Genetics Research
rs10521432
Population Frequencies12
African
G 0.5899A 0.4101GG 0.453348GA/AG 0.273218AA 0.273434pop=37,045
African American
G 0.59039A 0.40961GG 0.454357GA/AG 0.272176AA 0.273467pop=35,629
African Others
G 0.5777A 0.4223GG 0.427966GA/AG 0.299435AA 0.272599pop=1,416
Asian
G 0.8722A 0.1278GG 0.810784GA/AG 0.122816AA 0.0664pop=4,006
East Asian
G 0.8832A 0.1168GG 0.825839GA/AG 0.11463AA 0.059531pop=3,158
European
G 0.711847A 0.288153GG 0.599583GA/AG 0.22456AA 0.175857pop=222,774
Latin American 1
G 0.7089A 0.2911GG 0.616446GA/AG 0.185146AA 0.198408pop=3,772
Latin American 2
G 0.8641A 0.1359GG 0.82577GA/AG 0.076652AA 0.097578pop=8,512
Other
G 0.7474A 0.2526GG 0.662604GA/AG 0.169441AA 0.167955pop=6,733
Other Asian
G 0.831A 0.169GG 0.754717GA/AG 0.153302AA 0.091981pop=848
South Asian
G 0.668A 0.332GG 0.595122GA/AG 0.146341AA 0.258537pop=410
Studies22
Unread Studies22 ▼
1
Pharmacogenetics of venlafaxine response in older adults with depression and chronic lower back pain
Late-life depression (LLD) and chronic low back pain frequently co-occur and exacerbate one another. Outcomes with antidepressant treatment in this population are often …
2
As dificuldades de aprendizagem escolar, como discalculia e dislexia, são importantes preditores de desfechos na vida adulta, como salário, empregabilidade, equilíbrio emocional etc…
3
Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD). Objectives We used data from a multi‐site, …
4
Late-life depression (LLD), diagnosed as major depressive disorder in older adults (≥ 60 years), is a heterogeneous disorder characterized by a unique constellation of clinical …
5
Brain dysfunction has been proposed for the neurobiological underpinnings of attention-deficit/hyperactivity disorder (ADHD), wherein the'default mode interference hypothesis' is one of the famous neuropsychological models. However, whether this hypothesis is established in adults with ADHD, an extreme phenotype of ADHD, and the association with high-risk genetic variations and treatment outcomes remain unknown. To address these questions, we conducted the voxel-based whole-brain connectome analysis with the resting-state functional MRI data of 84 adults with ADHD and 89 healthy controls to identify connectivity that corresponds to ADHD-related alterations. Then, the candidate genetic data (75 adults with ADHD and 70 healthy controls) and 12-week cognitive behavioral therapy data (14 adults with ADHD) from the same population were leveraged to assess the high-risk genetic variations and treatment outcomes related to these connectivity alterations. Breakdowns of functional connectivity in precuneus and left middle temporal gyrus were found in adults with ADHD. Exactly the connections of what modules contribute to these regions’ abnormalities were subsequently revealed: Decreased connections within the default mode, dorsal and ventral attention modules, and increased connections among them, wherein the middle temporal gyrus served as a crucial ‘bridge’linking the default mode and attention modules. This disrupted connectivity pattern was cross-validated in an independent dataset with 1,018 subjects from the Human Connectome Project by correlating brain connectivity strength with ADHD-related measurements. Significant associations between the altered functional connections and genetic variations in both MAOA and MAOB were also detected. Restoration with treatment in brain function corresponded to the amelioration of connections linked with the middle temporal gyrus, accompanied with improved ADHD core symptoms. These findings demonstrate the interference of default mode on attention in adults with ADHD and its linkage with genetic risk variations and clinical management, thus providing insights into the underlying pathogenesis and potential biomarkers for treatment evaluation.
6
Adults with attention-deficit/hyperactivity disorder (ADHD), as an extreme-phenotype of ADHD, is still facing problems of inconsistency and undeciphered mechanisms for its …
7
The aim of the study was to investigate the association of catechol-O-methyl transferase (COMT) rs4680 and rs4818, and monoamine oxidase type B (MAO-B) rs1799836 and rs6651806 polymorphisms, with anhedonia and other negative symptoms in patients with schizophrenia. This cross-sectional study included 302 patients (58.9% males, median age 42). Main findings: Female carriers of the COMT rs4680 and rs4818 G-allele (related to higher COMT activity) had more severe negative symptoms, compared to females without G allele. COMT rs4818-rs4680 G-G haplotype in females was associated with more severe negative symptoms. Male MAO-B rs1799836 A-allele carriers had more severe alogia than G-allele carriers. Females with physical and social anhedonia had higher frequency of MAO-B rs6651806 A-allele, than females without such anhedonia subtypes, but female A-allele carriers had less severe depressive symptoms than C-allele carriers. Male carriers of MAO-B rs6651806 A-allele had more prominent negative symptoms than C-allele carriers, while MAO-B rs1799836-rs6651806 G-C haplotype in males was associated with less severe negative symptoms. Those findings implicate complex, but sex-specific associations between COMT and MAO-B polymorphisms with anhedonia and negative symptoms in schizophrenia, and highlight the relationship between poorly known MAO-B rs6651806 polymorphism and several symptom domains in schizophrenia.
8
Individuals with intellectual disability (ID) and autism spectrum disorder (ASD) often receive psychotropic medications such as antipsychotics and antidepressants to treat aberrant behaviors and mood symptoms, frequently resulting in polypharmacy and drug-related adverse effects. Pharmacogenomic (PGx) studies with ASD and/or ID (ASD/ID) have been scarce despite the promise of optimizing treatment outcomes. We reviewed the literature on PGx studies with antipsychotics and antidepressants (e.g., treatment response and adverse effects) in ASD/ID.We performed a systematic review using MEDLINE, Embase, and PsycINFO, including peer-reviewed original articles in English referring to PGx in the treatment of ASD/ID in any age groups (e.g., treatment response and adverse effects).A total of 28 PGx studies using mostly candidate gene approaches were identified across age groups. Notably, only 3 studies included adults with ASD/ID while the other 25 studies focused specifically on children/adolescents with ASD/ID. Twelve studies primarily investigated treatment response, of which 5 and 6 studies included patients treated with antipsychotics and antidepressants, respectively. Most interesting results for response were reported for 2 sets of candidate gene studies, namely: (1) The DRD3 Ser9Gly (rs6280) polymorphism was examined in patients treated with risperidone in 3 studies, 2 of which reported an association with risperidone treatment response and (2) the SLC6A4 5-HTTLPR polymorphism and treatment response to antidepressants which was investigated in 4 studies, 3 of which reported significant associations. In regard to side effects, 9 of 15 studies focused on hyperprolactinemia in patients treated with risperidone. Among them, 7 and 5 studies examined the impact of CYP2D6 and DRD2 Taq1A polymorphisms, respectively, yielding mostly negative study findings.There is limited data available on PGx in individuals with ASD/ID and in particular in adults. Given the potential for PGx testing in improving treatment outcomes, additional PGx studies for psychotropic treatment in ASD/ID across age groups are warranted.
9
Juvenile delinquency is related to several biological factors, yet very few vulnerability biomarkers have been identified. Previous data suggest that the enzyme monoamine oxidase B (…
10
Nutritional genomics is comprised of both nutrigenomics and nutrigenetics. Ordovas and Mooser define nutrigenom-ics as the exploration of the effect of nutrients on the genome, …
11
Nutritional genomics is comprised of both nutrigenomics and nutrigenetics. Nutrigenetics looks at the impact of genetics on the interaction between diet and disease risk prediction and is more clearly in scope of practice for medical professionals and genetic counselors. Nutrigenomics studies the measurable influence of nutrition on the genome via the metabolome and proteome and is more clearly in the scope of practice of nutritionists, dietitians, and other advanced health care professionals. Nutrigenomics offers insight into genetic differences in methylation, neurotransmitter synthesis, and detoxification and how to improve these biochemical processes. Central to methylation, the regulatory cycle that influences genomic expression is homocysteine catabolism. Homocysteine is often considered an inflammatory amino acid derivative; however, its regulation plays a primary role not only in epigenetics, but also in detoxification, glutathione generation, and many health conditions. There are two routes of homocysteine recycling and one true disposal route: (1) methionine synthase/methionine synthase reductase (MTR/MTRR), which converts homocysteine back to methionine; (2) betaine homocysteine methyltransferase (BHMT), which also converts homocysteine to methionine; and (3) cystathionine beta synthase (CBS), the only true disposal route that converts homocysteine to cystathionine and, ultimately, leads to the production of sulfate, taurine, and glutathione metabolites. CBS is therefore the transition from methylation to the transsulfuration pathway, which ultimately helps form the endogenous antioxidant glutathione used in phase 2 detoxification. In this way, homocysteine disposal is essential for proper glutathione synthesis. Understanding and influencing this process can help improve various metabolic processes, including turning “on” and “off” genes, synthesizing neurotransmitters, and the production of glutathione for detoxification. In fact, it is important to look beyond methylation to associated pathways including one-carbon metabolism, transsulfuration, the tetrahydrobiopterin (BH4) cycle, and monoamine synthesis. Validation of individual single-nucleotide polymorphism (SNP) activity via laboratory and functional testing allows better insight into the epigenetic activation of genes, further elucidating the mechanisms of nutrient manipulation to improve health.
12
Monoaminooksidaza (MAO) razgrađuje biogene amine, uključujući neurotransmitore dopamin, histamin, serotonin i noradrenalin. Uloga ovog enzima u regulaciji raspoloženja, emocija …
13
Antidepressant response could be from 42 to 50% genetically determined. Venlafaxine (VEN) was the sixth most-prescribed antidepressant in the USA in 2017. Therefore, we reviewed studies which focused on the pharmacogenetics of VEN and found that there is a lack of guidelines for pharmacogenetic testing for VEN. Within investigated genetic polymorphisms, few of them can be indicated as potential predictors of VEN efficacy and tolerance. However, additional pharmacogenetic studies of VEN should be performed to reproduce already obtained results or explain contradictory ones. The individualization of pharmacotherapy is a key issue in providing patients with the highest possible quality of treatment, therefore pharmacogenetic studies should be one of the components of therapy optimization.
14
Methylphenidate (MPH) is a central nervous system stimulant primarily used for the treatment of attention deficit hyperactivity disorder (ADHD). MPH works by preventing the reuptake of dopamine (DA) and norepinephrine (NE) through inhibition of the DA (SLC6A3) and NE transporters (SLC6A2), resulting in an increase in extracellular DA and NE. The bulk of research examining the pharmacodynamics and pharmacogenomics of MPH focuses on SLC6A3, SLC6A2, and their respective genes. Other research on MPH pharmacodynamics analyzes the proteins involved in the processing of neurotransmitters, how altering the concentration of neurotransmitters affects binding to their respective receptors, and the proteins involved in the subsequent downstream effects of these changes. From a pharmacokinetic standpoint, MPH is metabolized primarily by carboxylesterase 1 (CES1). Pharmacokinetics of methylphenidate and pharmacogenetics of carboxylesterase 1 The primary metabolic pathway of MPH involves CES1, primarily expressed in the liver (Fig. 1)[1]. CES1 mediates de-esterification of MPH to the inactive metabolite aphenyl-2-piperidine acetic acid, more commonly known as ritalinic acid (RA). This de-esterification strongly favors the stereoselective hydrolysis of the L-isomer of methylphenidate (L-MPH)[1], resulting in the D-isomer of methylphenidate (dexmethylphenidate, D-MPH) as the primary isomer found in plasma [2]. Further, only D-MPH has been shown to have significant pharmacological activity, with no metabolic conversion between D-MPH and L-MPH [3]. Most formulations of MPH contain a racemic mixture of D-MPH and L-MPH, although there are formulations available of D-MPH alone. Although CES1 is closely related to carboxylesterase 2 (CES2)[4, 5], MPH is metabolized solely by CES1 [1].
15
Type A and B monoamine oxidases (MAO-A, -B) mediate and modulate intracellular signal pathways for survival or death of neuronal cells. MAO-A is associated with development of …
16
SŽS-središnji živčani sustav MKB-10-međunarodna klasifikacija bolesti, deseta revizija DSM-IV-dijagnostički i statistički priručnik za mentalne poremećaje, četvrto izdanje ADHD-…
17
The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine.
18
Pain catastrophizing, a coping style characterized by excessively negative thoughts and emotions in relation to pain, is one of the psychological factors that most markedly predicts variability in the perception of pain; however, only little is known about the underlying neurobiology. The aim of this study was to test for associations between psychological variables, such as pain catastrophizing, anxiety and depression, and selected polymorphisms in genes related to monoaminergic neurotransmission, in particular serotonin pathway genes. Three hundred seventy-nine healthy participants completed a set of psychological questionnaires: the Pain Catastrophizing Scale (PCS), the State-Trait Anxiety Inventory and Beck’s Depression Inventory, and were genotyped for 15 single nucleotide polymorphisms (SNPs) in nine genes. The SNP rs1176744 located in the serotonin receptor 3B gene (5-HTR3B) was found to be associated with pain catastrophizing scores: both the global score and the subscales of magnification and helplessness. This is the first study to show an association between 5-HTR3B and PCS scores, thus suggesting a role of the serotonin pathway in pain catastrophizing. Since 5-HTR3B has previously been associated with descending pain modulation pathways, future studies will be of great interest to elucidate the molecular pathways involved in the relation between serotonin, its receptors and pain catastrophizing.
19
El consumo de tabaco es la principal causa, aislada y evitable, de muerte e invalidez en el mundo desarrollado. La razón es que la nicotina contenida en los cigarros es una sustancia …
20
Nicotine, the primary psychoactive compound in tobacco, is responsible for the addictive effects of smoking; however, there is a paucity of information indicating whether the presence of …
21
… The main finding of the study is that the intronic MAOB polymorphisms rs10521432 and rs6651806 … Post hoc analyses revealed that subjects with allele G at rs10521432 and allele A at …
22
Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder (ASPD). Among males, a functional …
Curated Studies0 ▼
These studies were determined to be useful for this variant — check "Unused Studies" further down if curious what didn't make the cut.
No curated studies yet.
Unused Studies0 ▼
No unused studies.