About this Research Topic
The recent advances in high-throughput sequencing studies, integrated with findings derived from multimodal brain imaging data analyses and genome-wide association studies (GWAS) have expanded our understanding of the genetic architecture of neurodegenerative diseases, transitioning from the simplistic view of Mendel’s theory towards a holistic understanding capable of capturing the entire spectrum of genetic and non-genetic factors contributing to phenotypic manifestation.
Integrating all stochastic components capable of capturing the impact of complex non-additive genetic influences, ranging from gene-gene interactions to gene-by-environment and epigenetics-gene interactions, would be highly effective for gaining insight into the genetic architecture of neurodegenerative diseases. Additionally, biological-specific regulatory networks have emerged as powerful computational or experimental approaches for investigating the integrative framework architecture of biological systems. Disentangling the genetic architecture of complex diseases could greatly benefit from creating integrated, multidimensional biological networks through machine learning (ML)-driven methods based on various omics layers.
The aim of this proposed Research Topic, titled "Understanding the Genetic Architecture of Neurodegenerative Diseases: From Simple to Complex Network Landscapes," is to advance our understanding of the genetic architecture of neurodegenerative diseases. Hence, the objective is to assemble field experts to explore the current state of knowledge concerning how distinct genetic variation contributes to neurodegenerative diseases. In pursuit of this goal, we will gather a series of research papers focusing on the investigation of additional common susceptibility variants within established loci, rare genetic variants, non-coding variants, structural variations, epigenetic influences, epistatic interactions, pleiotropy effects, or other intricate mechanisms, deemed as significant determinants contributing to still-missing genetic components underlying these conditions.
In that sense, it would be helpful to discuss the genetic architecture as a continuum of complexities that underpins a spectrum of inheritance, ranging from monogenic to oligogenic as an intermediate construct, or polygenic architecture, and towards the omnigenic model capable of pinpointing the interconnected nature of biological networks. Furthermore, a comprehensive integration of multi-omics data is necessary to grasp the fundamental principles of neurobiological systemic frameworks in neurodegenerative diseases. These results could enhance our capability to predict and map contextually relevant molecular interactions contributing to endophenotype biology or shared mechanisms among neurodegenerative diseases.
We welcome submissions from researchers and clinicians related to the following topics, including but not limited to:
(1) How do rare and ultra-rare causative alleles, along with genetic interactions, explain the disease etiology and fraction of missing heritability?
(2) What is the impact of structural variations on the genetic architecture of neurodegenerative diseases – a hidden layer of genetic variation?
(3) What are the underlying factors that drive the complex genetic architecture of neurodegenerative diseases, including genetic modifiers, common familial and/or polygenic elements, and epigenetic alterations?
(4) Combining structural and functional multimodal neuroimaging datasets with genomic data offers a promising avenue to illustrate the systematic characterization of neurodegenerative pathologies.
(5) To what extent does the genetic background influence the earliest formation and propagation of pathological mechanisms that underpin a continuum between neurodegenerative diseases?
(6) The multi-omics characterization of patients creates an opportunity to develop new approaches for the classification of neurodegenerative diseases - multidimensional data integration.
(7) A more complete picture of polygenicity via network analysis of neurodegenerative disease can contribute to an integrative perspective on pathological changes.
Manuscripts must be submitted in accordance with the guidelines for Frontiers in Neurology. We look forward to receiving contributions that will improve our understanding of the genetic architecture of neurodegenerative diseases fostering progress in disease diagnosis, prevention, therapeutic interventions, and prognostic assessments.
Integrating all stochastic components capable of capturing the impact of complex non-additive genetic influences, ranging from gene-gene interactions to gene-by-environment and epigenetics-gene interactions, would be highly effective for gaining insight into the genetic architecture of neurodegenerative diseases. Additionally, biological-specific regulatory networks have emerged as powerful computational or experimental approaches for investigating the integrative framework architecture of biological systems. Disentangling the genetic architecture of complex diseases could greatly benefit from creating integrated, multidimensional biological networks through machine learning (ML)-driven methods based on various omics layers.
The aim of this proposed Research Topic, titled "Understanding the Genetic Architecture of Neurodegenerative Diseases: From Simple to Complex Network Landscapes," is to advance our understanding of the genetic architecture of neurodegenerative diseases. Hence, the objective is to assemble field experts to explore the current state of knowledge concerning how distinct genetic variation contributes to neurodegenerative diseases. In pursuit of this goal, we will gather a series of research papers focusing on the investigation of additional common susceptibility variants within established loci, rare genetic variants, non-coding variants, structural variations, epigenetic influences, epistatic interactions, pleiotropy effects, or other intricate mechanisms, deemed as significant determinants contributing to still-missing genetic components underlying these conditions.
In that sense, it would be helpful to discuss the genetic architecture as a continuum of complexities that underpins a spectrum of inheritance, ranging from monogenic to oligogenic as an intermediate construct, or polygenic architecture, and towards the omnigenic model capable of pinpointing the interconnected nature of biological networks. Furthermore, a comprehensive integration of multi-omics data is necessary to grasp the fundamental principles of neurobiological systemic frameworks in neurodegenerative diseases. These results could enhance our capability to predict and map contextually relevant molecular interactions contributing to endophenotype biology or shared mechanisms among neurodegenerative diseases.
We welcome submissions from researchers and clinicians related to the following topics, including but not limited to:
(1) How do rare and ultra-rare causative alleles, along with genetic interactions, explain the disease etiology and fraction of missing heritability?
(2) What is the impact of structural variations on the genetic architecture of neurodegenerative diseases – a hidden layer of genetic variation?
(3) What are the underlying factors that drive the complex genetic architecture of neurodegenerative diseases, including genetic modifiers, common familial and/or polygenic elements, and epigenetic alterations?
(4) Combining structural and functional multimodal neuroimaging datasets with genomic data offers a promising avenue to illustrate the systematic characterization of neurodegenerative pathologies.
(5) To what extent does the genetic background influence the earliest formation and propagation of pathological mechanisms that underpin a continuum between neurodegenerative diseases?
(6) The multi-omics characterization of patients creates an opportunity to develop new approaches for the classification of neurodegenerative diseases - multidimensional data integration.
(7) A more complete picture of polygenicity via network analysis of neurodegenerative disease can contribute to an integrative perspective on pathological changes.
Manuscripts must be submitted in accordance with the guidelines for Frontiers in Neurology. We look forward to receiving contributions that will improve our understanding of the genetic architecture of neurodegenerative diseases fostering progress in disease diagnosis, prevention, therapeutic interventions, and prognostic assessments.
Keywords: neurodegenerative diseases, genetic architecture, heritability, large-scale neuroimaging, genetic variation, structural variants, connectome, disease liability, omics, inherited epigenetic variation, cell-specific networks.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
