scholarly journals DNA Methylation in LIME1 and SPTBN2 Genes Is Associated with Attention Deficit in Children

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 92
Author(s):  
Sung-Chou Li ◽  
Ho-Chang Kuo ◽  
Lien-Hung Huang ◽  
Wen-Jiun Chou ◽  
Sheng-Yu Lee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Attention Deficit ◽  
Performance Test ◽  
Neurodevelopmental Disorder ◽  
Continuous Performance Test ◽  
Attention Deficits ◽  
Clinical Settings ◽  
Hyperactivity Disorder ◽  
Cpg Sites ◽  
Healthy Control

DNA methylation levels are associated with neurodevelopment. Attention-deficit/hyperactivity disorder (ADHD), characterized by attention deficits, is a common neurodevelopmental disorder. We used methylation microarray and pyrosequencing to detect peripheral blood DNA methylation markers of ADHD. DNA methylation profiling data from the microarray assays identified potential differentially methylated CpG sites between 12 ADHD patients and 9 controls. Five candidate CpG sites (cg00446123, cg20513976, cg07922513, cg17096979, and cg02506324) in four genes (LIME1, KCNAB2, CAPN9, and SPTBN2) were further examined with pyrosequencing. The attention of patients were tested using the Conners’ Continuous Performance Test (CPT). In total, 126 ADHD patients with a mean age of 9.2 years (78.6% males) and 72 healthy control subjects with a mean age of 9.3 years (62.5% males) were recruited. When all participants were categorized by their CPT performance, the DNA methylation levels in LIME1 (cg00446123 and cg20513976) were found to be significantly higher and those in SPTBN2 (cg02506324) were significantly lower in children with worse CPT performance. Therefore, DNA methylation of two CpG sites in LIME1 and one CpG site in SPTBN2 is associated with attention deficits in children. DNA methylation biomarkers may assist in identifying attention deficits of children in clinical settings.

scholarly journals Exploring Genetic Variation that Influences Brain Methylation in Attention-Deficit/Hyperactivity Disorder

2018 ◽  
Author(s):  
Laura Pineda-Cirera ◽  
Anu Shivalikanjli ◽  
Judit Cabana-Domínguez ◽  
Ditte Demontis ◽  
Veera M. Rajagopal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorder ◽  
Epigenetic Mechanism ◽  
Brain Volumes ◽  
Altered Expression ◽  
Hyperactivity Disorder ◽  
Cpg Sites

ABSTRACTAttention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder caused by an interplay of genetic and environmental factors. Epigenetics is crucial to lasting changes in gene expression in the brain. Recent studies suggest a role for DNA methylation in ADHD. We explored the contribution to ADHD of allele-specific methylation (ASM), an epigenetic mechanism that involves SNPs correlating with differential levels of DNA methylation at CpG sites. We selected 3,896 tagSNPs reported to influence methylation in human brain regions and performed a case-control association study using the summary statistics from the largest GWAS meta-analysis of ADHD, comprising 20,183 cases and 35,191 controls. We identified associations with eight tagSNPs that were significant at a 5% False Discovery Rate (FDR). These SNPs correlated with methylation of CpG sites lying in the promoter regions of six genes. Since methylation may affect gene expression, we inspected these ASM SNPs together with 52 ASM SNPs in high LD with them for eQTLs in brain tissues and observed that the expression of three of those genes was affected by them. ADHD risk alleles correlated with increased expression (and decreased methylation) of ARTN and PIDD1 and with a decreased expression (and increased methylation) of C2orf82. Furthermore, these three genes were predicted to have altered expression in ADHD, and genetic variants in C2orf82 correlated with brain volumes. In summary, we followed a systematic approach to identify risk variants for ADHD that correlated with differential cis-methylation, identifying three novel genes contributing to the disorder.

scholarly journals Exploring genetic variation that influences brain methylation in attention-deficit/hyperactivity disorder

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Laura Pineda-Cirera ◽  
Anu Shivalikanjli ◽  
Judit Cabana-Domínguez ◽  
Ditte Demontis ◽  
Veera M. Rajagopal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorder ◽  
Epigenetic Mechanism ◽  
Altered Expression ◽  
Hyperactivity Disorder ◽  
Cpg Sites ◽  
Risk Variants

Abstract Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder caused by an interplay of genetic and environmental factors. Epigenetics is crucial to lasting changes in gene expression in the brain. Recent studies suggest a role for DNA methylation in ADHD. We explored the contribution to ADHD of allele-specific methylation (ASM), an epigenetic mechanism that involves SNPs correlating with differential levels of DNA methylation at CpG sites. We selected 3896 tagSNPs reported to influence methylation in human brain regions and performed a case-control association study using the summary statistics from the largest GWAS meta-analysis of ADHD, comprising 20,183 cases and 35,191 controls. We observed that genetic risk variants for ADHD are enriched in ASM SNPs and identified associations with eight tagSNPs that were significant at a 5% false discovery rate (FDR). These SNPs correlated with methylation of CpG sites lying in the promoter regions of six genes. Since methylation may affect gene expression, we inspected these ASM SNPs together with 52 ASM SNPs in high LD with them for eQTLs in brain tissues and observed that the expression of three of those genes was affected by them. ADHD risk alleles correlated with increased expression (and decreased methylation) of ARTN and PIDD1 and with a decreased expression (and increased methylation) of C2orf82. Furthermore, these three genes were predicted to have altered expression in ADHD, and genetic variants in C2orf82 correlated with brain volumes. In summary, we followed a systematic approach to identify risk variants for ADHD that correlated with differential cis-methylation, identifying three novel genes contributing to the disorder.

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