Exploring the associations between genetic variants in genes encoding for subunits of calcium channel and subtypes of bipolar disorder

2014 ◽  
Vol 157 ◽  
pp. 80-86 ◽  
Author(s):  
Wen-Chi Jan ◽  
Shi-Yi Yang ◽  
Li-Chung Chuang ◽  
Ru-Band Lu ◽  
Ming-Kun Lu ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Calcium Channel ◽  
Genetic Variants ◽  
Genes Encoding

scholarly journals Putative second hit rare genetic variants in families with seemingly GBA-associated Parkinson’s disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Muhammad Aslam ◽  
Nirosiya Kandasamy ◽  
Anwar Ullah ◽  
Nagarajan Paramasivam ◽  
Mehmet Ali Öztürk ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Rare Variants ◽  
Alpha Synuclein ◽  
Younger Age ◽  
Targeted Treatments ◽  
Genes Encoding ◽  
Rare Genetic Variants

AbstractRare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson’s disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments.

scholarly journals Association between Polymorphism rs1799732 of DRD2 Dopamine Receptor Gene and Personality Traits among MMA Athletes

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1217
Author(s):  
Marta Niewczas ◽  
Anna Grzywacz ◽  
Katarzyna Leźnicka ◽  
Krzysztof Chmielowiec ◽  
Jolanta Chmielowiec ◽  
...  
Keyword(s):  
High Risk ◽  
Personality Traits ◽  
Dopamine Receptor ◽  
Martial Arts ◽  
Genetic Variants ◽  
Receptor Gene ◽  
Harm Avoidance ◽  
Novelty Seeking ◽  
Genes Encoding ◽  
Dopamine Receptor Gene

Four factors—namely, harm avoidance, novelty seeking, reward addiction and persistence—represent the nature of temperament that is not genetically determined in itself. It was shown in earlier studies that a strong propensity to look for novelty or a tendency to engage in risky behavior is correlated with genetic variants in the area of the genes encoding dopamine receptors. Therefore, the aim of this study is to determine whether there is a relationship between personality traits and genetic variants in the area of the DRD2 dopamine receptor gene in MMA athletes. The participants consisted of 85 mixed martial arts (MMA) athletes and 284 healthy, non-MMA male participants. Their personality traits were measured using the Revised Temperament and Character Inventory. Blood was collected for genetic assays and all samples were genotyped using the real-time PCR method. We observed a statistically significant effect of a complex factor of the DRD2 rs1799732 genotype on MMA participants’ control and reward dependence. Engaging in high-risk sport may be associated with several personality characteristics. The DRD2 rs1799732 polymorphism may be associated with reduced harm avoidance in martial arts athletes, thereby modulating athletes’ predisposition to participate in high-risk sport.

Extracting a needle from a haystack: reanalysis of whole genome data reveals a readily translatable finding

2009 ◽  
Vol 39 (8) ◽  
pp. 1231-1235 ◽  
Author(s):  
R. Keers ◽  
A. E. Farmer ◽  
K. J. Aitchison
Keyword(s):  
Bipolar Disorder ◽  
Calcium Channel ◽  
Unmet Need ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Genome Data ◽  
Early Results ◽  
Genome Association ◽  
Genome Study

There is significant unmet need for more effective treatments for bipolar disorder. The drug discovery process is becoming prohibitively expensive. Hence, biomarker clues to assist or shortcut this process are now widely sought. Using the publicly available data from the whole genome association study conducted by the Wellcome Trust Case Control Consortium, we sought to identify groups of genetic markers (single nucleotide polymorphisms) in which each marker was independently associated with bipolar disorder, with a less stringent threshold than that set by the original investigators (p⩽1×10−4). We identified a group of markers occurring within the CACNA1C gene (encoding the alpha subunit of the calcium channel Cav1.2). We then ascertained that this locus had been previously associated with the disorder in both a smaller and a whole genome study, and that a number of drugs blocking this channel (including verapamil and diltiazem) had been trialled in the treatment of bipolar disorder. The dihydropyridine-based blockers such as nimodipine that bind specifically to Cav1.2 and are more penetrant to the central nervous system have shown some promising early results; however, further trials are indicated. In addition, migraine is commonly seen in affective disorder, and calcium channel antagonists are successfully used in the treatment of migraine. One such agent, flunarizine, is structurally related to other first-generation derivatives of antihistamines such as antipsychotics. This implies that flunarizine could be useful in the treatment of bipolar disorder, and, furthermore, that other currently licensed drugs should be investigated for antagonism of Cav1.2.

scholarly journals Genetic Variation in Blood Pressure and Lifetime Risk of Peripheral Artery Disease: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Michael G Levin ◽  
Derek Klarin ◽  
Venexia M Walker ◽  
Dipender Gill ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Peripheral Artery Disease ◽  
Genetic Correlations ◽  
Channel Blockers ◽  
Peripheral Artery ◽  
Antihypertensive Medications ◽  
Increased Risk ◽  
Genes Encoding ◽  
Artery Disease

Aims: We aimed to estimate the effect of blood pressure and blood pressure lowering medications (via genetic proxies) on peripheral artery disease. Methods and Results: GWAS summary statistics were obtained for BP (International Consortium for Blood Pressure + UK Biobank GWAS; N = up to 757,601 individuals), peripheral artery disease (PAD; VA Million Veteran Program; N = 24,009 cases, 150,983 controls), and coronary artery disease (CAD; CARDIoGRAMplusC4D 1000 Genomes; N = 60,801 cases, 123,504 controls). Genetic correlations between systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and CAD and PAD were estimated using LD score regression. The strongest correlation was between SBP and CAD (rg = 0.36; p = 3.9 x 10-18). Causal effects were estimated by two-sample MR using a range of pleiotropy-robust methods. Increased SBP, DBP, and PP increased risk of both PAD (SBP OR 1.25 [1.19-1.31] per 10mmHg increase, p = 3 x 10-18; DBP OR 1.27 [1.17-1.39], p = 4 x 10-8; PP OR 1.51 [1.38-1.64], p = 1 x 10-20) and CAD (SBP OR 1.37 [1.29-1.45], p = 2 x 10-24; DBP OR 1.6 [1.45-1.76], p = 7 x 10-22; PP OR 1.56 [1.4-1.75], p = 1 x 10-15). The effects of SBP and DBP were greater for CAD than PAD (pdiff = 0.024 for SBP, pdiff = 4.9 x 10-4 for DBP). Increased liability to PAD increased PP (beta = 1.04 [0.62-1.45] mmHg per 1 unit increase in log-odds in liability to PAD, p = 1 x 10-6). MR was also used to estimate the effect of BP lowering through different classes of antihypertensive medications using genetic instruments containing BP-trait associated variants located within genes encoding protein targets of each medication. SBP lowering via calcium channel blocker-associated variants was protective of CAD (OR 0.38 per 10mmHg decrease in SBP; 95% CI 0.19-0.77; p = 0.007). Conclusions: Higher BP is likely to cause both PAD and CAD but may have a larger effect on CAD risk. BP-lowering through calcium-channel blockers (as proxied by genetic variants) decreased risk of CAD.

scholarly journals Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

2020 ◽  
Vol 9 (8) ◽  
pp. 2510
Author(s):  
Katerina Pavelcova ◽  
Jana Bohata ◽  
Marketa Pavlikova ◽  
Eliska Bubenikova ◽  
Karel Pavelka ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Genetic Variants ◽  
Biochemical Parameters ◽  
Previous Analysis ◽  
Direct Sequencing ◽  
Low Frequency ◽  
European Population ◽  
The Body ◽  
Genes Encoding

Urate transporters, which are located in the kidneys, significantly affect the level of uric acid in the body. We looked at genetic variants of genes encoding the major reabsorption proteins GLUT9 (SLC2A9) and URAT1 (SLC22A12) and their association with hyperuricemia and gout. In a cohort of 250 individuals with primary hyperuricemia and gout, we used direct sequencing to examine the SLC22A12 and SLC2A9 genes. Identified variants were evaluated in relation to clinical data, biochemical parameters, metabolic syndrome criteria, and our previous analysis of the major secretory urate transporter ABCG2. We detected seven nonsynonymous variants of SLC2A9. There were no nonsynonymous variants of SLC22A12. Eleven variants of SLC2A9 and two variants of SLC22A12 were significantly more common in our cohort than in the European population (p = 0), while variants p.V282I and c.1002+78A>G had a low frequency in our cohort (p = 0). Since the association between variants and the level of uric acid was not demonstrated, the influence of variants on the development of hyperuricemia and gout should be evaluated with caution. However, consistent with the findings of other studies, our data suggest that p.V282I and c.1002+78A>G (SLC2A9) reduce the risk of gout, while p.N82N (SLC22A12) increases the risk.

Genetics of schizoaffective disorder

2011 ◽  
Vol 08 (02) ◽  
pp. 82-90
Author(s):  
N. Craddock
Keyword(s):  
Bipolar Disorder ◽  
Mood Disorder ◽  
Clinical Features ◽  
Schizoaffective Disorder ◽  
Genetic Variants ◽  
Gene Families ◽  
Clinical Pattern ◽  
Current Usage ◽  
Disease Entities ◽  
Traditional Approaches

Summary“Schizoaffective” refers to a mix of clinical features associated with prototypical schizophrenia and prototypical bipolar disorder. Such cases are common but definitions have varied substantially. Nosological possibilities considered include (a) a form of schizophrenia, (b) a form of mood disorder, (c) a distinct disorder, (d) some mixture of (a)-(c). In current usage “schizoaffective disorder” tends to be used only when cases cannot be fitted to definitions of schizophrenia or bipolar disorder and such cases have been under-represented in cases collections to date. Methodological and practicalissues continue to cause difficulty for accumulating robust knowledge about schizoaffectivedisorder. Here we consider genetic understanding of schizoaffective disorder, particularly recent findings. These show that bipolar disorder andschizophrenia are not completely separate disease entities and confirm that schizoaffectivedisorder is genetically related to both. Some genetic variants influencerisk broadly across the mood-psychosis spectrum (e.g. Variation at CACNA1C). Some studies have implicated common variation at specific genes and gene families as conferring relatively specific phenotypic risk for a schizoaffective-type clinical pattern (e.g. GABAA receptorgenes). Such findings are of great interest and offer promise ofgreat advances in understanding over the next 20 years. It is important that there is a willingnessof researchers to study schizoaffective cases and to use approaches to phenotypic assessmentand classification that go beyond the traditional approaches enshrined within DSM and ICD.

scholarly journals Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes—A Narrative Review of the Case of Vitamins

2020 ◽  
Vol 7 ◽  
Author(s):  
Aikaterini Niforou ◽  
Valentini Konstantinidou ◽  
Androniki Naska
Keyword(s):  
Vitamin D ◽  
Vitamin C ◽  
Genetic Variants ◽  
Current Knowledge ◽  
Association Studies ◽  
Genetic Variations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Dietary Intakes ◽  
Genes Encoding

Recent advances in the field of nutrigenetics have provided evidence on how genetic variations can impact the individuals' response to dietary intakes. An objective and reliable assessment of dietary exposures should rely on combinations of methodologies including frequency questionnaires, short-term recalls or records, together with biological samples to evaluate markers of intake or status and to identify genetic susceptibilities. In an attempt to present current knowledge on how genetic fingerprints contribute to an individual's nutritional status, we present a review of current literature describing associations between genetic variants and levels of well-established biomarkers of vitamin status in free-living and generally healthy individuals. Based on the outcomes of candidate gene, genome-wide-association studies and meta-analyses thereof, we have identified several single nucleotide polymorphisms (SNPs) involved in the vitamins' metabolic pathways. Polymorphisms in genes encoding proteins involved in vitamin metabolism and transport are reported to have an impact on vitamin D status; while genetic variants of vitamin D receptor were most frequently associated with health outcomes. Genetic variations that can influence vitamin E status include SNPs involved in its uptake and transport, such as in SCAR-B1 gene, and in lipoprotein metabolism. Variants of the genes encoding the sodium-dependent vitamin C transport proteins are greatly associated with the body's status on vitamin C. Regarding the vitamins of the B-complex, special reference is made to the widely studied variant in the MTHFR gene. Methodological attributes of genetic studies that may limit the comparability and interpretability of the findings are also discussed. Our understanding of how genes affect our responses to nutritional triggers will enhance our capacity to evaluate dietary exposure and design personalized nutrition programs to sustain health and prevent disease.

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