CACNA1C hypermethylation is associated with bipolar disorder

The CACNA1C gene, encoding a subunit of the L-type voltage-gated calcium channel is one of the best-supported susceptibility genes for bipolar disorder (BD). Genome-wide association studies have identified a cluster of non-coding single-nucleotide polymorphisms (SNPs) in intron 3 to be highly associated with BD and schizophrenia. The mechanism by which these SNPs confer risk of BD appears to be through an altered regulation of CACNA1C expression. The role of CACNA1C DNA methylation in BD has not yet been addressed. The aim of this study was to investigate if CACNA1C DNA methylation is altered in BD. First, the methylation status of five CpG islands (CGIs) across CACNA1C in blood from BD subjects (n=40) and healthy controls (n=38) was determined. Four islands were almost completely methylated or completely unmethylated, while one island (CGI 3) in intron 3 displayed intermediate methylation levels. In the main analysis, the methylation status of CGI 3 was analyzed in a larger sample of BD subjects (n=582) and control individuals (n=319). Out of six CpG sites that were investigated, five sites showed significant hypermethylation in cases (lowest P=1.16 × 10(-7) for CpG35). Nearby SNPs were found to influence the methylation level, and we identified rs2238056 in intron 3 as the strongest methylation quantitative trait locus (P=2.6 × 10(-7)) for CpG35. In addition, we found an increased methylation in females, and no difference between bipolar I and II. In conclusion, we find that CACNA1C methylation is associated with BD and suggest that the regulatory effect of the non-coding risk variants involves a shift in DNA methylation

Analysis of ANK3 and CACNA1C variants identified in bipolar disorder whole genome sequence data

Genetic markers in the genes encoding ankyrin 3 (ANK3) and the α-calcium channel subunit (CACNA1C) are associated with bipolar disorder (BP). The associated variants in the CACNA1C gene are mainly within intron 3 of the gene. ANK3 BP-associated variants are in two distinct clusters at the ends of the gene, indicating disease allele heterogeneity

Whole-exome sequencing of individuals from an isolated population implicates rare risk variants in bipolar disorder

Bipolar disorder affects about 1% of the world's population, and its estimated heritability is about 75%. Only few whole genome or whole-exome sequencing studies in bipolar disorder have been reported, and no rare coding variants have yet been robustly identified. The use of isolated populations might help finding variants with a recent origin, more likely to have drifted to higher frequency by chance. Following this approach, we investigated 28 bipolar cases and 214 controls from the Faroe Islands by whole exome sequencing, and the results were followed-up in a British sample of 2025 cases and 1358 controls. Seventeen variants in 16 genes in the single-variant analysis, and 3 genes in the gene-based statistics surpassed exome-wide significance in the discovery phase. The discovery findings were supported by enrichment analysis of common variants from genome-wide association studies (GWAS) data and interrogation of protein-protein interaction networks. The replication in the British sample confirmed the association with NOS1 (missense variant rs79487279) and NCL (gene-based test). A number of variants from the discovery set were not present in the replication sample, including a novel PITPNM2 missense variant, which is located in a highly significant schizophrenia GWAS locus. Likewise, PIK3C2A identified in the gene-based analysis is located in a combined bipolar and schizophrenia GWAS locus. Our results show support both for existing findings in the literature, as well as for new risk genes, and identify rare variants that might provide additional information on the underlying biology of bipolar disorder

Prevalence and Awareness of Hypertension among a Rural Jazan Population

Background: Hypertension (HTN) is a major global public health problem. Knowledge of the risk factors and repercussions of HTN is crucial to preventing the disease. Rural populations have lower levels of knowledge of the disease than urban populations. However, no studies have assessed the levels of awareness of HTN and their determinants in rural regions of Saudi Arabia. Objectives: This study aimed to assess the awareness of HTN and its determinants among a rural population of Jazan region, Saudi Arabia. Methodology: We conducted a cross-sectional analytical study among six primary healthcare centers selected randomly from the rural areas of Jazan region. We targeted all Saudi adults visiting these centers. Information was gathered using interview questionnaires completed by 607 people. SPSS was utilized to analyze the collected data. Results: In all population groups, the prevalence of diagnosed HTN increased with age, particularly gradually increasing in those aged younger than 40 years and then rapidly and sharply increasing in those aged 40 years and over. The women (43.3%) had a higher prevalence of HTN than the men (34.6%), which is comparable with findings in other areas in Saudi Arabia and the Middle East. Approximately 65.6% of the participants without HTN and 34.4% of the participants with HTN did not know their normal blood pressure. Approximately 61.7% of the participants without HTN and 59.0% of the participants with HTN felt that pharmaceuticals are insufficient in curing HTN, while 60.7% and 64.7% believed that HTN can be cured. Conclusions: The global prevalence of HTN is increasing annually owing to rapid changes in lifestyle and dietary habits. Furthermore, because adherence to antihypertensives is poor in rural Jazan, the Ministry of Health and researchers advocate implementing a program to increase awareness and assess patient adherence to prescribed medication for the control of HTN

Whole-exome sequencing of individuals from an isolated population implicates rare risk variants in bipolar disorder

Bipolar disorder affects about 1% of the world's population, and its estimated heritability is about 75%. Only few whole genome or whole-exome sequencing studies in bipolar disorder have been reported, and no rare coding variants have yet been robustly identified. The use of isolated populations might help finding variants with a recent origin, more likely to have drifted to higher frequency by chance. Following this approach, we investigated 28 bipolar cases and 214 controls from the Faroe Islands by whole exome sequencing, and the results were followed-up in a British sample of 2025 cases and 1358 controls. Seventeen variants in 16 genes in the single-variant analysis, and 3 genes in the gene-based statistics surpassed exome-wide significance in the discovery phase. The discovery findings were supported by enrichment analysis of common variants from genome-wide association studies (GWAS) data and interrogation of protein-protein interaction networks. The replication in the British sample confirmed the association with NOS1 (missense variant rs79487279) and NCL (gene-based test). A number of variants from the discovery set were not present in the replication sample, including a novel PITPNM2 missense variant, which is located in a highly significant schizophrenia GWAS locus. Likewise, PIK3C2A identified in the gene-based analysis is located in a combined bipolar and schizophrenia GWAS locus. Our results show support both for existing findings in the literature, as well as for new risk genes, and identify rare variants that might provide additional information on the underlying biology of bipolar disorder

Health Workers’ Knowledge and Attitude towards Monkeypox in Southwestern Saudi Arabia: A Cross-Sectional Study

Background: Monkeypox outbreaks in non-endemic countries emphasize the importance of being prepared to prevent its progression to a pandemic. To effectively control monkeypox, healthcare providers must have sufficient knowledge and good attitudes and practices to limit its spread. We initiated this project to assess the factors associated with health workers’ knowledge and attitude toward monkeypox in southwestern Saudi Arabia. Methods: We included 398 eligible health workers working at various health facilities. Data was collected using an online survey, and participants had an opportunity to consent. We conducted descriptive statistics for all variables and used chi-square statistics, t-test, and multivariate analysis to establish the association between health workers’ demographic characteristics and knowledge of monkeypox disease. Results: The mean age was 30.93 ± 8.25 years for the included participants, and most of them were between 22 and 29 years, male, single, nurses, working in government hospitals, and had worked for at least five years. The chi-square and t-test showed that the participants’ knowledge level was significantly related to age, marital status, job title, and medical practice. Most of the participants had low knowledge and good attitudes toward monkeypox prevention measures. Multivariate analysis showed that higher knowledge was associated with younger age after controlling all other significant bivariate relationships between knowledge and demographics. Conclusions: This study found low knowledge levels and high good attitude levels of monkeypox among the participants. As such, there is a need to support health workers in understanding monkeypox epidemiology, prevention, and treatment. Therefore, Saudi Arabia will be making significant strides to being well prepared and ready to handle future monkeypox outbreaks