scholarly journals GENETICS OF PHOBIC DISORDERS

2021 ◽  
pp. 245-256
Author(s):  
V. Pomohaibo ◽  
O. Berezan ◽  
A. Petrushov
Keyword(s):  
Candidate Genes ◽  
Association Studies ◽  
Meta Analysis ◽  
Molecular Genetic ◽  
Genome Wide Association Studies ◽  
Potential Candidate ◽  
Social Phobias ◽  
Phobic Disorders ◽  
Multifactorial Diseases ◽  
Statistical Validity

At present time, on the basis of genome-wide association studies (GWAS), several authors found linkage of phobic disorders with certain regions of chromosomes – 3q26 (agoraphobia), 14q13 (specific phobias), 16q21 (social phobias), 16q22 (social phobias) and 4q31-q34 (phobic disorders). We propose 19 genes that are localized in these regions and are expressed in the brain: PRKCI, CLDN11, EIF5A2, TNIK, CLCN3, CPE, GLRB, GRIA2, NEK1, NPY2R, NPY5R, RAPGEF2,  TRIM2, SMAD1, ADGRG1, BEAN1, CDH8, DOK4 and KATNB1. Therefore, these genes may be investigated as candidate genes of phobic disorders. Various sources propose 26 potential candidate genes of phobic disorders. Finnish geneticist J. Donner carries out a meta-analysis to study the 8 most probable among them and corroborates statistical validity only for 4 genes: ALAD, CDH2, EPB41L4A and GAD1. First three genes are involved in the social phobias, and fourth is involved in whole phobic disorders. Phobias are heterogeneous and multifactorial diseases. To understand the biological mechanisms of such disorders, to create effective methods for their prevention and treatment, there are needed further intensive molecular genetic studies of these disorders on sufficiently large samples and corroborating these results by other authors.

scholarly journals A meta-analysis of genome-wide association studies for average daily gain and lean meat percentage in two Duroc pig populations

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shenping Zhou ◽  
Rongrong Ding ◽  
Fanming Meng ◽  
Xingwang Wang ◽  
Zhanwei Zhuang ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Growth And Development ◽  
Genetic Architecture ◽  
Association Studies ◽  
Meta Analysis ◽  
Average Daily Gain ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Daily Gain

Abstract Background Average daily gain (ADG) and lean meat percentage (LMP) are the main production performance indicators of pigs. Nevertheless, the genetic architecture of ADG and LMP is still elusive. Here, we conducted genome-wide association studies (GWAS) and meta-analysis for ADG and LMP in 3770 American and 2090 Canadian Duroc pigs. Results In the American Duroc pigs, one novel pleiotropic quantitative trait locus (QTL) on Sus scrofa chromosome 1 (SSC1) was identified to be associated with ADG and LMP, which spans 2.53 Mb (from 159.66 to 162.19 Mb). In the Canadian Duroc pigs, two novel QTLs on SSC1 were detected for LMP, which were situated in 3.86 Mb (from 157.99 to 161.85 Mb) and 555 kb (from 37.63 to 38.19 Mb) regions. The meta-analysis identified ten and 20 additional SNPs for ADG and LMP, respectively. Finally, four genes (PHLPP1, STC1, DYRK1B, and PIK3C2A) were detected to be associated with ADG and/or LMP. Further bioinformatics analysis showed that the candidate genes for ADG are mainly involved in bone growth and development, whereas the candidate genes for LMP mainly participated in adipose tissue and muscle tissue growth and development. Conclusions We performed GWAS and meta-analysis for ADG and LMP based on a large sample size consisting of two Duroc pig populations. One pleiotropic QTL that shared a 2.19 Mb haplotype block from 159.66 to 161.85 Mb on SSC1 was found to affect ADG and LMP in the two Duroc pig populations. Furthermore, the combination of single-population and meta-analysis of GWAS improved the efficiency of detecting additional SNPs for the analyzed traits. Our results provide new insights into the genetic architecture of ADG and LMP traits in pigs. Moreover, some significant SNPs associated with ADG and/or LMP in this study may be useful for marker-assisted selection in pig breeding.

scholarly journals Genome-wide association studies and meta-analysis uncovers new candidate genes for growth and carcass traits in pigs

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205576 ◽  
Author(s):  
Iulia Blaj ◽  
Jens Tetens ◽  
Siegfried Preuß ◽  
Jörn Bennewitz ◽  
Georg Thaller
Keyword(s):  
Candidate Genes ◽  
Association Studies ◽  
Meta Analysis ◽  
Carcass Traits ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Assessment of Osteoarthritis Candidate Genes in a Meta‐Analysis of Nine Genome‐Wide Association Studies

2014 ◽  
Vol 66 (4) ◽  
pp. 940-949 ◽  
Author(s):  
Cristina Rodriguez‐Fontenla ◽  
Manuel Calaza ◽  
Evangelos Evangelou ◽  
Ana M. Valdes ◽  
Nigel Arden ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

Genetics of Pediatric Irritability

2019 ◽  
pp. 149-170
Author(s):  
Meridith L. Eastman ◽  
Ashlee A. Moore ◽  
Roxann Roberson-Nay
Keyword(s):  
Environmental Factors ◽  
Candidate Genes ◽  
Association Studies ◽  
Molecular Genetic ◽  
Human Studies ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
Genome Wide ◽  
Literature Searches ◽  
Selection Of

This chapter provides an overview of behavioral and molecular genetics of pediatric irritability. Literature searches using PubMed and PsycInfo databases yielded 37 relevant animal and human studies on irritability. Studies of rodent and primate models initially suggested a genetic etiology for the trait and influenced selection of candidate genes for study in human studies. Behavioral genetic studies of irritability suggest that pediatric irritability is likely influenced by additive genetic and nonshared unique environmental factors, with little to no influence of dominant genetic or shared family environmental factors. Molecular genetic studies have been largely limited to candidate genes with a few emerging genome-wide association studies (GWAS). Results from the candidate gene literature on irritability are inconclusive, and GWAS in clinical populations has yielded limited findings. Future genetic studies of irritability would benefit from the use of appropriate phenotypic measures, adequate sample sizes, and multimethod and longitudinal approaches.

scholarly journals Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/Cas9-based approach

2018 ◽  
Author(s):  
Benedikt von der Heyde ◽  
Anastasia Emmanouilidou ◽  
Eugenia Mazzaferro ◽  
Silvia Vicenzi ◽  
Ida Höijer ◽  
...  
Keyword(s):  
Heart Rate ◽  
Candidate Genes ◽  
Association Studies ◽  
Meta Analysis ◽  
Automated Analysis ◽  
Zebrafish Embryos ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractA meta-analysis of genome-wide association studies (GWAS) identified eight loci that are associated with heart rate variability (HRV), but candidate genes in these loci remain uncharacterized. We developed an image- and CRISPR/Cas9-based pipeline to systematically characterize candidate genes for HRV in live zebrafish embryos. Nine zebrafish orthologues of six human candidate genes were targeted simultaneously in eggs from fish that transgenically express GFP on smooth muscle cells (Tg[acta2:GFP]), to visualize the beating heart. An automated analysis of repeated 30s recordings of beating atria in 381 live, intact zebrafish embryos at 2 and 5 days post-fertilization highlighted genes that influence HRV (hcn4 and si:dkey-65j6.2 [KIAA1755]); heart rate (rgs6 and hcn4); and the risk of sinoatrial pauses and arrests (hcn4). Exposure to 10 or 25µM ivabradine – an open channel blocker of HCNs – for 24h resulted in a dose-dependent higher HRV and lower heart rate at 5 days post-fertilization. Hence, our screen confirmed the role of established genes for heart rate and rhythm (RGS6 and HCN4); showed that ivabradine reduces heart rate and increases HRV in zebrafish embryos, as it does in humans; and highlighted a novel gene that plays a role in HRV (KIAA1755).

scholarly journals GWAS and Fine-Mapping of Livability and Six Disease Traits in Holstein Cattle

2019 ◽  
Author(s):  
Ellen Freebern ◽  
Daniel JA Santos ◽  
Lingzhao Fang ◽  
Jicai Jiang ◽  
Kristen L. Parker Gaddis ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Fine Mapping ◽  
Association Studies ◽  
Expression Patterns ◽  
Genome Wide Association Studies ◽  
Potential Candidate ◽  
Transcriptome Data ◽  
Mapping Procedure ◽  
Genome Wide ◽  
Cattle Health

AbstractBackgroundHealth traits are of significant economic importance to the dairy industry due to their effects on milk production and associated treatment costs. Genome-wide association studies (GWAS) provide a means to identify associated genomic variants and thus reveal insights into the genetic architecture of complex traits and diseases. The objective of this study is to investigate the genetic basis of seven health traits in dairy cattle and to identify potential candidate genes associated with cattle health using GWAS, fine mapping, and analyses of multitissue transcriptome data.ResultsWe studied cow livability and six direct disease traits, mastitis, ketosis, hypocalcemia, displaced abomasum, metritis, and retained placenta, using de-regressed breeding values and more than three million imputed DNA sequence variants. After data edits and filtering on reliability, phenotypes for 11,880 to 24,699 Holstein bulls were included in the analyses of the seven traits. GWAS was performed using a mixed-model association test, and a Bayesian fine-mapping procedure was conducted to calculate a posterior probability of causality to each variant and gene in the candidate regions. The GWAS results detected a total of eight genome-wide significant associations for three traits, cow livability, ketosis, and hypocalcemia, including the bovine MHC region associated with livability. Our fine-mapping of associated regions reported 20 candidate genes with the highest posterior probabilities of causality for cattle health. Combined with transcriptome data across multiple tissues in cattle, we further exploited these candidate genes to identify specific expression patterns in disease-related tissues and relevant biological explanations such as the expression of GC in the liver and association with mastitis as well as the CCDC88C expression in CD8 cells and association with cow livability.ConclusionsCollectively, our analyses report six significant associations and 20 candidate genes of cattle health. With the integration of multi-tissue transcriptome data, our results provide useful information for future functional studies and better understanding of the biological relationship between genetics and disease susceptibility in cattle.

scholarly journals Perspectives on Low Temperature Tolerance and Vernalization Sensitivity in Barley: Prospects for Facultative Growth Habit

2020 ◽  
Vol 11 ◽  
Author(s):  
María Muñoz-Amatriaín ◽  
Javier Hernandez ◽  
Dustin Herb ◽  
P. Stephen Baenziger ◽  
Anne Marie Bochard ◽  
...  
Keyword(s):  
Low Temperature ◽  
Candidate Genes ◽  
Growth Habit ◽  
Association Studies ◽  
Meta Analysis ◽  
Field Tests ◽  
Temperature Tolerance ◽  
Genome Wide Association Studies ◽  
Low Temperature Tolerance ◽  
A Genome

One option to achieving greater resiliency for barley production in the face of climate change is to explore the potential of winter and facultative growth habits: for both types, low temperature tolerance (LTT) and vernalization sensitivity are key traits. Sensitivity to short-day photoperiod is a desirable attribute for facultative types. In order to broaden our understanding of the genetics of these phenotypes, we mapped quantitative trait loci (QTLs) and identified candidate genes using a genome-wide association studies (GWAS) panel composed of 882 barley accessions that was genotyped with the Illumina 9K single-nucleotide polymorphism (SNP) chip. Fifteen loci including 5 known and 10 novel QTL/genes were identified for LTT—assessed as winter survival in 10 field tests and mapped using a GWAS meta-analysis. FR-H1, FR-H2, and FR-H3 were major drivers of LTT, and candidate genes were identified for FR-H3. The principal determinants of vernalization sensitivity were VRN-H1, VRN-H2, and PPD-H1. VRN-H2 deletions conferred insensitive or intermediate sensitivity to vernalization. A subset of accessions with maximum LTT were identified as a resource for allele mining and further characterization. Facultative types comprised a small portion of the GWAS panel but may be useful for developing germplasm with this growth habit.

Genome-Wide Association Studies Identify Two Novel Loci Conferring Susceptibility to Diabetic Retinopathy in Japanese Patients with Type 2 Diabetes

2021 ◽  
Author(s):  
Minako Imamura ◽  
Atsushi Takahashi ◽  
Masatoshi Matsunami ◽  
Momoko Horikoshi ◽  
Minoru Iwata ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Association Studies ◽  
Meta Analysis ◽  
Japanese Patients ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Stage 1

Abstract Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p < 1.0 × 10−4) in an independent case–control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10−9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11–1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10−8, OR = 1.61, 95% CI 1.36–1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10−6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.

Life Course Adiposity and Alzheimer’s Disease: A Mendelian Randomization Study

2021 ◽  
pp. 1-10
Author(s):  
Xian Li ◽  
Yan Tian ◽  
Yu-Xiang Yang ◽  
Ya-Hui Ma ◽  
Xue-Ning Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Course ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Fat Percentage ◽  
Regression Methods ◽  
Weighted Median

Background: Several studies showed that life course adiposity was associated with Alzheimer’s disease (AD). However, the underlying causality remains unclear. Objective: We aimed to examine the causal relationship between life course adiposity and AD using Mendelian randomization (MR) analysis. Methods: Instrumental variants were obtained from large genome-wide association studies (GWAS) for life course adiposity, including birth weight (BW), childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), and body fat percentage (BFP). A meta-analysis of GWAS for AD including 71,880 cases and 383,378 controls was used in this study. MR analyses were performed using inverse variance weighted (IVW), weighted median, and MR-Egger regression methods. We calculated odds ratios (ORs) per genetically predicted standard deviation (1-SD) unit increase in each trait for AD. Results: Genetically predicted 1-SD increase in adult BMI was significantly associated with higher risk of AD (IVW: OR = 1.03, 95% confidence interval [CI] = 1.01–1.05, p = 2.7×10–3) after Bonferroni correction. The weighted median method indicated a significant association between BW and AD (OR = 0.94, 95% CI = 0.90–0.98, p = 1.8×10–3). We also found suggestive associations of AD with WC (IVW: OR = 1.03, 95% CI = 1.00–1.07, p = 0.048) and WHR (weighted median: OR = 1.04, 95% CI = 1.00–1.07, p = 0.029). No association was detected of AD with childhood BMI and BFP. Conclusion: Our study demonstrated that lower BW and higher adult BMI had causal effects on increased AD risk.

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