scholarly journals Arterial calcification, atherosclerosis and osteoporosis: only clinical associations or a genetic platform?

2021 ◽  
Vol 20 (7) ◽  
pp. 3034
Author(s):  
I. A. Skripnikova ◽  
M. A. Kolchina ◽  
A. N. Meshkov ◽  
A. V. Kiseleva ◽  
O. M. Drapkina
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Genetic Markers ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Calcium Deposition ◽  
Arterial Calcification ◽  
Cochrane Library ◽  
Mineral Density ◽  
A Genome

The review is devoted to the comorbidity of two multifactorial diseases  — atherosclerosis and osteoporosis. Numerous epidemiological, experimental and clinical studies have confirmed the relationship between these diseases based on common risk factors and pathogenetic mechanisms. At the same time, to assess the associations between osteoporosis and atherosclerosis-related cardiovascular diseases, the following surrogate markers are used: vascular calcification, vascular stiffness, bone mineral density. It is known that atherosclerosis and osteoporosis depend on the human genotype, and they are caused by the interaction between the environment and genes. The modifiable risk factors for these diseases are largely similar, and the common features of atherosclerosis and osteoporosis pathogenesis make it possible to formulate the concept of a unified genetic basis of their development. Advances in molecular technology have made it possible to conduct a genome-wide association study (GWAS) and successfully identify genetic markers associated with both atherosclerosis and osteoporosis. The review aim was to describe the genes associated with developing atherosclerosis, arterial calcification and osteoporosis, as well as to provide information on the current understanding of the general genetic basis for plaque formation, vascular calcium deposition, and a decrease in bone mass. The analysis of publications from the PubMed, Medline, Web of Science and Cochrane Library databases since 2000 have been carried out. The article describes the genetic markers associated with atherosclerosis and osteoporosis, as well as considers the achievements in studying genetics of osteoporosis and atherosclerosis-related cardiovascular diseases. In addition, modern approaches and directions for further research of these diseases was established. The review can be useful for medical practitioners to clarify various genetic associations and mechanisms that lead to this comorbidity.

scholarly journals Genetic basis and identification of candidate genes for wooden breast and white striping in commercial broiler chickens

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juniper A. Lake ◽  
Jack C. M. Dekkers ◽  
Behnam Abasht
Keyword(s):  
Candidate Genes ◽  
Broiler Chickens ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Specific Protein ◽  
Chromosome 11 ◽  
A Genome ◽  
White Striping ◽  
Commercial Broiler ◽  
Wooden Breast

AbstractWooden breast (WB) and white striping (WS) are highly prevalent and economically damaging muscle disorders of modern commercial broiler chickens characterized respectively by palpable firmness and fatty white striations running parallel to the muscle fiber. High feed efficiency and rapid growth, especially of the breast muscle, are believed to contribute to development of such muscle defects; however, their etiology remains poorly understood. To gain insight into the genetic basis of these myopathies, a genome-wide association study was conducted using a commercial crossbred broiler population (n = 1193). Heritability was estimated at 0.5 for WB and WS with high genetic correlation between them (0.88). GWAS revealed 28 quantitative trait loci (QTL) on five chromosomes for WB and 6 QTL on one chromosome for WS, with the majority of QTL for both myopathies located in a ~ 8 Mb region of chromosome 5. This region has highly conserved synteny with a portion of human chromosome 11 containing a cluster of imprinted genes associated with growth and metabolic disorders such as type 2 diabetes and Beckwith-Wiedemann syndrome. Candidate genes include potassium voltage-gated channel subfamily Q member 1 (KCNQ1), involved in insulin secretion and cardiac electrical activity, lymphocyte-specific protein 1 (LSP1), involved in inflammation and immune response.

Association of SUMOlation Pathway Genes With Stroke in a Genome-wide Association Study in India

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012258
Author(s):  
Amit Kumar ◽  
Ganesh Chauhan ◽  
Shriram Sharma ◽  
Surekha Dabla ◽  
P.N Sylaja ◽  
...  
Keyword(s):  
Risk Factors ◽  
Association Study ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Small Vessel Disease ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Distribution Width ◽  
A Genome ◽  
Single Marker

Objective:To undertake a genomewide association study (GWAS) to identify genetic variants for stroke in Indians.Methods:In a hospital-based case-control study, eight teaching hospitals in India recruited 4,088 subjects, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed using logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked.Results:Association of vascular risk factors with stroke were similar to previous reports, and show modifiable risk factors like hypertension, smoking, and alcohol consumption having the highest effect. Single-marker based association revealed two loci for cardioembolic stroke (1p21 and 16q24), two for small vessel disease stroke (3p26 and 16p13), and four for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at P<5×10-8. The index SNP of 1p21 is an eQTL (Plowest=1.74×10-58) for RWDD3 involved in SUMOlation and is associated with platelet distribution width (1.15×10-9) and 18-carbon fatty acid metabolism (P=7.36×10-12). In gene-based analysis we identified three genes (SLC17A2, FAM73A and OR52L1) at P<2.7×10-6. 11 of 32 candidate gene loci studied in Indians replicated (P<0.05), and 21 of 32 loci identified through previous GWAS replicated based on directionality of effect.Conclusions:This first GWAS of stroke in Indians identified novel loci and replicated previously known loci. For the first time, genetic variants in the SUMOlation pathway which has been implicated in brain ischemia were identified.

scholarly journals The Genetic Basis of Natural Variation in Drosophila melanogaster Immune Defense against Enterococcus faecalis

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 234 ◽  
Author(s):  
Joanne R Chapman ◽  
Maureen A Dowell ◽  
Rosanna Chan ◽  
Robert L Unckless
Keyword(s):  
Drosophila Melanogaster ◽  
Enterococcus Faecalis ◽  
Natural Variation ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Immune Defense ◽  
Nucleotide Polymorphisms ◽  
Disease Response ◽  
A Genome

Dissecting the genetic basis of natural variation in disease response in hosts provides insights into the coevolutionary dynamics of host-pathogen interactions. Here, a genome-wide association study of Drosophila melanogaster survival after infection with the Gram-positive entomopathogenic bacterium Enterococcus faecalis is reported. There was considerable variation in defense against E. faecalis infection among inbred lines of the Drosophila Genetics Reference Panel. We identified single nucleotide polymorphisms associated with six genes with a significant (p < 10−08, corresponding to a false discovery rate of 2.4%) association with survival, none of which were canonical immune genes. To validate the role of these genes in immune defense, their expression was knocked-down using RNAi and survival of infected hosts was followed, which confirmed a role for the genes krishah and S6k in immune defense. We further identified a putative role for the Bomanin gene BomBc1 (also known as IM23), in E. faecalis infection response. This study adds to the growing set of association studies for infection in Drosophila melanogaster and suggests that the genetic causes of variation in immune defense differ for different pathogens.

scholarly journals Lack of association between modifiable exposures and glioma risk: A Mendelian randomisation analysis

2019 ◽  
Author(s):  
Charlie N Saunders ◽  
Alex J Cornish ◽  
Ben Kinnersley ◽  
Philip J Law ◽  
Elizabeth B Claus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genome Wide Association Study ◽  
Iron Status ◽  
Dietary Factors ◽  
Inflammatory Factors ◽  
Mendelian Randomisation ◽  
Omega 3 ◽  
Fat Percentage ◽  
A Genome ◽  
Glioma Risk

Abstract Background The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian Randomisation (MR) framework to examine if lifestyle, cardiometabolic and inflammatory factors influence the risk of glioma. This methodology reduces bias from confounding and is not affected by reverse causation. Methods We identified genetic instruments for 37 potentially modifiable risk factors and evaluated their association with glioma risk using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. We used the estimated odds ratio of glioma associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: lifestyle and dietary factors (height, plasma IGF-1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamin [A1, B12, B6, E and 25-hydroxyvitamin D], fatty acids levels [mono-unsaturated, omega-3 and omega-6] and circulating fetuin-A); cardiometabolic factors (birth weight, HDL cholesterol, LDL cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, HbA1C levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio) were included; inflammatory factors (C-reactive protein (CRP), plasma IL-6 sRa and serum IgE). Results After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism (SNP) no significant association with glioma risk was observed (i.e. PCorrected > 0.05). Conclusions This study did not provide evidence supporting any of the 37 factors examined as having a significant influence on glioma risk.

scholarly journals Optimizing the Power to Identify the Genetic Basis of Complex Traits with Evolve and Resequence Studies

2019 ◽  
Vol 36 (12) ◽  
pp. 2890-2905 ◽  
Author(s):  
Christos Vlachos ◽  
Robert Kofler
Keyword(s):  
Complex Traits ◽  
Quantitative Traits ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Selection Regime ◽  
Genome Wide ◽  
A Genome ◽  
Higher Power ◽  
Powerful Approach ◽  
Next Generation Sequencing Ngs

Abstract Evolve and resequence (E&R) studies are frequently used to dissect the genetic basis of quantitative traits. By subjecting a population to truncating selection for several generations and estimating the allele frequency differences between selected and nonselected populations using next-generation sequencing (NGS), the loci contributing to the selected trait may be identified. The role of different parameters, such as, the population size or the number of replicate populations has been examined in previous works. However, the influence of the selection regime, that is the strength of truncating selection during the experiment, remains little explored. Using whole genome, individual based forward simulations of E&R studies, we found that the power to identify the causative alleles may be maximized by gradually increasing the strength of truncating selection during the experiment. Notably, such an optimal selection regime comes at no or little additional cost in terms of sequencing effort and experimental time. Interestingly, we also found that a selection regime which optimizes the power to identify the causative loci is not necessarily identical to a regime that maximizes the phenotypic response. Finally, our simulations suggest that an E&R study with an optimized selection regime may have a higher power to identify the genetic basis of quantitative traits than a genome-wide association study, highlighting that E&R is a powerful approach for finding the loci underlying complex traits.

scholarly journals Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study

2009 ◽  
Vol 8 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Simon Mead ◽  
Mark Poulter ◽  
James Uphill ◽  
John Beck ◽  
Jerome Whitfield ◽  
...  
Keyword(s):  
Risk Factors ◽  
Association Study ◽  
Genetic Risk ◽  
Genome Wide Association Study ◽  
Genetic Risk Factors ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Jakob Disease

scholarly journals Genomic insights into the origin, domestication and genetic basis of agronomic traits of castor bean

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei Xu ◽  
Di Wu ◽  
Tianquan Yang ◽  
Chao Sun ◽  
Zaiqing Wang ◽  
...  
Keyword(s):  
Castor Bean ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
De Novo ◽  
Agronomic Traits ◽  
Ricinus Communis ◽  
Oilseed Crop ◽  
A Genome ◽  
Trait Locus ◽  
Wild Progenitors

Abstract Background Castor bean (Ricinus communis L.) is an important oil crop, which belongs to the Euphorbiaceae family. The seed oil of castor bean is currently the only commercial source of ricinoleic acid that can be used for producing about 2000 industrial products. However, it remains largely unknown regarding the origin, domestication, and the genetic basis of key traits of castor bean. Results Here we perform a de novo chromosome-level genome assembly of the wild progenitor of castor bean. By resequencing and analyzing 505 worldwide accessions, we reveal that the accessions from East Africa are the extant wild progenitors of castor bean, and the domestication occurs ~ 3200 years ago. We demonstrate that significant genetic differentiation between wild populations in Kenya and Ethiopia is associated with past climate fluctuation in the Turkana depression ~ 7000 years ago. This dramatic change in climate may have caused the genetic bottleneck in wild castor bean populations. By a genome-wide association study, combined with quantitative trait locus analysis, we identify important candidate genes associated with plant architecture and seed size. Conclusions This study provides novel insights of domestication and genome evolution of castor bean, which facilitates genomics-based breeding of this important oilseed crop and potentially other tree-like crops in future.

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