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In Search for the Genetic Basis of Age-Related Complex Traits:...
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In Search for the Genetic Basis of Age-Related Complex Traits: From Single-SNP to Interaction Approaches

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 (15 November 2022) | Viewed by 7302

Special Issue Editors

Dr. Paolina Crocco

E-Mail Website
Guest Editor
Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy
Interests: genetic variability; polymorphisms; aging and longevity; complex traits; telomere; healthy aging; genetic epidemiology; association studies
Special Issues, Collections and Topics in MDPI journals
Dr. Francesco De Rango

E-Mail Website
Guest Editor
Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy
Interests: genetic variability in age-related complex traits; genetic data analysis; epigenetics of aging; healthy aging; genetic epidemiology; association studies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The increasing lifespan in western countries has prompted researchers to focus on molecular mechanisms underlying the individual ability to attain a long and healthy life. Large cohort studies have identified a huge number of weak- to moderate-effect loci associated with age-related diseases, therefore leaving a large part of the genetic variance unsolved. A portion of this “missing heritability” may depend on the effect of rare variants, and also on pleiotropic effects and epistatic interactions among genes. This consideration has moved research from single-SNP analysis to SNP–SNP interaction approaches. For various complex phenotypes, such interaction-based approaches have discovered bridges between different pathways and networks, thus offering new important clues on the underlying molecular mechanisms.

Because progresses in personalized medicine may rely on understanding how specific alleles interact to cause phenotypes, the aim of this Special Issue is to take stock of the situation and point to future directions in this field, by offering to the reader i) new analytical methodologies for performing interaction analysis, especially in large genetic datasets, and ii) papers on genetic interactions which shed a light on the molecular basis of age-related diseases.

Contributions by experts in the field in the form of research articles, reviews, and short communications are called for.

Dr. Paolina Crocco
Dr. Francesco De Rango
Guest Editors

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

  • aging
  • age-related complex traits
  • age-related diseases
  • genetic variability
  • epistatic interactions
  • pleiotropic effects
  • SNP-SNP interaction
  • network analysiskeyword

Published Papers (3 papers)

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Research

13 pages, 14300 KiB  
Article
New Genetically Determined Markers of the Functional State of the Cardiovascular System
by Elena V. Kondakova, Valeria M. Ilina, Lyubov M. Ermakova, Mikhail I. Krivonosov, Kirill V. Kuchin and Maria V. Vedunova
Genes 2023, 14(1), 185; https://0-doi-org.brum.beds.ac.uk/10.3390/genes14010185 - 10 Jan 2023
Viewed by 1457
Abstract
Nowadays, cardiovascular diseases (CVDs) occupy a leading position in population mortality. Since it is known that the development of cardiovascular pathologies is determined mainly by the human genetic burden, an urgent task of primary prevention of CVDs is to assess the contribution of [...] Read more.
Nowadays, cardiovascular diseases (CVDs) occupy a leading position in population mortality. Since it is known that the development of cardiovascular pathologies is determined mainly by the human genetic burden, an urgent task of primary prevention of CVDs is to assess the contribution of gene polymorphism to the formation of cardiovascular risk. The material for the study was the blood of volunteers aged 21 to 102 years. Polymorphisms were determined by real–time PCR. Multichannel volumetric sphygmography was performed to analyze the functional state of the vascular wall. The study revealed that the rs5742904 polymorphism of the ApoB gene was found to be absent in the studied groups of long-livers and descendants of long-livers. Results indicated that the carriage of the heterozygous variant of the MMP9 polymorphism is associated with a favorable prognosis for cardiovascular system functioning. A tendency towards an increase in the rate of biological age acceleration among subgroups with AA and GG genotypes of the MMP9 gene and a negative value of biological age acceleration among heterozygous carriers of this polymorphism allele were found. The conducted studies make it possible to identify new associations of the studied polymorphisms with the functional state of the cardiovascular system, which is of great clinical importance and requires further study. Full article
(This article belongs to the Special Issue In Search for the Genetic Basis of Age-Related Complex Traits: From Single-SNP to Interaction Approaches)
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12 pages, 664 KiB  
Article
Polygenic Models Partially Predict Muscle Size and Strength but Not Low Muscle Mass in Older Women
by Praval Khanal, Christopher I. Morse, Lingxiao He, Adam J. Herbert, Gladys L. Onambélé-Pearson, Hans Degens, Martine Thomis, Alun G. Williams and Georgina K. Stebbings
Genes 2022, 13(6), 982; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13060982 - 30 May 2022
Cited by 6 | Viewed by 2480
Abstract
Background: Heritability explains 45-82% of muscle mass and strength variation, yet polygenic models for muscle phenotypes in older women are scarce. Therefore, the objective of the present study was to (1) assess if total genotype predisposition score (GPSTOTAL) for a set [...] Read more.
Background: Heritability explains 45-82% of muscle mass and strength variation, yet polygenic models for muscle phenotypes in older women are scarce. Therefore, the objective of the present study was to (1) assess if total genotype predisposition score (GPSTOTAL) for a set of polymorphisms differed between older women with low and high muscle mass, and (2) utilise a data-driven GPS (GPSDD) to predict the variance in muscle size and strength-related phenotypes. Methods: In three-hundred 60- to 91-year-old Caucasian women (70.7 ± 5.7 years), skeletal muscle mass, biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VLACSA), hand grip strength (HGS), and elbow flexion (MVCEF) and knee extension (MVCKE) maximum voluntary contraction were measured. Participants were classified as having low muscle mass if the skeletal muscle index (SMI) < 6.76 kg/m2 or relative skeletal muscle mass (%SMMr) < 22.1%. Genotyping was completed for 24 single-nucleotide polymorphisms (SNPs). GPSTOTAL was calculated from 23 SNPs and compared between the low and high muscle mass groups. A GPSDD was performed to identify the association of SNPs with other skeletal muscle phenotypes. Results: There was no significant difference in GPSTOTAL between low and high muscle mass groups, irrespective of classification based on SMI or %SMMr. The GPSDD model, using 23 selected SNPs, revealed that 13 SNPs were associated with at least one skeletal muscle phenotype: HIF1A rs11549465 was associated with four phenotypes and, in descending number of phenotype associations, ACE rs4341 with three; PTK2 rs7460 and CNTFR rs2070802 with two; and MTHFR rs17421511, ACVR1B rs10783485, CNTF rs1800169, MTHFR rs1801131, MTHFR rs1537516, TRHR rs7832552, MSTN rs1805086, COL1A1 rs1800012, and FTO rs9939609 with one phenotype. The GPSDD with age included as a predictor variable explained 1.7% variance of biceps brachii thickness, 12.5% of VLACSA, 19.0% of HGS, 8.2% of MVCEF, and 9.6% of MVCKE. Conclusions: In older women, GPSTOTAL did not differ between low and high muscle mass groups. However, GPSDD was associated with muscle size and strength phenotypes. Further advancement of polygenic models to understand skeletal muscle function during ageing might become useful in targeting interventions towards older adults most likely to lose physical independence. Full article
(This article belongs to the Special Issue In Search for the Genetic Basis of Age-Related Complex Traits: From Single-SNP to Interaction Approaches)
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16 pages, 899 KiB  
Article
Genome-Wide Analysis in Drosophila Reveals the Genetic Basis of Variation in Age-Specific Physical Performance and Response to ACE Inhibition
by Mariann M. Gabrawy, Nick Khosravian, George S. Morcos, Tatiana V. Morozova, Meagan Jezek, Jeremy D. Walston, Wen Huang, Peter M. Abadir and Jeff Leips
Genes 2022, 13(1), 143; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13010143 - 14 Jan 2022
Cited by 4 | Viewed by 2532
Abstract
Despite impressive results in restoring physical performance in rodent models, treatment with renin–angiotensin system (RAS) inhibitors, such as Lisinopril, have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to [...] Read more.
Despite impressive results in restoring physical performance in rodent models, treatment with renin–angiotensin system (RAS) inhibitors, such as Lisinopril, have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to drugs, such as RAS inhibitors, remain unknown. Given the complexity of the relationship between physical traits and genetic background, genomic studies which predict genotype- and age-specific responses to drug treatments in humans or vertebrate animals are difficult. Here, using 126 genetically distinct lines of Drosophila melanogaster, we tested the effects of Lisinopril on age-specific climbing speed and endurance. Our data show that functional response and sensitivity to Lisinopril treatment ranges from significant protection against physical decline to increased weakness depending on genotype and age. Furthermore, genome-wide analyses led to identification of evolutionarily conserved genes in the WNT signaling pathway as being significantly associated with variations in physical performance traits and sensitivity to Lisinopril treatment. Genetic knockdown of genes in the WNT signaling pathway, Axin, frizzled, nemo, and wingless, diminished or abolished the effects of Lisinopril treatment on climbing speed traits. Our results implicate these genes as contributors to the genotype- and age-specific effects of Lisinopril treatment and because they have orthologs in humans, they are potential therapeutic targets for improvement of resiliency. Our approach should be widely applicable for identifying genomic variants that predict age- and sex-dependent responses to any type of pharmaceutical treatment. Full article
(This article belongs to the Special Issue In Search for the Genetic Basis of Age-Related Complex Traits: From Single-SNP to Interaction Approaches)
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