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1.
Das M Das Bhowmik A Bhaduri N Sarkar K Ghosh P Sinha S Ray A Chatterjee A Mukhopadhyay K 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(2):577-587
Associations between attention deficit hyperactivity disorder (ADHD) and genetic polymorphisms in the dopamine receptors, transporter and metabolizing enzymes have been reported in different ethnic groups. Gene variants may affect disease outcome by acting synergistically or antagonistically and thus their combined effect becomes an important aspect to study in the disease etiology. In the present investigation, interaction between ten functional polymorphisms in DRD4, DAT1, MAOA, COMT, and DBH genes were explored in the Indo-Caucasoid population. ADHD cases were recruited based on DSM-IV criteria. Peripheral blood samples were collected from ADHD probands (N = 126), their parents (N = 233) and controls (N = 96) after obtaining informed written consent for participation. Genomic DNA was subjected to PCR based analysis of single nucleotide polymorphisms and variable number of tandem repeats (VNTRs). Data obtained was examined for population as well as family-based association analyses. While case-control analysis revealed higher occurrence of DAT1 intron 8 VNTR 5R allele (P = 0.02) in cases, significant preferential transmission of the 7R-T (DRD4 exon3 VNTR-rs1800955) and 3R-T (MAOA-u VNTR-rs6323) haplotypes were noticed from parents to probands (P = 0.02 and 0.002 respectively). Gene-gene interaction analysis revealed significant additive effect of DBH rs1108580 and DRD4 rs1800955 with significant main effects of DRD4 exon3 VNTR, DAT1 3′UTR and intron 8 VNTR, MAOA u-VNTR, rs6323, COMT rs4680, rs362204, DBH rs1611115 and rs1108580 thereby pointing towards a strong association of these markers with ADHD. Correlation between gene variants, high ADHD score and low DBH enzymatic activity was also noticed, especially in male probands. From these observations, an impact of the studied sites on the disease etiology could be speculated in this ethnic group. 相似文献
2.
Bhowmik AD Chaudhury S Dutta S Shaw J Chatterjee A Choudhury A Saha A Sadhukhan D Kar T Sinha S Mukhopadhyay K 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(7):1714-1722
Intellectual disability (ID) is of major concern throughout the world, though in ~ 40% of cases etiology remains unknown (idiopathic ID or IID). Cognitive impairment and behavioral problems are of common occurrence in these subjects and dopamine is known to play an important role in regulating these traits. In the present study the role of functional polymorphisms in three dopaminergic genes, dopamine receptor D4 (DRD4: exon3 VNTR and rs1800955), dopamine transporter (DAT1: 3′UTR VNTR and intron8 VNTR) and catechol-O-methyl transferase (COMT: rs4680 and rs165599), was explored in IID. Probands (n = 225), parents (n = 298) and ethnically matched controls (n = 175) were recruited following DSM-IV. Genotype data obtained was used for population- and family-based statistical analyses. Population-based analysis showed significant association of DRD4 exon3 VNTR 6R allele (P = 0.01), DAT1 3′UTR VNTR lower repeat (6R and 7R) alleles (P < 0.02) and intron8 VNTR 5R allele (P = 0.0012) with IID. Stratified analysis revealed significant association of these alleles (P < 0.05) with IID individuals exhibiting severe behavioral problems. On the other hand, preferential transmission of COMT rs4680 A allele and A-A haplotype (P < 0.05) was observed specifically in male IID probands without any behavioral problem. Markers failed to show any significant epistatic interaction by MDR analysis. Alleles showing positive association were all reported to confer suboptimal activity to the transcribed proteins. Therefore, an alteration in dopaminergic neurotransmission could be predicted that may lead to impairments in cognition and behavioral problems. 相似文献
3.
Mingqing Xu Qinghe Xing Sheng Li Yonglan Zheng Shengnan Wu Rui Gao Lan Yu Tingwei Guo Yifeng Yang Jixia Liu Aiping Zhang Xinzhi Zhao Guang He Jian Zhou Lei Wang Jiekun Xuan Jing Du Xingwang Li Guoyin Feng Zhiguang Lin Yifeng Xu David St Clair Zhicheng Lin Lin He 《Progress in neuro-psychopharmacology & biological psychiatry》2010
A number of studies have investigated the effectiveness of the dopamine transporter (SLC6A3) Gene as an antipsychotic target. However, the focus has mainly been on a 40-bp variable number of a tandem repeat (VNTR) in the 3′-region and results have been inconsistent. To fully evaluate SLC6A3 as a therapeutic antipshycotic target we investigated association of the gene with responses to chlorpromazine and clozapine and with chlorpromazine-induced extrapyramidal syndrome (EPS) in the Chinese schizophrenia population. Six polymorphisms across the whole region of this gene were analyzed, namely rs2652511 (T-844C) and rs2975226 (T-71A) in the 5′-regulatory region, rs2963238 (A1491C) in intron 1, a 30-bp VNTR in intron 8, rs27072 and the 40-bp VNTR in the 3′-region. We found that the polymorphic marker, rs2975226, showed significant association of allele and genotype frequencies with response to clozapine (allele-wise: adjusted p = 0.00404; genotype-wise: adjusted p = 0.024), and that patients with the T allele had a better response to the drug. The haplotype block constructed from the first three markers near the 5′-region showed significant association with response to clozapine (for haplotype T-T-A: p = 0.0085; for haplotype C-A-C: p = 0.0092). We did not identify any significant association of the six genetic variants or haplotypes with EPS after Bonferoni correction. Our findings suggest that the 5′-regulatory region of SLC6A3 plays an important role in response to clozapine and that its role in EPS needs to be replicated in a large-scale well designed study. 相似文献
4.
Lucas A. de Azeredo Diego L. Rovaris Nina R. Mota Evelise R. Polina Francine Z. Marques Verônica Contini Eduardo S. Vitola Paulo Belmonte-de-Abreu Luis A. Rohde Eugenio H. Grevet Claiton H. D. Bau 《European archives of psychiatry and clinical neuroscience》2014,264(5):401-408
The dopamine transporter (SLC6A3/DAT1) plays a key role in the regulation of dopaminergic neurotransmission and is the major site of action for methylphenidate, a first-line medication for attention deficit hyperactivity disorder (ADHD). Most genetic association studies with ADHD have investigated a 40-bp variable number of tandem repeats (VNTR) polymorphism in the 3′-untranslated region (UTR) of the DAT1, but these investigations have reported heterogeneous findings. The few studies focused on the 5′ region have reported promising results. Despite rs2652511 not being included, nor having any proxy SNP available in GWAS, the few candidate gene studies that analyzed it suggested an association with ADHD and schizophrenia. Here, we analyzed the ?839 C/T (rs2652511) promoter variant and the 3′-UTR and intron 8 (Int8) VNTR polymorphisms in 522 adults with ADHD and 628 blood donor controls. The diagnostic procedures followed the DSM-IV criteria. A significant association was detected (P = 0.002) between the rs2652511 C-allele with ADHD. In addition, the 6-repeat allele of Int8 VNTR was associated with higher inattention scores (P = 0.034). The haplotype analysis including DAT1 3′-UTR and Int8 VNTR polymorphisms did not reveal associations with ADHD susceptibility or severity dimensions. These findings extend to adult samples previous findings from children samples on the role of the rs2652511 polymorphism in the promoter region of DAT1 as a risk factor for ADHD susceptibility. 相似文献
5.
Katja Zerjavic Boris Zagradisnik Lidija Lokar Marjana G. Krasevac Nadja K. Vokac 《Thrombosis research》2013
Background
The inherited JAK2 46/1 haplotype is strongly associated with the development of myeloproliferative neoplasms (MPNs), and its increased frequency has also been reported in splanchnic venous thrombosis (SVT). In the present study, the role of the JAK2 46/1 haplotype in non-splanchnic venous thrombosis (non-SVT) was investigated.Methods and Results
We genotyped 438 patients with non-SVT, 226 patients with MPNs and 459 healthy controls for three single nucleotide polymorphisms (SNPs) which tag the JAK2 46/1 haplotype (rs12342421 G > C, rs12343867 T > C and rs10974944 C > G). We found statistically significant association of the rs12342421 GC + CC genotypes (OR = 1.40; p = 0.023) and the rs12343867 TC + CC genotypes (OR = 1.83; p = 7.02x10- 5) with non-SVT. We also found that the CC haplotype of these two SNPs was associated with an increased risk of the disease (OR = 1.68; p = 0.009). Stratification analysis indicated that the observed association of the JAK2 46/1 haplotype with non-SVT was probably largely free of confounding effect of thrombophilic risk factors. In addition, we established a strong association of SNPs rs12342421 and rs10974944 and their CG haplotype with MPNs and with JAK2 V617F-positive MPNs.Conclusions
This study provides statistical evidence that SNPs rs12342421 and rs12343867 are associated with an increased risk of non-SVT. Consistently, haplotypes of the SNPs were also associated with non-SVT risk, suggesting that inherited genetic variation in the JAK2 gene may play a role in the pathogenesis of non-SVT. Furthermore, the reported associations of the JAK2 46/1 haplotype with MPNs as well as with the occurrence of the JAK2 V617F mutation in MPNs were confirmed. 相似文献6.
Chien YL Wu YY Chiu YN Liu SK Tsai WC Lin PI Chen CH Gau SS Chien WH 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(6):1512-1517
Autism is a complex neurodevelopmental disorder with high heritability. Despite different approaches worldwide to identify susceptibility loci or genes for autism spectrum disorders (ASDs), no consistent result has been reported. CNS patterning genes have been recognized as candidate genes for autism based on neuroimage and neuropathology evidence. This study investigated four candidate genes (WNT2, EN2, SHANK3, and FOXP2) by a tag SNP approach in a family-based association study. The trio samples include 1164 subjects from 393 families, including 393 probands (aged 9.1 ± 4.0 years; male, 88.6%) diagnosed with autistic disorder (n = 373) or Asperger's disorder (n = 20) according to the DSM-IV diagnostic criteria and confirmed by the Chinese ADI-R interview. Three tag SNPs of EN2 (7q36), 6 SNPs of WNT2 (7q31-33), 5 SNPs of SHANK3 (22q13.3), 3 SNPs of FOXP2 (7q31) were genotyped. TDT analysis was done to test the association of each tag SNP and haplotype. There was no association with autism for 17 tag SNPs of WNT2, EN2, SHANK3, and FOXP2 based on SNP analyses. Haplotype analyses did not reveal significant association except for the 6 tag SNPs of WNT2 gene showing a significant association on one haplotype composed of rs2896218 and rs6950765 (G-G) (p = 0.0095). Other haplotypes composed of rs2896218 and rs6950765 (G-G) were also significantly associated with autism. The present study indicates that SHANK3 may not be a critical gene for the etiology of ASDs in Han Chinese population. Inconsistent findings in EN2 and FOXP2 in the Han Chinese population need further clarification. A haplotype of WNT2 (rs2896218-rs6950765: G-G) is significantly associated with ASDs in our trios samples, this finding warrants further validation by different sample and confirmation by functional study. 相似文献
7.
Michael J. Lucht Sven Barnow Christine Sonnenfeld Albert Rosenberger Hans Joergen Grabe Winnie Schroeder Henry Völzke Harald J. Freyberger Falko H. Herrmann Heyo Kroemer Dieter Rosskopf 《Progress in neuro-psychopharmacology & biological psychiatry》2009
Associations of oxytocin receptor gene (OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin OXTR rs53576 A/A genotype showed lower positive affect scores (F = 5.532, df = 1; p = 0.019). This effect was restricted to males (F = 13.098, df = 1; p = 0.00047). Haplotypes constructed with the three markers were associated with positive affect (p = 0.0012), negative affect (p < 0.0001) and emotional loneliness (p < 0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (T = 2.247, p = 0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ. 相似文献
8.
J. Park M. Willmott G. Vetuz C. Toye A. Kirley Z. Hawi K.J. Brookes M. Gill L. Kent 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Some children with ADHD also have social and communication difficulties similar to those seen in children with autistic spectrum disorders and this may be due to shared genetic liability. As the oxytocin receptor (OXTR) gene has been implicated in social cognition and autistic spectrum disorders, this study investigated whether OXTR polymorphisms previously implicated in autism were associated with ADHD and whether they influenced OXTR mRNA expression in 27 normal human amygdala brain samples. The family-based association sample consisted of 450 DSM-IV diagnosed ADHD probands and their parents. Although there was no association with the ADHD phenotype, an association with social cognitive impairments in a subset of the ADHD probands (N = 112) was found for SNP rs53576 (F = 5.24, p = 0.007) with post-hoc tests demonstrating that the AA genotype was associated with better social ability compared to the AG genotype. Additionally, significant association was also found for rs13316193 (F = 3.09, p = 0.05) with post-hoc tests demonstrating that the CC genotype was significantly associated with poorer social ability than the TT genotype. No significant association between genotype and OXTR mRNA expression was found. This study supports previous evidence that the OXTR gene is implicated in social cognition. 相似文献
9.
Yilmaz Z Kaplan AS Zai CC Levitan RD Kennedy JL 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(4):948-952
Up to one third of patients with bulimia nervosa (BN) report a history of ADHD symptoms, and both disorders may also be associated with dopaminergic abnormalities. COMT gene, coding for an enzyme responsible for the degradation of dopamine, may play a part in the etiology of ADHD and BN. This study aimed to (1) examine if certain variants of the COMT genetic markers (rs6269, rs4633, rs4818 and rs4680) are more common in BN versus controls; (2) assess transmission of COMT alleles in BN families; and (3) explore the role of COMT genotypes and haplotypes in bulimic women with childhood ADHD history. 72 BN probands and unaffected relatives were genotyped for COMT rs4680 (Val158Met) and three adjacent markers. The remaining 165 probands were matched with nonpsychiatric controls. We also investigated if COMT variants and haplotypes were associated with childhood ADHD history in a subgroup of 86 BN probands who completed the Wender Utah Rating Scale (WURS). Our results showed that cases and controls did not differ in COMT allele and haplotype frequencies. In contrast, specific alleles of all four COMT markers and the medium-activity haplotype were preferentially transmitted to the offspring with BN. COMT Val158 allele was overrepresented and the medium-activity haplotype was underrepresented in BN with childhood ADHD history (p = 0.010). These findings suggest a possible role for COMT variants and related haplotypes in BN and its subphenotypes. If replicated, these preliminary findings may have implications for the prevention and treatment of BN that emerges in the context of childhood ADHD. 相似文献
10.
Yuko Okahisa Hiroshi Ujike Hiroshi Kunugi Takeshi Ishihara Masafumi Kodama Manabu Takaki Tatsuya Kotaka Shigetoshi Kuroda 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Leukemia inhibitory factor (LIF), a member of the interleukin-6 cytokine family, regulates the neuronal phenotype and coordinates astrocyte, oligodendrocyte, microglia, and inflammatory cell responses. The LIF gene is located on 22q12.1–q12.2, a hot spot for schizophrenia. Three polymorphisms of the LIF gene (rs929271, rs737812, and rs929273) were examined in a case–control association study of 390 patients with schizophrenia and 410 age- and sex-matched controls. Effects of a risk genotype of LIF on cognitive domains were evaluated by the Wechsler Adult Intelligence Scale—Revised, Wechsler Memory Scale—Revised, and Wisconsin Card Sorting Test (WCST) in 355 healthy volunteers. The LIF gene showed significant associations with schizophrenia at rs929271 and a haplotype consisting of rs929271–rs737812. After stratification by subtype of schizophrenia, the hebephrenic, but not paranoid, type was associated with the LIF gene at rs929271 (allele, P = 0.014) and the haplotype (permutation P = 0.013). Having the T-allele and T-carrier genotypes (TT and TG) of rs929271 were risks for hebephrenic schizophrenia, and the odds ratios were 1.38 (95% CI: 1.21–1.56) and 1.54 (95%CI: 1.19–1.98), respectively. Subjects with T-carrier genotypes made significantly more errors on the WCST compared with those without (P = 0.04). The present study indicated that the LIF gene variant may produce susceptibility to hebephrenic schizophrenia and deterioration of working memory function. 相似文献
11.
Liu J Li J Li T Wang T Li Y Zeng Z Li Z Chen P Hu Z Zheng L Ji J Lin H Feng G Shi Y 《Brain, behavior, and immunity》2011,25(3):429-433
Previous studies have reported that the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, which is related to immunological function such as T-cell regulation, is associated with psychiatric disorders. In this study, we studied the relationship between CTLA-4 and three major psychiatric disorders, schizophrenia, major depressive disorder and bipolar disorder in the Chinese Han population. We recruited 1140 schizophrenia patients, 1140 major depressive disorder patients, 1140 bipolar disorder patients, and 1140 normal controls to examine the risk conferred by 6 tag SNPs (rs231777, rs231775, rs231779, rs3087243, rs5742909, rs16840252) in the CTLA-4 gene. We found that rs231779 conferred a risk for schizophrenia (Pallele = 0.0003, Pgenotype = 0.0016), major depressive disorder (Pallele = 0.0006, Pgenotype = 0.0026) and bipolar disorder (Pallele = 0.0004, Pgenotype = 0.0018). In addition, rs231777 and rs16840252 had a significant association with schizophrenia (rs231777: Pallele = 0.0201, rs16840252: Pallele = 0.0081, Pgenotype = 0.0117), and rs231777 had significant association with bipolar disorder (rs231777: Pallele = 0.0199). However, after 10,000 permutations, only rs231779 remained significant (schizophrenia: Pallele = 0.0010, Pgenotype = 0.0145, major depressive disorder: Pallele = 0.0010, Pgenotype = 0.0201, bipolar disorder: Pallele = 0.0008, Pgenotype = 0.0125). Our results suggest that shared common risk factors for schizophrenia, major depressive disorder and bipolar disorder exist in the CTLA-4 gene in the Chinese Han population. 相似文献
12.
B.G. Schimmelmann S. Friedel T.T. Nguyen C.I. Ganz Vogel C. Wilhelm T.J. Renner H. Palmason S. Walitza C. Freitag M. Linder A. Warnke B. Herpertz-Dahlman J. Hebebrand 《Journal of psychiatric research》2009,43(10):941-945
Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder of childhood onset. Clinical and biological evidence points to shared common central nervous system (CNS) pathology of ADHD and restless legs syndrome (RLS). It was hypothesized that variants previously found to be associated with RLS in two large genome-wide association studies (GWA), will also be associated with ADHD.SNPs located in MEIS1 (rs2300478), BTBD9 (rs9296249, rs3923809, rs6923737), and MAP2K5 (rs12593813, rs4489954) as well as three SNPs tagging the identified haplotype in MEIS1 (rs6710341, rs12469063, rs4544423) were genotyped in a well characterized German sample of 224 families comprising one or more affected sibs (386 children) and both parents.We found no evidence for preferential transmission of the hypothesized variants to ADHD. Subsequent analyses elicited nominal significant association with haplotypes consisting of the three SNPs in BTBD9 (χ2 = 14.8, df = 7, nominal p = 0.039). According to exploratory post hoc analyses, the major contribution to this finding came from the A-A-A-haplotype with a haplotype-wise nominal p-value of 0.009. However, this result did not withstand correction for multiple testing.In view of our results, RLS risk alleles may have a lower effect on ADHD than on RLS or may not be involved in ADHD. The negative findings may additionally result from genetic heterogeneity of ADHD, i.e. risk alleles for RLS may only be relevant for certain subtypes of ADHD. Genes relevant to RLS remain interesting candidates for ADHD; particularly BTBD9 needs further study, as it has been related to iron storage, a potential pathophysiological link between RLS and certain subtypes of ADHD. 相似文献
13.
14.
《Research in developmental disabilities》2014,35(7):1658-1665
The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3′-UTR 9/10 VNTR, rs27072 in the 3′-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents’ ratings) was associated with DAT1 intron8 (ηp2 = .063) and rs2283265 (ηp2 = .044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (ηp2 = .065) and depression (ηp2 = .059), and for DRD2 rs2283265, depression (ηp2 = .053). DRD2 rs2283265 was associated with teachers’ global ratings of ADHD (ηp2 = .052). DAT1 intron8 was associated with parent-rated hyperactivity (ηp2 = .045) and both DAT1 9/10 VNTR (ηp2 = .105) and DRD2 rs2283265 (ηp2 = .069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples. 相似文献
15.
Soo-Churl Cho Hyo-Won Kim Boong-Nyun Kim Jae-Won Kim Min-Sup Shin Dae-Yeon Cho Seockhoon Chung Sun-Woo Jung Hee Jeong Yoo In-Won Chung Un-Sun Chung Jung-Woo Son 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Objective
Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Neurotrophin-3 (NTF3), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, has been identified as a factor in the development of ADHD. We investigated the relationships between ADHD and NTF3 gene polymorphism.Methods
We conducted a case–control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 151 trios, and compared the intelligence quotient (IQ) and a continuous performance test (CPT) according to the genotype of two single-nucleotide polymorphisms (SNPs) (rs6332 and rs6489630) in the NTF3 gene.Results
In the case–control and family-based analyses, NTF3 was not significantly associated with ADHD. However, in the ADHD probands, the subjects with AA genotype in the rs6332 SNP had significantly higher mean T-scores for commission errors on the CPT than did those with the AG genotypes (p = 0.045). The mean IQ of the ADHD probands who had the CC genotype of the rs6489630 SNP were higher compared with those who had the CT or TT genotype (p = 0.035). The mean T-score for response time on the CPT was higher in the subjects with TT genotype in the rs6489630 SNP compared to those with the CC or CT genotype, even after adjusting for the effect of IQ (p = 0.021).Conclusions
These results provide preliminary evidence of an association between NTF3 and the intelligence and selective attention deficit in the Korean population. 相似文献16.
Otowa T Kawamura Y Sugaya N Yoshida E Shimada T Liu X Tochigi M Umekage T Miyagawa T Nishida N Kaiya H Okazaki Y Tokunaga K Sasaki T 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(2):545-549
Background
Panic disorder (PD) is a severe and chronic psychiatric disorder with genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B) gene has been reported to be associated with several psychiatric disorders. Several studies indicated that PDE4B may be involved in the regulation of anxiety and depression. Therefore, we investigate the association of PDE4B with PD in the Japanese population.Methods
We genotyped 14 single nucleotide polymorphisms (SNPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162 males and 245 females). Differences in the genotype, allele and haplotype frequencies between the two groups were compared.Results
We found a significant association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A, permutation P = 0.031, OR = 1.81, 95% CI = 1.30-2.51). Sex-specific analyses demonstrated that PDE4B was associated with PD in females in the allele/genotype and haplotype analyses (rs10454453, allele P = 0.042, genotype P = 0.0034; haplotype C-T-T-A, permutation P = 0.028).Conclusion
Our results suggest that PDE4B may play a role in the pathophysiology of PD in the Japanese population. Replication studies using larger samples will be needed for more reliable conclusions. 相似文献17.
Pan Y Wang KS Aragam N 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(1):154-160
Family, twin, and adoption studies have indicated that human intelligence quotient (IQ) has significant genetic components. We performed a low-density genome-wide association analysis with a family-based association test to identify genetic variants influencing IQ, as measured by Wechsler Adult Intelligence Scale full-score IQ (FSIQ). We examined 11,120 single-nucleotide polymorphisms (SNPs) from the Affymetrix GeneChips 10K mapping array genotyped in 292 nuclear families from Genetic Analysis Workshop 14, a subset from the Collaborative Study on the Genetics of Alcoholism (COGA). A replication analysis was performed using part of International Multi-Center ADHD Genetics Project (IMAGE) dataset. Twenty-two SNPs were identified as having suggestive associations with IQ (p < 10− 3) in the COGA sample and eleven of the SNPs were located within known genes. In particular, NTM at 11q25 (rs411280, p = 0.000764) and NR3C2 at 4q31.1 (rs3846329, p = 0.000675) were two novel genes which have not been associated with IQ in other studies. It has been reported that NTM might play a role in late-onset Alzheimer disease while NR3C2 may be associated with cognitive function and major depression. The associations of these two genes were well-replicated by single-marker and haplotype analyses in the IMAGE sample. In conclusion, our findings provide evidence that chromosome regions of 11q25 and 4q31.1 contain genes affecting IQ. This study will serve as a resource for replication in other populations. 相似文献
18.
Li W Song X Zhang H Yang Y Jiang C Xiao B Li W Yang G Zhao J Guo W Lv L 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(6):1505-1511
Schizophrenia (SZ) is a common and complex psychiatric disorder with a strong genetic component. Previous research suggests that mutations altering genes in neurodevelopmental pathways contribute to SZ. Reelin gene (RELN) maps to chromosome 7q22.1, the encoded protein plays a pivotal role in guiding neuronal migration, lamination and connection during embryonic brain development. Several reports had indicated that reduced RELN expression is associated with human mental illnesses such as SZ, mood disorders and autism. In this study, case-control association analyses were performed in the Han Chinese population to determine if the RELN gene is a susceptibility gene for SZ. Thirty-seven single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was found between rs12705169 and SZ (p = 0.001). Moreover, the haplotypes constructed from five SNPs showed significant differences between cases and controls (p = 0.041). When subjects were divided by gender, rs12705169 remained significant difference only in females (OR = 0.24, 95%CI = 0.14-0.40 for CC and OR = 0.40, 95%CI = 0.27-0.58 for AC), both in the allele and genotype (p = 0.0001 for both). This study describes a positive association between RELN and SZ in the Han Chinese population, and provides genetic evidence to support the gender difference of SZ. 相似文献
19.
Kati Koido Triin Eller Sulev Kõks Tanel Traks Jakov Shlik Eero Vasar Eduard Maron 《Journal of psychiatric research》2010,44(5):275-277
Genetic regulation of immune system and inflammatory response may be related to the pathogenesis and manifestations of mood and anxiety disorders. In the present study we examined a range of single-nucleotide polymorphisms (SNP) in chromosomal region 1q32, the locus of interleukin 10 (IL10) gene, in patients with major depressive disorder (n = 312) and panic disorder (n = 210), and matched healthy controls (n = 356). We found no significant associations of the SNPs in IL10 family genes with either diagnostic group. Haplotype analysis revealed seven haplotype blocks, but their frequencies did not differ between patients and controls. Significant associations were detected for SNP rs1539243 in IKBKE (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon) gene showing different allelic and genotypic distributions in the total as well as in separate diagnostic groups as compared to controls. IKBKE emerged as a candidate for further studies of genetic factors associated with panic disorder and major depressive disorder. 相似文献
20.
Caroline Dubertret Claire Bardel Nicolas Ramoz Pierre-Marie Martin Jean-Charles Deybach Jean Adès Philip Gorwood Laurent Gouya 《Progress in neuro-psychopharmacology & biological psychiatry》2010