scholarly journals The genetic basis of psoriasis

2016 ◽  
Vol 14 (2) ◽  
pp. 197-207
Author(s):  
Nguyễn Thị Kim Liên ◽  
Nguyễn Huy Hoàng
Keyword(s):  
Genetic Basis ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Chromosome 6 ◽  
Disease Manifestation ◽  
Genome Wide ◽  
Increasing Risk ◽  
The Impact ◽  
Main Influence

Psoriasis is a chronic dermatitis disease. Although the disease is not dangerous but it affects patients’s life in many aspects and involving a large number of people in the world. Besides that, psoriasis related to many other diseases such as metabolic disorder, diabetes, cardiovascular disease or can develop into servere arthritis and psoriasis arthritis leading to joint deformities. HLAC gene located on chromosome 6 (locus PSORS1) is known to have an important role in the susceptibility of disease. Besides, investigations showed that psoriasis is controlled by many loci and genes. By using traditional methods and genome wide association studies (GWAS) have been identified 13 loci and many genes involved of disease. However, the role of each locus and gene influence to the susceptibility of disease, presentation of disease, time onset and the links with other diseases have not yet been defined clearly. Among the relevant loci, the PSORS1 locus still considered the main influence on the susceptibility of disease. Noteworthy, the factors of age, gender and race have influences to the disease manifestation of different loci. The studies also provides evidences of the relation of proriasis and increasing risk cardiovascular, hypertension, diabetes and other diseases. So that, by understanding the genetic basis of the disease, the doctors and patients can get orientation in prevention, treatment and minimizing the impact of the disease. In this article, we give a clearer view of the genetic basis of psoriasis.

scholarly journals Transcriptome-wide association study uncovers the role of essential genes in anthracycline-induced cardiotoxicity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Erika N. Scott ◽  
Galen E. B. Wright ◽  
Britt I. Drögemöller ◽  
Jafar S. Hasbullah ◽  
Erandika P. Gunaretnam ◽  
...  
Keyword(s):  
Association Study ◽  
Association Studies ◽  
Chemotherapeutic Agents ◽  
Genome Wide Association Studies ◽  
Gene Set Enrichment ◽  
Genome Wide ◽  
Pathway Analyses ◽  
The Impact ◽  
Identify Gene Expression

AbstractAnthracyclines are highly effective chemotherapeutic agents; however, their clinical utility is limited by severe anthracycline-induced cardiotoxicity (ACT). Genome-wide association studies (GWAS) have uncovered several genetic variants associated with ACT, but the impact of these findings requires further elucidation. We conducted a transcriptome-wide association study (TWAS) using our previous GWAS summary statistics (n = 280 patients) to identify gene expression-related associations with ACT. We identified a genetic association between decreased expression of GDF5 and ACT (Z-score = −4.30, P = 1.70 × 10−5), which was replicated in an independent cohort (n = 845 patients, P = 3.54 × 10−3). Additionally, cell viability of GDF5-silenced human cardiac myocytes was significantly decreased in response to anthracycline treatment. Subsequent gene set enrichment and pathway analyses of the TWAS data revealed that genes essential for survival, cardioprotection and response to anthracyclines, as well as genes involved in ribosomal, spliceosomal and cardiomyopathy pathways are important for the development of ACT.

scholarly journals Identification of a Missense Variant in MFSD12 Involved in Dilution of Phaeomelanin Leading to White or Cream Coat Color in Dogs

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 386 ◽  
Author(s):  
Benoit Hédan ◽  
Edouard Cadieu ◽  
Nadine Botherel ◽  
Caroline Dufaure de Citres ◽  
Anna Letko ◽  
...  
Keyword(s):  
Genetic Basis ◽  
Coat Color ◽  
Association Studies ◽  
Missense Variant ◽  
White Coat ◽  
Genome Wide Association Studies ◽  
Chromosome 20 ◽  
Genome Wide ◽  
Domestication Process

White coat color in mammals has been selected several times during the domestication process. Numerous dog breeds are fixed for one form of white coat color that involves darkly pigmented skin. The genetic basis of this color, due to the absence of pigment in the hairs, was suggested to correspond to extreme dilution of the phaeomelanin, by both the expression of only phaeomelanin (locus E) and its extreme dilution (locus I). To go further, we performed genome-wide association studies (GWAS) using a multiple breed approach. The first GWAS, using 34 white dogs and 128 non-white dogs, including White Shepherds, Poodles, Cotons de Tulear and Bichons allowed us to identify two significantly associated loci on the locus E and a novel locus on chromosome 20. A second GWAS using 15 other breeds presenting extreme phaeomelanin dilution confirmed the position of locus I on the chromosome 20 (position 55 Mb pcorrected = 6 × 10−13). Using whole-genome sequencing, we identified a missense variant in the first exon of MFSD12, a gene recently identified to be involved in human, mouse and horse pigmentation. We confirmed the role of this variant in phaeomelanin dilution of numerous canine breeds, and the conserved role of MFSD12 in mammalian pigmentation.

scholarly journals Tantalizing dilemma in risk prediction from disease scoring statistics

2019 ◽  
Vol 18 (4) ◽  
pp. 211-219 ◽  
Author(s):  
Denis Awany ◽  
Imane Allali ◽  
Emile R Chimusa
Keyword(s):  
Statistical Methods ◽  
Association Studies ◽  
Complex Trait ◽  
Genome Wide Association Studies ◽  
Causal Factors ◽  
Genome Wide ◽  
Host Genetic ◽  
The Impact ◽  
Disease Scoring

Abstract Over the past decade, human host genome-wide association studies (GWASs) have contributed greatly to our understanding of the impact of host genetics on phenotypes. Recently, the microbiome has been recognized as a complex trait in host genetic variation, leading to microbiome GWAS (mGWASs). For these, many different statistical methods and software tools have been developed for association mapping. Applications of these methods and tools have revealed several important findings; however, the establishment of causal factors and the direction of causality in the interactive role between human genetic polymorphisms, the microbiome and the host phenotypes are still a huge challenge. Here, we review disease scoring approaches in host and mGWAS and their underlying statistical methods and tools. We highlight the challenges in pinpointing the genetic-associated causal factors in host and mGWAS and discuss the role of multi-omic approach in disease scoring statistics that may provide a better understanding of human phenotypic variation by enabling further system biological experiment to establish causality.

scholarly journals UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1566
Author(s):  
Ryan S. Nelson ◽  
Nathan D. Seligson ◽  
Sal Bottiglieri ◽  
Estrella Carballido ◽  
Alex Del Cueto ◽  
...  
Keyword(s):  
Association Studies ◽  
Genome Wide Association Studies ◽  
Clinical Implementation ◽  
Drug Label ◽  
Genome Wide ◽  
Starting Dose ◽  
Therapeutic Decision Making ◽  
Meta Analyses ◽  
The Impact

Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses ≥ 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjustments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments.

scholarly journals The Genetic Basis of Hypertriglyceridemia

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Germán D. Carrasquilla ◽  
Malene Revsbech Christiansen ◽  
Tuomas O. Kilpeläinen
Keyword(s):  
Genetic Basis ◽  
Association Studies ◽  
Cumulative Effect ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Risk Variants ◽  
Genome Wide ◽  
Severe Hypertriglyceridemia ◽  
Increased Risk ◽  
Polygenic Scores

Abstract Purpose of Review Hypertriglyceridemia is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. Severe hypertriglyceridemia may sometimes be a monogenic condition. However, in the vast majority of patients, hypertriglyceridemia is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions that elevate triglyceride levels. In this review, we will summarize recent progress in the understanding of the genetic basis of hypertriglyceridemia. Recent Findings More than 300 genetic loci have been identified for association with triglyceride levels in large genome-wide association studies. Studies combining the loci into polygenic scores have demonstrated that some hypertriglyceridemia phenotypes previously attributed to monogenic inheritance have a polygenic basis. The new genetic discoveries have opened avenues for the development of more effective triglyceride-lowering treatments and raised interest towards genetic screening and tailored treatments against hypertriglyceridemia. Summary The discovery of multiple genetic loci associated with elevated triglyceride levels has led to improved understanding of the genetic basis of hypertriglyceridemia and opened new translational opportunities.

scholarly journals Genetic Determinants of Paget’s Disease of Bone

2021 ◽  
Author(s):  
Navnit S. Makaram ◽  
Stuart H. Ralston
Keyword(s):  
Genetic Factors ◽  
Association Studies ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Genome Wide Association Studies ◽  
Paget's Disease Of Bone ◽  
Genome Wide ◽  
Family Based

Abstract Purpose of Review To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders. Recent Findings Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB. Summary Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred.

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