1.A Meta analysis of family risk factors for attention deficit hyperactivity disorder.
Chinese Journal of Contemporary Pediatrics 2015;17(7):721-725
OBJECTIVETo investigate the risk factors for attention deficit hyperactivity disorder (ADHD) and to provide a basis for future prevention and treatment of this disease.
METHODSFollowing a systematic search for case-control studies on the risk factors for ADHD in China between 2000 and 2014, relevant family risk factors were extracted accordingly. The quality of selected studies was evaluated according to the NOS scale. A Meta analysis on the selected studies was conducted using Stata 12.0 software.
RESULTSA total of 16 studies were selected, involving 2 167 children with ADHD and 2 148 normal controls. Results of Meta analysis showed that good parenting (OR=0.32, 95% CI: 0.26-0.40), nuclear family (OR=0.56, 95% CI: 0.41-0.76), high education level of father (OR=0.56, 95% CI: 0.41-0.76), high education level of mother (OR=0.65, 95% CI: 0.47-0.89), and extroversion of mother (OR=0.33, 95% CI: 0.18-0.61) are favorable factors for ADHD. Poor parental relationship (OR=1.90, 95% CI: 1.17-3.06) and family history of ADHD (OR=5.86, 95% CI: 3.67-9.35) are risk factors for ADHD.
CONCLUSIONSGood parenting, nuclear family, high education level of parents, and mother with extroversion are protective factors for ADHD, whereas poor parental relationship and family history of ADHD are associated with an increased risk for ADHD.
Attention Deficit Disorder with Hyperactivity ; etiology ; genetics ; Family ; Humans ; Risk Factors
2.Progress in genetic research on cognitive function of attention deficit hyperactivity disorder.
Chinese Journal of Medical Genetics 2018;35(6):912-915
Attention deficit hyperactivity disorder (ADHD) is a form of neuronal dysplasia featuring high hereditary (up to 76%). This paper reviews recent progress made in genetic research on the cognitive function in ADHD. Two aspects of cognitive function were explored from the perspective of genetics, including intelligence and executive function.
Attention Deficit Disorder with Hyperactivity
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genetics
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Cognition
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Executive Function
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Genetic Research
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Humans
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Intelligence
3.Correlation between ABO blood type gene and attention-deficit hyperactivity disorder in children.
Xian-Su GUO ; Bao-Quan JIAO ; Tong XU
Chinese Journal of Contemporary Pediatrics 2009;11(5):371-373
OBJECTIVETo investigate the correlation between ABO blood type gene and attention-deficit hyperactivity disorder (ADHD) in children.
METHODSABO blood types were determined using glass sheet method in 96 children with ADHD and their parents. O gene was identified using polymerase chain reaction and restriction fragment length polymorphism in patients with A or B blood type. Haplotype-based haplotype relative risk (HHRR), transmission-disequilibrium test (TDT) and Chi-square test were used to examine the association between ABO gene and ADHD.
RESULTSTDT results showed significant differences in the allele of ABO between the 96 children with ADHD and within-family controls (chi2=6.017, df=2, P< 0.05). Chi-square test results showed differences in the allele of A and B (chi2=3.289, df=1, P=0.07) as well as O and B (chi2=3.629, df=1, P=0.057 ) between ADHD children and within-family controls. The frequencies of O and A genes were higher than that of B gene in ADHD children.
CONCLUSIONSThere was correlation between ABO blood type gene and ADHD in children. The risk of ADHD is increased in the presence of alleles O and A, but the risk is reduced in the presence of allele B.
ABO Blood-Group System ; genetics ; Adolescent ; Alleles ; Attention Deficit Disorder with Hyperactivity ; blood ; genetics ; Child ; Female ; Haplotypes ; Humans ; Male
4.Exploration of common biological pathways for attention deficit hyperactivity disorder and low birth weight.
Bo XIANG ; Minglan YU ; Xuemei LIANG ; Wei LEI ; Chaohua HUANG ; Jing CHEN ; Wenying HE ; Tao ZHANG ; Tao LI ; Kezhi LIU
Chinese Journal of Medical Genetics 2017;34(6):844-848
OBJECTIVETo explore common biological pathways for attention deficit hyperactivity disorder (ADHD) and low birth weight (LBW).
METHODSThei-Gsea4GwasV2 software was used to analyze the result of genome-wide association analysis (GWAS) for LBW (pathways were derived from Reactome), and nominally significant (P< 0.05, FDR< 0.25) pathways were tested for replication in ADHD.Significant pathways were analyzed with DAPPLE and Reatome FI software to identify genes involved in such pathways, with each cluster enriched with the gene ontology (GO). The Centiscape2.0 software was used to calculate the degree of genetic networks and the betweenness value to explore the core node (gene). Weighed gene co-expression network analysis (WGCNA) was then used to explore the co-expression of genes in these pathways.With gene expression data derived from BrainSpan, GO enrichment was carried out for each gene module.
RESULTSEleven significant biological pathways was identified in association with LBW, among which two (Selenoamino acid metabolism and Diseases associated with glycosaminoglycan metabolism) were replicated during subsequent ADHD analysis. Network analysis of 130 genes in these pathways revealed that some of the sub-networksare related with morphology of cerebellum, development of hippocampus, and plasticity of synaptic structure. Upon co-expression network analysis, 120 genes passed the quality control and were found to express in 3 gene modules. These modules are mainly related to the regulation of synaptic structure and activity regulation.
CONCLUSIONADHD and LBW share some biological regulation processes. Anomalies of such proces sesmay predispose to ADHD.
Attention Deficit Disorder with Hyperactivity ; etiology ; genetics ; Gene Ontology ; Gene Regulatory Networks ; Genome-Wide Association Study ; Humans ; Infant, Low Birth Weight
5.Latest Updates on Molecular Genetics and Pharmacogenomic Study in Child and Adolescent Psychiatric Field.
Journal of Korean Neuropsychiatric Association 2007;46(4):295-307
The objective of this article is to review the literature over the past decade on the molecular genetic studies and pharmacogenomic studies in child and adolescent psychiatric disorders. A computerized search was done for articles published in the past decade, and selected papers are highlighted. The past decade of research has illuminated molecular genetic studies of attention deficit hyperactivity disorder (ADHD), Tourette's disorder and autism spectrum disorder. Advances in statistical methodologies and laboratory-based gene-hunting techniques are laying the foundation for a deeper understanding of genetics that contribute to these disorders. In addition, pharmacogenomic studies of ADHD, which has mostly been done in child and adolescent psychiatric field, were reviewed in this article. ADHD is well demonstrated in clinical trials to have substantial number of patients fail to remain on therapy, and there is tremendous variability in tolerability and treatment acceptance. The majority investigated the role of candidate genes in predicting clinical response to methylphenidate. The most frequently studied is DAT1, although findings are inconsistent, with the 10-repeat polymorphism predicting both increased and decreased symptom reduction in various reports. Other candidates include DRD4, DRD5, DBH, 5HTT, SNAP-25 and COMT. Although interest in ADHD pharmacogenomics is encouraging, preliminary studies have been limited by small sample sizes, inconsistent research designs, retrospective reports and a focus on symptom response. Future studies should emphasize large, prospective trials, assess multiple medications in individual subjects and consider a full range of pharmacodynamic and pharmacokinetic outcomes.
Adolescent*
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Attention Deficit Disorder with Hyperactivity
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Autism Spectrum Disorder
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Child*
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Genetics
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Humans
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Methylphenidate
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Molecular Biology*
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Pharmacogenetics
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Research Design
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Sample Size
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Tourette Syndrome
6.Association between serotonin 2C gene polymorphisms and attention deficit hyperactivity disorder in children with or without comorbidity of disruptive behavior disorder.
Jun LI ; Yu-feng WANG ; Ru-lun ZHOU ; Li YANG ; Hao-bo ZHANG ; Bing WANG
Chinese Journal of Pediatrics 2007;45(5):374-377
OBJECTIVEDisruptive behavior disorder (DBD) is one of the main comorbidity of attention deficit hyperactivity disorder (ADHD). Previous studies showed significantly different serotonin function between ADHD children with and without the comorbidity of DBD. Therefore, it is needed to compare these two groups in terms of serotonin receptor gene polymorphisms, which may provide further evidence for the previous studies. The current study aimed to investigate the relationship between two serotonin receptor 2C (HTR2C) gene polymorphisms, that are C-759T and G-697C polymorphisms, and ADHD with or without concomitant DBD.
METHODBlood samples were taken from 237 trios with probands of ADHD with DBD comorbidity and 251 trios with probands of ADHD without comorbidity of DBD. All the subjects were from the ADHD clinic of Peking University Sixth Hospital. DNA was extracted and PCR was performed to amplify the fragments containing both C-759T and G-697C polymorphisms. AciI was used to detect different alleles of the two polymorphisms. Both allele-based and haplotype-based TDT analyses were used to test the association of the two polymorphisms of HTR2C gene and ADHD with or without comorbidity of DBD.
RESULTSThe haplotypes -759C (chi(2) = 4.25, P = 0.04), -697G(chi(2) = 3.21, P = 0.07), as well as -759C/-697G were over-transmitted (chi(2) = 4.31, P = 0.04) to the probands of ADHD without DBD. No biased transmission of any allele and haplotype were found in families with probands of ADHD with DBD.
CONCLUSIONADHD with or without the comorbidity DBD was different at the level of HTR2C gene polymorphisms of C-759T and G-697C. HTR2C is related to ADHD without DBD, while not related to ADHD with DBD. The results suggested that the two groups may have different genetic background, at least in HTR2C.
Alleles ; Attention Deficit Disorder with Hyperactivity ; complications ; genetics ; Attention Deficit and Disruptive Behavior Disorders ; complications ; genetics ; Child ; Comorbidity ; Gene Frequency ; Genetic Predisposition to Disease ; Genetic Testing ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Polymorphism, Genetic ; Receptor, Serotonin, 5-HT2C ; genetics ; Receptors, Serotonin ; Serotonin ; genetics
7.Association of CLOCK gene T3111C polymorphism with attention deficit hyperactivity disorder and related sleep disturbances in children.
Yin-Li CAO ; Qin-Tao CUI ; Cheng-He TANG ; Xiao CHANG
Chinese Journal of Contemporary Pediatrics 2012;14(4):285-288
OBJECTIVETo examine the association between CLOCK gene T3111C polymorphism with attention deficit hyperactivity disorder (ADHD) and ADHD related sleep disturbances in children.
METHODSOne hundred and sixty-six unrelated children with ADHD diagnosed according to DSM-IV criteria and a control group of 150 normal children were enrolled in this study. Parents filled out the Sleep Disturbance Scale for Children (SDSC). Genotype and allele frequencies of T3111C of the CLOCK gene were examined by PCR-restriction fragment length polymorphisms (PCR-RFLP).
RESULTSThere were significant differences in the genotype and allele frequencies of T3111C of the CLOCK gene between the ADHD and control groups (P<0.05). C allele frequency in the ADHD group was significantly higher than in the control group (χ2=7.254, P=0.007, OR=1.740, 95%CI=1.160-2.612). The ADHD children with sleep disturbances were found to have higher C allele frequency than those without sleep disturbances (χ2=13.052, P<0.001, OR=2.766, 95%CI=1.573-4.865).
CONCLUSIONSThere is an association between CLOCK gene T3111C polymorphism and both ADHD and related sleep disturbances in children. The individuals with C allele are susceptible to ADHD as well as ADHD related sleep disturbances.
Adolescent ; Attention Deficit Disorder with Hyperactivity ; complications ; genetics ; CLOCK Proteins ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Male ; Polymorphism, Genetic ; Sleep Wake Disorders ; etiology ; genetics
8.Dopamine Transporter Genotype Influences the Attention Deficit in Korean Boys with ADHD.
Kang Seob OH ; Dong Won SHIN ; Guk Taek OH ; Kyung Sun NOH
Yonsei Medical Journal 2003;44(5):787-792
Attention appears to be inheritable, stable and influenced by genetic factors. The use of the Continuous Performance Test (CPT), as an endophenotypic measure, is valuable for genetic studies because it may show increased sensitivity to specific dimensions in attention deficit hyperactivity disorder. However, few studies have been designed to examine the influence of the genotype on attention level measured by CPT in ADHD patients. This study examinee the difference between 10/10 and 10/* genotype in the attention deficits measured by the CPT in ADHD patients. Forty-four unrelated ADHD patients were recruited from the psychiatric outpatients' clinic at Kangbuk Samsung Hospital. Two child psychiatrists made the diagnoses of ADHD using the DSM-IV diagnostic criteria. The genomic DNA was extracted from the blood, and analyzed to determine the genotype. A 40-base pair variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region was amplified. The attention deficits were measured by the test of variables of attention (T.O.V.A.). Between the 10/10 genotype and 10/* genotype, standard scores of the T.O.V.A were compared using a Mann-Whiney test. A comparison with the 10/10 genotype and 10/* genotype showed that those patients with the 10/10 genotype made less omission errors in the first quarter of the test (p < 0.05, by Mann-Whiney test). No significant differences were observed in the errors of commission, response time, variability. This study found that the 10/10 genotype made less omission errors on the T.O.V.A. This suggests that the dopamine transporter genotype influences the attention deficits measured by T.O.V.A.
3' Untranslated Regions/genetics
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Alleles
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Attention Deficit Disorder with Hyperactivity/*genetics
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Child
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Child, Preschool
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Genotype
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Human
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Male
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Membrane Transport Proteins/*genetics
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Minisatellite Repeats
9.Association between SNAP-25 gene polymorphism and attention deficit hyperactivity disorder.
Hong-yu ZHANG ; Yan-bo ZHU ; Hong CHANG ; Jia-chang CHEN
Chinese Journal of Pediatrics 2008;46(8):564-569
OBJECTIVETo analyse the association between polymorphism in human synaptosomal-associated protein of 25 000 (SNAP-25) gene and attention deficit hyperactivity disorder (ADHD) in Han Chinese children.
METHODSThe study samples were comprised of 100 integrated ADHD trios (included proband and biological parents) and 97 unrelated controls. Association of polymorphism with ADHD and its subtype was examined by: (1) comparing cases and controls; (2) using family-based association study in transmission disequilibrium test (TDT).
RESULTSCase-control analysis of short tandem repeat (STR) showed that there was no significant difference between the two groups in allele gene frequency and genotype frequency (P > 0.05); TDT analysis of the rs363006 SNP and the rs362549 SNP revealed no association between SNAP-25 polymorphisms and ADHD (P > 0.05). But after a stratification by ADHD subtype, the rs362549 SNP A allele showed a tendency to preferentially transmitted to ADHD-I subtype (chi(2) = 8.00, P < 0.01); and the rs362549 SNP G allele had a tendency to preferentially transmitted to ADHD-C subtype (chi(2) = 4.122, P < 0.05).
CONCLUSIONSNo association was found between SNAP-25 polymorphisms and ADHD. There was a possible association between rs362549 SNP polymorphism and ADHD subtypes, but the findings require replication before drawing a definitive conclusion.
Adolescent ; Alleles ; Attention Deficit Disorder with Hyperactivity ; genetics ; Case-Control Studies ; Child ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Microsatellite Repeats ; Polymorphism, Single Nucleotide ; Synaptosomal-Associated Protein 25 ; genetics
10.Catechol-O-methyltransferase gene rs6267 polymorphism in children with attention deficit hyperactivity disorder.
Yue-Bing ZHANG ; Xue-Rong LUO ; Xia LIU ; Yan ZHONG ; Feng ZHU ; Lei-Yin CHEN
Chinese Journal of Contemporary Pediatrics 2011;13(2):127-130
OBJECTIVETo study the relationship between rs6267 polymorphism of catechol-O-methyltransferase (COMT) gene and attention deficit hyperactivity disorder (ADHD).
METHODSOne hundred and fourteen children with ADHD and 76 normal volunteers were enrolled. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques were used for detecting COMT rs6267 polymorphism. The behavioral problems were assessed by Child Behavior Checklist (CBCL).
RESULTSThere were no significant differences in the COMT genotype distribution and allele frequencies between the ADHD and normal control groups. The frequencies of thinking problems (1.7±1.9 vs 1.0±0.9) and disciplinary problems (4.5±3.7 vs 2.2±1.4) in ADHD children carrying genotype G/G were significantly higher than those in children carrying G/T (P<0.05).
CONCLUSIONSCOMT rs6267 polymorphism may not contribute to susceptibility to ADHD. However, there might be an association between rs6267 polymorphism and some clinical characters of ADHD.
Adolescent ; Attention Deficit Disorder with Hyperactivity ; genetics ; Catechol O-Methyltransferase ; genetics ; Child ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Polymorphism, Genetic