine triphosphate (ATP) synthesis. Evidence is mounting for the association between SLC25A12 variants (rs2056202 and rs2292813) and ASD risk, but the results are inconsistent. To clarify the effect of these two variants on ASD, a meta-analysis integrating case-control and transmission disequilibrium test (TDT) studies was performed. The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature (CBM), Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies published up to May 2014. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to assess the strength of association. A total of 775 cases, 922 controls, and 1289 families available from 8 studies concerning rs2056202, and 465 cases, 450 controls, and 1516 families available from 7 studies concerning rs2292813 were finally included. In the overall meta-analysis, the rs2056202 T allele and rs2292813 T allele were both significantly associated with a decreased risk of ASD (rs2056202: OR = 0.809, P = 0.001, 95%CI: 0.713-0.917, I(2) = 0.0%, and P(heterogeneity) = 0.526; rs2292813: OR = 0.752, P < 0.001, 95%CI: 0.649-0.871, I(2) = 0.0%, P(heterogeneity) = 0.486). Besides, subjects with T-T haplotype of rs2056202-rs2292813 had a significantly reduced risk of ASD (OR = 0.672, P < 0.001, 95%CI: 0.564-0.801, I(2) = 0.0%, P(heterogeneity) = 0.631). Sensitivity analysis, cumulative meta-analysis, and publication bias diagnostics confirmed the reliability and stability of our results. Our meta-analysis suggests that rs2056202 and rs2292813 in SLC25A12 may contribute significantly to ASD risk.

Genetic Variation and Autism: A Field Synopsis and Systematic Meta-Analysis

“…Out of the remaining six articles, two were already in our dataset from the literature search from PubMed. Finally, four articles from the GWAS catalog were manually added to 27 articles previously screened from PubMed, leading to a total of 31 eligible articles [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ] being included in the systematic review ( Figure 1 ).…”

“…In terms of BFDP, five (16.1%) and two (6.5%) comparisons had noteworthy findings (<0.8) at a prior probability of 10 −3 and 10 −6 . Two single nucleotide polymorphisms (SNPs) were found to be noteworthy under FPRP estimation only, and not under BFDP (Comparison T vs. C, SLC25A12/rs2292813 [ 20 ]; C vs. T, SLC25A12/rs2292813 [ 24 ]). In contrast, none of the SNPs were identified to be noteworthy exclusively under BFDP.…”

A Study of Genetic Variants in Genes of Glutamate Signaling and Risk of Childhood Autism Spectrum Disorder

“…Several studies conducted one decade ago reported an association between ASD and SNPs rs2292813, rs2056202 [30][31][32] and rs908670 [33] in the SLC25A12 gene, though a few others found no association between ASD and these SNPs [34,35], including one study conducted within a Han population in Taiwan [18]. Two Recent meta-analyses, including one from our group, summarized studies published before 2014 and both concluded a strong association between SNPs rs2056202 and rs2292813 and ASD [20,36]. With a smaller sample size, we have previously demonstrated a positive association with rs2056202 and rs2292813 and the risk of ASD [22].…”

Association study and a systematic meta-analysis of the VNTR polymorphism in the 3′-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder

“…The current study included the largest sample size available (total n = 40,681 consisting of 14,821 cases) for a powerful meta-analysis of the DAT1 3′-UTR VNTR gene variants, and used when needed the random-effects model that incorporate heterogeneity among trials (Borenstein et al 2010 ). Indeed, following quality assessment of all included studies according to traditional epidemiological considerations (Liu et al 2015 ) indicated that some studies did not reach high quality scores due to sample size, diagnostic criteria, recruitment strategies and quality control of the genetic analysis. This was reflected in significant heterogeneity, that in some cases, was also confirmed with significant publication bias assessed with Begg’s test (Begg and Mazumdar 1994 ) and Egger’s regression test (Egger et al 1997 ).…”

“…The quality of all included studies was assessed based on traditional epidemiological considerations for genetic studies as previously described in Liu et al ( 2015 ; Supplementary Table S1). The meta-analysis was conducted using the MIX 2.0-Professional software for meta-analysis in Excel, version 2.0.1.6 ( http://www.meta-analysis-made-easy.com/ ) (Bax et al 2006 ).…”