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Genetics of Multifactorial Diseases
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Genetics of Multifactorial Diseases

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (10 February 2024) | Viewed by 5112

Special Issue Editor

Dr. Yiannis Vasilopoulos

E-Mail Website
Guest Editor
Laboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece
Interests: multifactorial diseases; psoriasis; atopic dermatitis; rheumatoid arthritis; pharmacogenetics/pharmacogenomics; molecular biology and functional analysis of genes

Special Issue Information

Dear Colleagues,

Current genetic approaches, with the major example of genome-wide association studies (GWASs), have unveiled numerous associated loci in multifactorial diseases, thus enabling the computation of an individual’s predisposition to a complex trait through polygenic risk scores (PRSs). However, existing approaches are limited to the incorporation of identified common genetic variants that explain a small proportion of the estimated genetic variability, thus excluding the effect of rare variants that have been repeatedly shown to explain the ‘missing heritability’. The clinical and molecular variability in multifactorial diseases is additionally mediated by multi-layered interactions between the genetic component and environmental factors; these gene–environment interactions are depicted from the epigenetic modulations that orchestrate the expression of respective loci. Deciphering the role of rare genetic variants in a trait’s predisposition as well as assessing gene–environment interactions through the functional relevance of the epigenetic modifications could help to form holistic approaches that capture the majority of inter-individual variability, fostering the progression and establishment of personalized approaches in precision medicine and preventive interventions.

Given the increasing research efforts in the putative incorporation of such risk factors in the clinical routine, in the Special Issue of Genes entitled ‘Genetics of Multifactorial Diseases’, we seek to cover the relevant aspects of the genetic and epigenetic factors governing the inter-individual variability in multifactorial diseases, their relative functional role, and their modulation of the clinical phenotype.

Dr. Yiannis Vasilopoulos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multifactorial diseases
  • epigenetics
  • genetic variants
  • polymorphisms
  • gene–environment interactions
  • rare variants
  • polygenic risk scores
  • pharmacogenetics

Published Papers (4 papers)

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Research

19 pages, 791 KiB  
Article
Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders
by Annaluisa Ranieri, Ilaria La Monica, Maria Rosaria Di Iorio, Barbara Lombardo and Lucio Pastore
Genes 2024, 15(4), 427; https://doi.org/10.3390/genes15040427 - 28 Mar 2024
Viewed by 434
Abstract
Neurodevelopmental disorders are a group of complex multifactorial disorders characterized by cognitive impairment, communication deficits, abnormal behaviour, and/or motor skills resulting from abnormal neural development. Copy number variants (CNVs) are genetic alterations often associated with neurodevelopmental disorders. We evaluated the diagnostic efficacy of [...] Read more.
Neurodevelopmental disorders are a group of complex multifactorial disorders characterized by cognitive impairment, communication deficits, abnormal behaviour, and/or motor skills resulting from abnormal neural development. Copy number variants (CNVs) are genetic alterations often associated with neurodevelopmental disorders. We evaluated the diagnostic efficacy of the array-comparative genomic hybridization (a-CGH) method and its relevance as a routine diagnostic test in patients with neurodevelopmental disorders for the identification of the molecular alterations underlying or contributing to the clinical manifestations. In the present study, we analysed 1800 subjects with neurodevelopmental disorders using a CGH microarray. We identified 208 (7%) pathogenetic CNVs, 2202 (78%) variants of uncertain significance (VOUS), and 504 (18%) benign CNVs in the 1800 patients analysed. Some alterations contain genes potentially related to neurodevelopmental disorders including CHRNA7, ANKS1B, ANKRD11, RBFOX1, ASTN2, GABRG3, SHANK2, KIF1A SETBP1, SNTG2, CTNNA2, TOP3B, CNTN4, CNTN5, and CNTN6. The identification of interesting significant genes related to neurological disorders with a-CGH is therefore an essential step in the diagnostic procedure, allowing a better understanding of both the pathophysiology of these disorders and the mechanisms underlying their clinical manifestations. Full article
(This article belongs to the Special Issue Genetics of Multifactorial Diseases)
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14 pages, 932 KiB  
Article
Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients
by Ouliana Ivantsik, Anne John, Kyriaki Kydonopoulou, Konstantinos Mitropoulos, Spyridon Gerou, Bassam R. Ali and George P. Patrinos
Genes 2024, 15(3), 309; https://doi.org/10.3390/genes15030309 - 28 Feb 2024
Viewed by 1189
Abstract
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3–5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3–5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis of the disease: SOD1, FUS, TARDBP and C9orf72. This study aims to provide a comprehensive investigation of genetic variants found in SOD1, FUS and TARDBP genes in Greek sporadic ALS (sALS) cases. Our sequencing analysis of the coding regions of the abovementioned genes that include the majority of the variants that lead to ALS in 32 sALS patients and 3 healthy relatives revealed 6 variants in SOD1, 19 variants in FUS and 37 variants in TARDBP, of which the SOD1 p.D90A and the FUS c.*356G>A (rs886051940) variants have been previously associated with ALS, while two novel nonsense pathogenic variants were also identified, namely FUS p.R241* and TDP-43 p.Y214*. Our study contributes to the worldwide effort toward clarifying the genetic basis of sALS to better understand the disease’s molecular pathology. Full article
(This article belongs to the Special Issue Genetics of Multifactorial Diseases)
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16 pages, 2841 KiB  
Article
MiR-217 Regulates SIRT1 Expression and Promotes Inflammatory and Apoptotic Responses in Osteoarthritis
by Aliki-Alexandra Papageorgiou, Athanasios Roussos, Ioanna Papathanasiou, Charalampos Balis, Theophilos Karachalios, Sokratis E. Varitimidis, Konstantinos N. Malizos and Aspasia Tsezou
Genes 2023, 14(12), 2155; https://doi.org/10.3390/genes14122155 - 29 Nov 2023
Viewed by 963
Abstract
Previous studies have reported miR-217 uregulation in age-related pathologies. We investigated the impact of miR-217-5p on sirtuin 1 (SIRT1) regulation in human osteoarthritic (OA) chondrocytes. MiR-217 target enrichment analyses were performed using three public databases, Gene Ontology and Kyoto Encyclopedia of Genes and [...] Read more.
Previous studies have reported miR-217 uregulation in age-related pathologies. We investigated the impact of miR-217-5p on sirtuin 1 (SIRT1) regulation in human osteoarthritic (OA) chondrocytes. MiR-217 target enrichment analyses were performed using three public databases, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. MiR-217-5p expression levels were quantified in normal and OA chondrocytes. SIRT1 expression levels, nuclear factor kappa-B p65 subunit (NF-κBp65) and p53 acetylation levels, and expression levels of OA-related pro-inflammatory markers [tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), IL-6], pro-apoptotic markers [Bax, pro-caspase 3, cleaved caspase 3] and matrix regulators [matrix metalloproteinase (MMP)-1, MMP-13, MMP-9, Collagen 2 (COL2A1), Aggrecan (ACAN)] were evaluated in miR-217 mimic-treated and/or miR-217 inhibitor-treated OA chondrocytes, with/without subsequent treatment with siRNA against SIRT1 (siSIRT1). MiR-217-5p was upregulated in OA chondrocytes, while target prediction/enrichment analyses revealed SIRT1 as miR-217 target-gene. Deacetylation of NF-κBp65 and p53 in miR-217 inhibitor-treated OA chondrocytes was reversed by siSIRT1 treatment. MiR-217 inhibitor-treated OA chondrocytes showed increased COL2A1, ACAN and decreased IL-1β, IL-6, TNFα, Bax, cleaved caspase 3 and MMPs expression levels, which were reversed following miR-217 inhibitor/siSIRT1 treatment. Our findings highlight the impact of miR-217-5p on SIRT1 downregulation contributing to OA pathogenesis. Full article
(This article belongs to the Special Issue Genetics of Multifactorial Diseases)
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17 pages, 1961 KiB  
Article
Candidate Gene Association Studies in Atopic Dermatitis in Participants of European and Asian Ancestry: A Systematic Review and Meta-Analysis
by Alexandros Pontikas, Charalabos Antonatos, Evangelos Evangelou and Yiannis Vasilopoulos
Genes 2023, 14(7), 1456; https://doi.org/10.3390/genes14071456 - 17 Jul 2023
Cited by 1 | Viewed by 1768
Abstract
Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the [...] Read more.
Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the disease. We systematically screened all studies that explored the association between polymorphisms and AD risks in cases of European and Asian ancestry and synthesized the available evidence through a random-effects meta-analysis. We identified 99 studies that met our inclusion/exclusion criteria that examined 17 candidate loci in Europeans and 14 candidate genes in Asians. We confirmed the significant associations between FLG variants in both European and Asian populations and AD risk, while synthesis of the available data revealed novel loci mapped to IL18 and TGFB1 genes in Europeans and IL12RB1 and MIF in Asians that have not yet been identified by genome-wide association studies. Our findings provide comprehensive evidence for AD risk loci in cases of both European and Asian ancestries, validating previous associations as well as revealing novel loci that could imply previously unexplored biological pathways. Full article
(This article belongs to the Special Issue Genetics of Multifactorial Diseases)
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