Psychiatric Genetics最新文献

Background: 17q12 microdeletion syndrome is a rare autosomal dominant chromosomal anomaly, caused by the deletion of a 1.4 Mb-spanning DNA sequence on the long arm of chromosome 17. Herein, we report the first bipolar disease (BPD) case with a 1.6-Mb deletion in the 17q11.2-17q12 chromosome region.

Materials and methods: Physical examination of the case was performed. Karyotype and microarray analyses were performed for the case and the parents.

Results: Physical examination revealed mild dysmorphic features such as high and forehead, full cheeks, slightly depressed nasal bridge and arched eyebrow. Chromosomal analysis of the patient revealed 46, XX, del(17)(q12) karyotype, and parents' karyotype were normal. In the microarray analysis of patient, 1.6 megabases deletion was detected in the 17q12 region [arr(hg19) 17q12 (34,611,352-36,248,918) ×1]. The microarray analysis of the mother was normal. The father's microarray showed 473 kilobases duplication in the 11p11.12 region.

Conclusion: Although 17q12 deletion syndrome has been associated with bipolar disorder, very few such cases have been described in the literature. Genetic counseling should be considered in patients with remarkable phenotype, complex symptomatology, neurodevelopmental disorder and additional conspicuous medical conditions.

An improved understanding of genetic etiological heterogeneity in a psychiatric condition may help us (a) isolate a neurophysiological 'final common pathway' by identifying its upstream genetic origins and (b) facilitate characterization of the condition's phenotypic variation. This review aims to identify existing genetic heterogeneity measurements in the psychiatric literature and provides a conceptual review of their mechanisms, limitations, and assumptions. The Scopus database was searched for studies that quantified genetic heterogeneity or correlation of psychiatric phenotypes with human genetic data. Ninety studies were included. Eighty-seven reports quantified genetic correlation, five applied genomic structural equation modelling, three evaluated departure from the Hardy-Weinberg equilibrium at one or more loci, and two applied a novel approach known as MiXeR. We found no study that rigorously measured genetic etiological heterogeneity across a large number of markers. Developing such approaches may help better characterize the biological diversity of psychopathology.

Although resilience has been identified to be moderately heritable, little is known about the genetic variants involved. While there has not yet been a robust genome-wide association study (GWAS) of resilience, existing GWAS of related phenotypes may provide a starting point for developing our understanding of the heritability of resilience. In a sample of older, US adults (N = 9480), we examined the extent to which proxy polygenic scores (PGS) explained the variance in resilience. Four of the 32 PGS assessed (subjective wellbeing, neuroticism, depressive symptoms and educational attainment) reached significance among participants with European ancestries, but with relatively small effects (= 0.002-0.09). Notably, PGSs derived from GWAS of PTSD among participants with either European or African ancestries were uncorrelated with resilience. Even aggregated across all available proxy PGSs, existing PGSs are not sufficient to inform our understanding of the genetics underlying the heritability of resilience. A large-scale GWAS of resilience is needed as it would provide greater insight into the genetic mechanisms underlying the heritability of resilience.

Background: Complement component (3b/4b) receptor 1 (CR1) is an interesting candidate gene which has a close connection with Alzheimer's disease, and its polymorphisms have been reported to link to the late-onset Alzheimer's disease (LOAD) susceptibility. However, the findings of these related studies are inconsistent. Objective To explore the effect of CR1 genetic variants in LOAD susceptibility. MethodsWe searched relevant studies for the period up to 1 November 2020. And odds ratios (ORs) and their 95% confidence intervals (CIs) were utilized to assess the strength of the association. In addition, we carried out a case-control association study to assess their genetic association.

Results: Finally, a total of 30 articles with 30108 LOAD cases and 37895 controls were included. Significant allele frequency between LOAD patients and controls was observed in rs3818361 and rs6656401 (rs3818361, T vs. C: OR,1.18; 95% CI, 1.13-1.23; rs6656401, A vs. G: OR, 1.23; 95% CI, 1.10-1.36). Moreover, these results remain significant in subgroup of rs3818361 in Asia or America (OR,1.26; 95% CI,1.06-1.45; OR, 1.18; 95% CI, 1.13-1.24, respectively) and rs6656401 in Europe (OR = 1.26; 95% CI, 1.09-1.42). In addition, the two single nucleotide polymorphisms were proved to significantly increase LOAD risk in the overall population under the dominant model (OR = 1.12; 95% CI, 1.02-1.21; OR = 1.18, 95% CI, 1.15-1.22, respectively). Our case-control study showed that the distribution of rs6656401 genotype was significant (P = 0.000; OR, 6.889; 95% CI, 2.709-17.520), suggesting the A allele of rs6656401 is the risk allele.

Conclusion: These available data indicate that rs6656401 in CR1 is significant to increase LOAD risk.

Most psychiatric disorders are associated with an elevated risk of suicide. Suicidal behavior is the product of the interaction of many risk factors, such as genetics and environmental factors. Hence, epigenetics research may help to understand the mechanisms leading to suicidal ideation and behavior. This review will discuss epigenetic studies in both suicidal ideation and behavior. Epigenetic modifications are likely to be important in both suicidal ideation and behavior. Most of the reviewed studies found significant epigenetic modifications linked with suicidal behavior rather than ideation. Although sizable research has been carried out on this topic, most studies have been done on small-scale samples, and future research is required in larger samples with better clinical characterization of suicide phenotypes to investigate these epigenetic modifications further.

Introduction: In humans the normal development of cortical regions depends on the complex interactions between a number of proteins that promote the migrations of neuronal precursors from germinal zones and assembly into neuronal laminae. ASTN2 is one of the proteins implicated in such a complex process. Recently it has been observed that ASTN2 also regulates the surface expression of multiple synaptic proteins resulting in a modulation of synaptic activity. Several rare copy number variants (CNVs) in ASTN2 gene were identified in patients with neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASD), attention deficit-hyperactivity disorders and intellectual disability.

Methods: By using comparative genomic hybridization array technology, we analyzed the genomic profiles of five patients of three unrelated families with NDDs. Clinical diagnosis of ASD was established according to the Statistical Manual of Mental Disorders, Fifth Edition (APA 2013) criteria.

Results: We identified new rare CNVs encompassing ASTN2 gene in three unrelated families with different clinical phenotypes of NDDs. In particular, we identified a deletion of about 70 Kb encompassing intron 19, a 186 Kb duplication encompassing the sequence between the 5'-end and the first intron of the gene and a 205 Kb deletion encompassing exons 6-11.

Conclusion: The CNVs reported here involve regions not usually disrupted in patients with NDDs with two of them affecting only the expression of the long isoforms. Further studies will be needed to analyze the impact of these CNVs on gene expression regulation and to better understand their impact on the protein function.

Objective: Emerging evidence suggests that vitamin D might protect from attempted suicide. The study aimed to investigate the associations between single-nucleotide polymorphisms (SNPs) related to vitamin D levels identified in a large genome-wide association study and attempted suicide in rural China.

Methods: This 1:1 matched case-control study included altogether 510 suicide attempters and 510 community controls. Genotypes of four target SNPs (DHCR7-rs12785878, CYP2R1-rs10741657, GC-rs2282679, and CYP24A1-rs6013897) were determined, and a genetic risk score (GRS) was constructed to evaluate the combined effect of them. Demographic and psychological information was acquired through face-to-face interviews.

Results: The A allele of CYP24A1-rs6013897 was significantly associated with attempted suicide (OR = 1.27, 95% CI, 1.03-1.58, P = 0.029), even after adjusting for demographic and psychological confounders (adjusted OR = 1.53, 95% CI, 1.01-2.30, P = 0.043). The GRS analyses revealed a significantly higher risk of attempted suicide with a greater number of low vitamin D alleles (adjusted OR = 1.33, 95% CI, 1.13-1.58, P < 0.001). Subgroup analyses stratified by sex indicated that the genetic associations were only significant among males with adjusted ORs of 3.77 (95% CI, 1.56-9.10) for the A allele of rs6013897 and 2.04 (95% CI, 1.32-3.17) for GRS.

Conclusions: Our findings identity CYP24A1-rs6013897 as a potential biomarker for attempted suicide and indicate that a genetic predisposition to lower vitamin D levels may contribute to attempted suicide. It suggests the possibility that vitamin D may have the preventive potential for attempted suicide.

Etiopathogenesis of autism spectrum disorder (ASD) is highly heterogeneous. Genetic factors play a major role in the etiology of ASD, and 16p11.2 microdeletion is one of the best-known genetic abnormalities thought to be strongly linked to ASD. Conversely, 17q12 microduplication is observed relatively rarely, yet it is reported that 17q12 recurrent duplication also results in a predisposition to ASD. Additionally, 16p11.2 microdeletion is characterized by developmental delay, intellectual disability, ASD and seizures, while 17q12 recurrent duplication is thought to be related to intellectual disability, seizures, eye or vision problems and, rarely, cardiac and renal anomalies. It also has been linked to ASD, schizophrenia, aggression and self-injury. This paper presents two different genetic abnormalities and their relations to ASD. Two siblings were studied; in one of the siblings, maternally originated 17q12 duplication was identified, and paternally originated 16p11.2 microdeletion was identified in the other sibling. To the best of the authors' knowledge, the present paper is a rare case report which shows the coexistence of 17q12 duplication, clubfoot deformity and ASD as well as 16p11.2 microdeletion, spina bifida occulta and ASD.

Stress is an important risk factor for suicidal ideation, but the mechanisms that link stress, suicidal ideation and neurobiology remain unclear. Epigenetic mechanisms are involved in both vulnerability to suicidal behavior and stress. This is a pilot study of 60 patients with schizophrenia spectrum disorders (36 men and 24 women), with an average age of 43.75 ± 12.24 years. We analyzed the effects of (1) perceived stress and (2) the mediation of genome-wide methylation (~450 000 CpG sites) on suicidal ideation severity. The top CpG site mediating the effect of stress on suicidal ideation was the cg10782349 located in the ZNF701 gene on chromosome 19, facilitating the effect through DNA hypermethylation. These preliminary results indicate that DNA methylation in peripheral tissues can clarify the complex relationship between stress and suicidal ideation in schizophrenia.

Background: The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype.

Methods: We assessed the CYP2C19 genotype-predicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the self-rated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results.

Results: Seventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; ηp2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; ηp2  = 0.131 and P = 0.030; ηp2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status.

Conclusions: Intermediate CYP2C19 polymorphism-predicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19-metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.