Different physiological properties in a pool of mandibular closer motor neurons in a caterpillar, Bombyx mori

The zinc finger and DHHC domain-containing protein 8 (ZDHHC8) gene is located on chromosome 22q11, which several genome scans have provided repeated evidence for a significant linkage with bipolar disorder (BPD) and schizophrenia. A recent study revealed that a single nucleotide polymorphism (SNP), rs175174, which has potential effects on splicing, in intron 4 of the ZDHHC8 gene is associated with susceptibility to patients with schizophrenia in US and South Africa. We examined three SNPs of the ZDHHC8 gene, including rs175174, by case–control association in Japanese patients with BPD (N = 172) and controls (N = 298) or patients with schizophrenia (N = 407) and controls (N = 497). No significant association with BPD or schizophrenia was observed. After stratification by subcategories, bipolar I and II of BPD, and paranoid and disorganized types of schizophrenia, no significant association was found, nor was a significant association with either disorder found after dividing by gender. These data suggest that the ZDHHC8 gene may not be associated with susceptibility to BPD or schizophrenia, at least in a Japanese population.     

Effect of 5-haplotype of dysbindin gene (DTNBP1) polymorphisms for the susceptibility to bipolar I disorder.

We investigated a possible association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). Five SNPs within DTNBP1 (rs3213207, rs1011313, rs2005976, rs760761, and rs2619522) were genotyped for 151 patients with BID and 478 controls. We observed a significant protective association of the haplotype A-C-G-T-A (all SNPs, P = 0.00016) and particularly G-T-A (the last three SNP, P = 0.00007) within DTNBP1 variants investigated. Single marker and subgroup (e.g., psychotic features, age at onset, family history, etc.) analyses showed no significant association. Although the association was due to a small number of subjects, specific DTNBP1 haplotypes, previously associated with schizophrenia, may be also associated with BID. Adequately powered studies from different ethnicities will be necessary to confirm our findings.     

Alternative splicing of the mouse embryonic poly(A) binding protein (Epab) mRNA is regulated by an exonic splicing enhancer: a model for post-transcriptional control of gene expression in the oocyte

Embryonic poly(A) binding protein (EPAB), expressed in oocytes and early embryos, binds and stabilizes maternal mRNAs, and mediates initiation of their translation. We identified an alternatively spliced form of Epab lacking exon 10 (c.Ex10del) and investigated the regulation of Epab mRNA alternative splicing as a model for alternative splicing in oocytes and early preimplantation embryos. Specifically, we evaluated the following mechanisms: imprinting; RNA editing and exonic splicing enhancers (ESEs). Sequence analysis led to the identification of two single nucleotide polymorphisms (SNPs): one was detected in exon 9 (rs55858A/G), and served as a marker for the parental origin of the alternatively spliced form, and the other was found in exon 10 (rs56574G/C), and co-segregated with the exon 9 SNP. We found that the presence of rs56574G in exon 10 led to the formation of an ESE, leading to efficient exclusion of exon 10. Real-time RT-PCR results revealed a 5-fold increase in the expression of the c.Ex10del alternative splicing variant in animals carrying rs56574G/G in exon 10 compared with rs56574C/C at the same locus. Our findings suggest that SNPs may alter the ratio between alternative splicing variants of oocyte-specific proteins. The role that these subtle differences play in determining individual reproductive outcome remains to be determined.     

Association of polymorphisms in the haplotype block spanning the alternatively spliced exons of the NTNG1 gene at 1p13.3 with schizophrenia in Japanese populations

Chromosome 1p13 is linked with schizophrenia in Japanese families, and one of the candidate genes in this region is the netrin G1 (NTNG1) gene at 1p13.3. Associations of 56 tag single-nucleotide polymorphisms (SNPs) with schizophrenia were explored by transmission disequilibrium analysis in 160 Japanese trios and by case-control analysis in 2,174 Japanese cases and 2,054 Japanese controls. An association between SNP rs628117 and schizophrenia was identified by case-control comparison (nominal allelic p=0.0009; corrected p=0.006). The associated polymorphism is located in intron 9 and in the haplotype block encompassing the alternatively spliced exons of the gene. Allelic association of a different SNP in the same haplotype block in Japanese families was previously reported. These findings support that the NTNG1 gene is associated with schizophrenia in the Japanese.     

Tests of linkage and allelic association between markers in the 1p36 PRKCZ (protein kinase C zeta) gene region and bipolar affective disorder

Three linkage studies of families with multiple cases of bipolar disorder and/or unipolar affective disorder have confirmed the involvement of the chromosome 1p36 region in the etiology of affective disorders with LOD scores of 2.7, 3.6, and 3.97. We investigated the protein kinase C zeta gene (PRKCZ) as a susceptibility locus for bipolar disorder because it is highly brain expressed and is localized close to the marker D1S243 which was linked to affective disorder in a single large UCL bipolar disorder family with a LOD of 3.1. PRKCZ encodes an unusual type of protein kinase which affects axonal differentiation through Wnt-signaling. We genotyped four microsatellite markers and nine single nucleotide polymorphism (SNP) markers within or near the PRKCZ gene in the UCL case-control sample of 600 bipolar disorder patients and up to 605 supernormal controls. Markers D1S243 and rs3128396 were significantly associated with bipolar disorder (empirical P = 0.037 and P = 0.040, respectively). We also included data from eight SNPs which were genotyped as part of our GWA study on bipolar disorder for association analysis. Tests of haplotypic association found that a haplotype block comprising markers rs3128296, rs2503706, and rs3128309 was associated with bipolar disorder (empirical P = 0.004). A previous linkage study had shown greater evidence for linkage within female cases compared to males. Therefore, to assess if the association was sex-specific, we performed a female-only allelic-association analysis, which resulted in SNPs rs3128296 and rs3128309 becoming associated with bipolar disorder (P = 0.004 and P = 0.016, respectively). PRKCZ may play a role in susceptibility to bipolar affective disorder.     

Effect of DISC1 SNPs on brain structure in healthy controls and patients with a history of psychosis

Disrupted-in-Schizophrenia-1 (DISC1) has been suggested as a susceptibility locus for a broad spectrum of psychiatric disorders. Risk variants have been associated with brain structural changes, which overlap alterations reported in schizophrenia and bipolar disorder patients. We used genome-wide genotyping data for a Norwegian sample of healthy controls (n?=?171) and patients with a history of psychosis (n?=?184), to investigate 61 SNPs in the DISC1 region for putative association with structural magnetic resonance imaging (sMRI) measures (hippocampal volume; mean cortical thickness; and total surface area, as well as cortical thickness and area divided into four lobar measures). SNP rs821589 was associated with mean temporal and total brain cortical thickness in controls (P(adjusted) =?0.009 and 0.02, respectively), but not in patients. SNPs rs11122319 and rs1417584 were associated with mean temporal cortical thickness in patients (P(adjusted) =?0.04 and 0.03, respectively), but not in controls, and both SNPs have previously been highly associated with DISC1 gene expression. There were significant genotype?× case-control interactions. There was no significant association between SNPs and cortical area or hippocampal volume in controls, or with any of the structural measures in cases, after correction for multiple comparisons. In conclusion, DISC1 SNPs might impact brain structural variation, possibly differently in psychosis patients versus controls, but independent replication will be needed to confirm our findings. ? 2012 Wiley Periodicals, Inc.     

Sequencing of the ANKYRIN 3 gene (ANK3) encoding ankyrin G in bipolar disorder reveals a non-conservative amino acid change in a short isoform of ankyrin G

Significant association between polymorphisms at the ANK3 gene with bipolar disorder has previously been reported and confirmed in several samples. Here we report on association between ANK3 and bipolar disorder in a new sample of 593 patients and 642 controls (UCL2) as well as the results of sequencing of the exons and flanking regions of ANK3 from bipolar patients. Single nucleotide polymorphisms (SNPs) associated with bipolar disorder in our original GWA study (UCL1) were genotyped and tested for association in the new sample. Novel SNPs found by sequencing were genotyped in both samples to test for association with bipolar disorder. None of the SNPs previously associated with bipolar disorder were associated in the UCL2 sample. One of the four SNPs associated in the UCL1 sample, rs1938526, was still significantly associated with bipolar disorder when the UCL1 and UCL2 samples were combined (P?=?0.0095). The results demonstrate the impact of heterogeneity on replication of allelic associations even within well-defined ancestral populations. DNA sequencing revealed a novel low frequency (0.007) ANK3 SNP (ss469104599) which causes a non-conservative amino acid change at position 794 in the shorter isoforms of the ankyrin G protein. Protein-function analysis software predicted the amino acid change to be "probably damaging" and it could therefore be detrimental to the function of this isoform. Given that there was only a modest increase in the allele frequency of ss469104599 in cases compared to controls further association studies are needed in additional samples to establish a possible etiological role for this amino acid change.     

DTNBP1基因rs4715986位点多态性与中国汉族人群偏执型精神分裂症相关

目的通过两步法研究中国汉族人群DTNBP1基因的多态性与偏执型精神分裂症的相关性。方法发现阶段:在532例偏执型精神分裂症患者及488名健康对照中使用Sanger测序方法检测DTNBP1的11个SNP位点。验证阶段:在1 111例偏执型精神分裂症患者及1 435名健康对照中使用Taqman探针分型的方法对发现阶段检出阳性的rs4715986位点进行验证。结果发现DTNBP1中的rs4715986位点与偏执型精神分裂症的高患病风险相关(χ~2=11.02,P0.01)。在验证人群中重复出rs4715986与偏执型精神分裂症的相关性(χ~2=9.29,P=0.01)。结论DTNBP1基因rs4715986位点的多态性与偏执型精神分裂症的高患病风险相关。DTNBP1可能是中国汉族人群偏执型精神分裂症的易感基因。     

No association of two common SNPs at position -1727 A/T, -50 C/T of GSK-3 beta polymorphisms with schizophrenia and bipolar disorder of Korean population

Recent studies have suggested the involvement of Glycogen synthase kinase-3 beta (GSK-3 beta) in pathogenesis and treatment target of schizophrenia and bipolar disorder, which led to consider GSK-3 beta as one of the candidate genes for those disorders. However, the association analysis between GSK-3 beta and either schizophrenia or bipolar disorder is yet to be reported in Korean population. Along with 350 healthy individuals, a sample of 138 schizophrenia and 120 bipolar patients was analyzed for two common SNPs at position -1727 A/T and -50 C/T polymorphism localized in intron 1 of the gene. The results showed that allele, genotype and haplotype distributions for the two SNPs do not differ between the controls and neither schizophrenia nor bipolar disorder patients. We also analyzed the association between the controls and the combined samples of schizophrenia and bipolar disorder, but no association was found. In conclusion, these results suggest that the GSK-3 beta is not associated with the development of schizophrenia and bipolar disorder in Korean population.     

Supportive evidence for neuregulin 1 as a susceptibility gene for schizophrenia in a Japanese population

Schizophrenia is a complex genetic disorder and affects approximately 1% of the population worldwide. Recently, Stefansson et al. identified neuregulin 1 (NRG1) on 8p12 as a susceptibility gene for schizophrenia in the Icelandic population. It was reported that the at-risk haplotype (“Hapice”) constructed from five SNPs and two microsatellite markers was found to be over-represented in patients with schizophrenia compared to controls. Since then several independent studies have supported the association of NRG1 with schizophrenia. We performed a case–control association study using the four SNPs in a Japanese sample. We genotyped three SNPs (SNP8NRG221533, SNP8NRG241930, and SNP8NRG243177) from Stefansson et al. and one SNP (rs1081062) located in intron 1 of NRG1. There were no significant differences in allele frequencies for each SNP between cases and controls, however, homozygotes of minor alleles in SNP8NRG241930, SNP8NRG243177, and rs1081062 were associated with an increased risk of schizophrenia (P = 0.025, OR = 4.14; P = 0.041, OR = 1.43; and P = 0.0023, OR = 3.06, respectively). Furthermore, the haplotype constructed from four SNPs shows a significant association with schizophrenia (permutation P = 0.026). Our data support the hypothesis that NRG1 gene is a susceptibility gene for schizophrenia.     

儿茶酚-O-甲基转移酶基因单核苷酸多态性位点与精神分裂症的关联研究

目的 探讨儿茶酚-O-甲基转移酶(catechol-O-methyl transferanse,COMT)基因8个单核苷酸多态性位点(single nRcleotide polymorphism,SNP)与粤东潮汕地区精神分裂症的关系.方法 应用聚合酶链式反应-聚丙烯酰胺凝胶芯片技术检测COMf基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)在粤东潮汕地区的279例精神分裂症患者和100名健康对照中的分布,并借助于plink软件对所得数据进行关联分析.结果 单个位点等位基因频率在两组间的分布差异无统计学意义;单倍型(G)-G-A-A[(rs4680)-rsl65599-rs2075507-rs6269]和单倍型A-A-C-(G)[rs2075507-rs6269-rs4633-(rs6267)]频率两组分布差异有统计学意义,精神分裂症组低于正常对照组,提示它们可能是精神分裂症的保护因素.结论 在中国粤东地区汉族人群中,COMT基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)与精神分裂症无关联性,其中的两个单倍型可能是精神分裂症的保护因素.但本研究不能排除COMT基因可能存在其他功能性变异位点与精神分裂症相关.     

Polymorphisms in the vitamin D receptor and their associations with risk of schizophrenia and selected anthropometric measures.

The association between vitamin D levels and skeletal growth has long been recognized. However, exposure to low levels of vitamin D during early life is also known to alter brain development, and is a candidate risk factor for schizophrenia. This study examines the association between four polymorphisms in the vitamin D receptor (VDR) and 1) risk of schizophrenia, and 2) three anthropometric variables (height, head size, and head shape). Four single-nucleotide polymorphisms (SNPs; rs10735810/FokI, rs1544410/BsmI, rs7975232/ApaI, and rs731236/TaqI) in the VDR gene were genotyped in 179 individuals with schizophrenia and 189 healthy controls. No significant associations were detected between any of the four VDR SNPs and risk of schizophrenia. Patients were slightly but significantly shorter compared to controls. Of the four SNPs, only rs10735810/FokI was associated with any of the anthropometric measures: the M4 isoform of this SNP was significantly associated with larger head size (P = 0.002). In light of the evidence demonstrating a role for vitamin D during brain development, the association between polymorphisms in VDR and brain development warrants closer scrutiny.     

儿茶酚-O-甲基转移酶基因单核苷酸多态性位点与精神分裂症的关联研究

目的 探讨儿茶酚-O-甲基转移酶(catechol-O-methyl transferanse,COMT)基因8个单核苷酸多态性位点(single nRcleotide polymorphism,SNP)与粤东潮汕地区精神分裂症的关系.方法 应用聚合酶链式反应-聚丙烯酰胺凝胶芯片技术检测COMf基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)在粤东潮汕地区的279例精神分裂症患者和100名健康对照中的分布,并借助于plink软件对所得数据进行关联分析.结果 单个位点等位基因频率在两组间的分布差异无统计学意义;单倍型(G)-G-A-A[(rs4680)-rsl65599-rs2075507-rs6269]和单倍型A-A-C-(G)[rs2075507-rs6269-rs4633-(rs6267)]频率两组分布差异有统计学意义,精神分裂症组低于正常对照组,提示它们可能是精神分裂症的保护因素.结论 在中国粤东地区汉族人群中,COMT基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)与精神分裂症无关联性,其中的两个单倍型可能是精神分裂症的保护因素.但本研究不能排除COMT基因可能存在其他功能性变异位点与精神分裂症相关.     

儿茶酚-O-甲基转移酶基因单核苷酸多态性位点与精神分裂症的关联研究

目的 探讨儿茶酚-O-甲基转移酶(catechol-O-methyl transferanse,COMT)基因8个单核苷酸多态性位点(single nRcleotide polymorphism,SNP)与粤东潮汕地区精神分裂症的关系.方法 应用聚合酶链式反应-聚丙烯酰胺凝胶芯片技术检测COMf基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)在粤东潮汕地区的279例精神分裂症患者和100名健康对照中的分布,并借助于plink软件对所得数据进行关联分析.结果 单个位点等位基因频率在两组间的分布差异无统计学意义;单倍型(G)-G-A-A[(rs4680)-rsl65599-rs2075507-rs6269]和单倍型A-A-C-(G)[rs2075507-rs6269-rs4633-(rs6267)]频率两组分布差异有统计学意义,精神分裂症组低于正常对照组,提示它们可能是精神分裂症的保护因素.结论 在中国粤东地区汉族人群中,COMT基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)与精神分裂症无关联性,其中的两个单倍型可能是精神分裂症的保护因素.但本研究不能排除COMT基因可能存在其他功能性变异位点与精神分裂症相关.

Abstract：

Objective To investigate the association between 8 polymorphisms in the catechol-O-methyl transferase gene (COMT) and schizophrenia in Yuedong-Chaoshan region of China. Methods Eight single nucleotide polymorphism (SNPs), namely rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267,rs6269 and rs4633, in the COMT gene were genotyped in 279 schizophrenia patients and 100 healthy controls. Results There was no significant difference between any single SNP and schizophrenia.However, association might exist between haplotypes (G)-G-A-A [(rs4680) -rs165599-rs2075507-rs6269]and A-A-C-(G) [rs2075507-rs6269-rs4633-(rs6267)] and schizophrenia. Conclusion In the population of Yuedong region of China, the eight SNPs (rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267,rs6269 and rs4633) in the COMT gene are unlikely to play a major role in the susceptibility to schizophrenia.There might be protective haplotypes in the COMT gene against schizophrenia.     

Dysbindin gene variants are associated with bipolar I disorder in a Korean population

The dysbindin gene (DTNBP1) has been associated with schizophrenia in several populations. Because the clinical characteristics of schizophrenia and bipolar disorder overlap in many respects and findings from genetic studies have suggested common genes between them, we conducted a case control association study of bipolar disorder in Korea to investigate the genetic association between DTNBP1 and bipolar disorder. In total, 163 patients with bipolar disorder and 350 controls were evaluated. We genotyped three single nucleotide polymorphisms of DTNBP1 (SNP A, P1763, and P1320) and analyzed the allele, genotype, and haplotype associations with bipolar disorder. We found significant genotypic associations with P1763 and P1320, but no association with SNP A in the bipolar I group. When we included bipolar II and schizoaffective disorder in the affected phenotype, the significance decreased. A positive association was observed between the SNP A-P1763 haplotype and the bipolar I phenotype. This haplotype association was lost when we either broadened our phenotype or included P1320 in a haplotype. The positive results of the present study lost significance after a Bonferroni correction for multiple testing. These findings are consistent with previous findings that showed a positive association of DTNBP1 with bipolar disorders. Moreover, our results suggest that DTNBP1 may contribute more to bipolar I disorder than bipolar II disorder or schizoaffective disorder. Further comprehensive studies will be required to clarify these association, however, it seems likely that DTNBP1 is a susceptibility gene for bipolar disorder.     

Association of polymorphisms in P2RX7 and CaMKKb with anxiety disorders

BACKGROUND: There is considerable evidence that genetic factors play an important role in the pathophysiology of affective disorders including bipolar disorder, major depressive disorder and anxiety disorders. Long-term follow up studies as well as drug treatment studies suggest that these clinical conditions share a number of pathophysiological commonalities including genetic variables. One possible candidate region is located on chromosome 12q24.31, originated from previous linkage and association studies with bipolar disorder and unipolar depression. This region contains two candidate genes for purinergic ligand-gated ion channels, P2RX7 and P2RX4, and one gene coding for calmodulin-dependent protein kinase kinase b (CaMKKb). METHODS: In the present study, we investigated the genetic associations between 15 SNPs in the candidate genes P2RX7, P2RX4 and CaMKKb on chromosome 12q24.31 in 179 patients with anxiety disorders and syndromal panic attacks versus 462 healthy controls. RESULTS: One nominal case-control association could be detected for a SNP in the 5'UTR region of P2RX4, which did not remain significant after correction for multiple testing. We found, however, a prominent association between severity of panic- and agoraphobia symptoms and an exonic SNP (rs3817190) in the CaMKKb gene and a trend for association with an exonic SNP in P2RX7 (rs1718119) with severity scores in the panic- and agoraphobia scale. CONCLUSION: The locus 12q24.31 seems to be an important genetic region for anxiety, bipolar and unipolar disorders, suggesting a genetic overlap in the group of affective disorders. The specific contribution of the herein reported gene polymorphisms to the clinical condition is still unclear and warrants further analysis.     

Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms

Neurexins are cell adhesion molecules that help to specify and stabilize synapses and provide receptors for neuroligins, neurexophilins, dystroglycans and alpha-latrotoxins. We previously reported significant allele frequency differences for single nucleotide polymorphisms (SNPs) in the neurexin 3 (NRXN3) gene in each of two comparisons between individuals who were dependent on illegal substances and controls. We now report work clarifying details of NRXN3's gene structure and variants and documenting association of NRXN3 SNPs with alcohol dependence. We localize this association signal with the vicinity of the NRXN3 splicing site 5 (SS#5). A splicing site SNP, rs8019381, that is located 23 bp from the SS#5 exon 23 donor site displays association with P = 0.0007 (odds ratio = 2.46). Including or excluding exon 23 at SS#5 produces soluble or transmembrane NRXN3 isoforms. We thus examined expression of these NRXN3 isoforms in postmortem human cerebral cortical brain samples from individuals with varying rs8019381 genotypes. Two of the splice variants that encode transmembrane NRXN3 isoforms were expressed at significantly lower levels in individuals with the addiction-associated rs8019381 'T' allele than in CC homozygotes. Taken together with recent reports of NRXN3 association with nicotine dependence and linkage with opiate dependence, these data support roles for NRXN3 haplotypes that alter expression of specific NRXN3 isoforms in genetic vulnerabilities to dependence on a variety of addictive substances.     

Tumor suppressor gene TP53 is genetically associated with schizophrenia in the Chinese population

Schizophrenia is a debilitating mental disorder. The TP53 tumor suppressor gene, encoding a phosphoprotein, is a key element in maintaining genomic stability and cell apoptosis. Recently, reduced risk of cancer in patients of schizophrenia has been reported. Some evidence also suggests the possible implication of TP53 in neurodevelopment. In order to examine the role of the TP53 gene in the pathogenesis of schizophrenic disorders, we investigated the genetic association between a functional polymorphism rs1042522 and schizophrenia by sequencing the fragment covering 72Pro> Arg in 701 cases and 695 controls in this work. In addition, we studied two other SNPs rs2078486 and rs8064946 by allele-specific PCR in the same samples. Though rs1042522 and rs8064946 did not show positive association with schizophrenia, we did observe statistically significant differences on SNP rs2078486 (P-value = 0.029; OR = 1.21; 95% CI 1.02-1.42) and on haplotype CAC (P-value = 0.0068; OR = 1.36; 95% CI 1.09-1.70). These results demonstrated that TP53 might play a role in susceptibility to schizophrenia.     

DISC1 in adult ADHD patients: An association study in two European samples

The DISC1 gene was named after its discovery in a Scottish pedigree with schizophrenia (SCZ) patients. However, subsequent studies have shown association of DISC1 variants with a range of different neurocognitive phenotypes and psychiatric disorders, including bipolar disorder (BPD), and major depression. Attention‐deficit/hyperactivity disorder (ADHD) shares some symptoms with BPD and ADHD patients often suffer from comorbid affective disorders. We wanted to examine the role of DISC1 in ADHD, and with comorbid symptoms of mood disorders. Eleven single nucleotide polymorphisms (SNPs) previously implicated in SCZ and BPD, and a DISC1 duplication involving exon 1, were genotyped in 561 adult ADHD cases and 713 controls of Norwegian ancestry. The intronic SNP rs1538979 was associated with ADHD in the Norwegian sample [odds ratio (OR): 1.33, 95% confidence interval (CI) 1.03–1.73, P = 0.03] and replicated in a Spanish adult ADHD sample of 694 cases and 735 controls, using the tagging SNP rs11122330 (meta‐analysis: P = 0.008, OR 1.25, 95% CI 1.06–1.47). In the Norwegian ADHD sample we also observed an association between the Phe607‐variant of rs6675281 and a positive score on the Mood Disorder Questionnaire (MDQ; OR = 1.44, 95% CI 1.08–1.93, P = 0.01). To our knowledge, this is the first study to show an association between DISC1 variants and ADHD. Our study suggests that further studies are warranted to resolve if DISC1 variation is involved in several common neurodevelopmental disorders including ADHD. © 2013 Wiley Periodicals, Inc.