Variability of transposable elements in six genetic isolates from North-Eastern Italy and their relationship with alcohol consumption, tobacco use and BMI – BMC Genomics

Genomic Variation, Transposable Elements, and Human Health: A Framework for Achieving Sustainable Development Goals

1.0 Introduction: Aligning Genomic Research with Global Sustainability

Understanding human genetic variation is paramount for advancing global public health and achieving the United Nations Sustainable Development Goals (SDGs). This report synthesizes findings from population genetics, with a particular focus on transposable elements (TEs), to illustrate the critical link between genomic research and sustainable development. The primary focus is on SDG 3: Good Health and Well-being, which aims to ensure healthy lives and promote well-being for all at all ages. Furthermore, this research supports SDG 10: Reduced Inequalities by ensuring that genomic medicine is inclusive of diverse populations, and SDG 17: Partnerships for the Goals through the collaborative nature of large-scale genomic studies.

2.0 Population Genetics and Health Equity

The study of isolated and diverse populations, such as those along the Italian Peninsula, provides crucial insights into the interplay of evolutionary forces and disease susceptibility. This knowledge is fundamental to developing equitable health strategies.

2.1 Insights from Population Isolates

• Analysis of Italian populations reveals a complex genomic background shaped by both neutral and adaptive evolution, which influences differential disease susceptibility. This underscores the need for population-specific health interventions to meet the targets of SDG 3.
• Whole-genome sequencing of isolated European populations has identified an enrichment of low-frequency functional variants, which are critical for understanding medically relevant complex traits and contributes to the goal of reducing premature mortality from non-communicable diseases (SDG 3.4).
• Geographic and linguistic factors have been shown to shape human biodiversity, highlighting the importance of studying diverse groups to reduce health inequalities (SDG 10).

2.2 Methodological Advancements and Global Collaboration

The progress in this field relies on robust analytical tools and global partnerships, reflecting the spirit of SDG 17.

1. Large-Scale Projects: Initiatives like the 1000 Genomes Project provide a global reference for human genetic variation, enabling comprehensive research worldwide.
2. Analytical Tools: Software such as PLINK, ADMIXTURE, and MELT allows for population-scale discovery and analysis of genetic markers, including mobile element insertions.
3. Association Studies: Genome-wide association studies (GWAS) are essential for identifying genetic loci associated with complex diseases and behaviors, directly informing public health policies.

3.0 The Role of Transposable Elements in Health and Disease

Transposable elements (TEs), including Alu, L1, and SVA retrotransposons, are mobile DNA sequences that constitute a significant portion of the human genome. While once considered “junk DNA,” they are now recognized as key players in genome evolution, gene regulation, and human disease, making their study essential for achieving SDG 3.

3.1 TEs as Drivers of Genetic Disease

TE insertions can disrupt gene function and are implicated in numerous genetic disorders. Understanding these mechanisms is vital for diagnosis and treatment.

• Monogenic Diseases: De novo insertions of TEs have been identified as the cause of diseases such as Haemophilia A and B, demonstrating a novel mechanism for mutation in humans.
• Complex Diseases: TEs are linked to a range of complex conditions, including cancer, neurological disorders, and familial hypercholesterolemia. Research into their deregulation is crucial for developing targeted therapies.
• Gene Regulation: TEs can influence host gene expression, alternative splicing, and transcription, contributing to the “missing heritability” of complex diseases and providing new avenues for therapeutic intervention.

3.2 TEs and Substance Use Disorders

Investigating the genetic underpinnings of behavioral traits and substance use is central to SDG 3.5: “Strengthen the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol.”

• Behavioral Traits: Genetic studies have identified loci associated with risk tolerance, risky behaviors, and behavioral disinhibition, which are often comorbid with substance use disorders.
• Addiction and Dependence: Genome-wide studies have revealed novel risk genes for the progression from initial cocaine or opioid use to dependence. The role of TEs in modulating neuropeptide gene expression and their involvement in the central nervous system suggests a potential link to addiction pathways.
• Alcohol and Tobacco Use: The genetic diversity across populations fuels gene discovery for tobacco and alcohol use, highlighting the need for inclusive research to create effective, global public health strategies against harmful substance use.

4.0 Conclusion: A Genomic Roadmap for Sustainable Development

The synthesis of research on population genetics and transposable elements provides a powerful framework for addressing global health challenges. By elucidating the genetic basis of disease and behavior, this field directly contributes to the targets of SDG 3 (Good Health and Well-being) and SDG 10 (Reduced Inequalities). The collaborative, data-intensive nature of this work exemplifies SDG 17 (Partnerships for the Goals). Continued investment in genomic research is not merely a scientific endeavor but a strategic imperative for building a healthier, more equitable, and sustainable future for all.

Analysis of Sustainable Development Goals (SDGs) in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

Based on the titles of the scientific papers listed in the article’s references, the primary Sustainable Development Goal (SDG) addressed is:

• SDG 3: Good Health and Well-being

Explanation:

A significant number of the cited research papers focus on human genetics, disease susceptibility, specific medical conditions, mental health disorders, and substance abuse. These topics are central to the mission of SDG 3, which aims to ensure healthy lives and promote well-being for all at all ages.

2. What specific targets under those SDGs can be identified based on the article’s content?

Within SDG 3, the following specific targets are relevant to the issues discussed in the referenced papers:

1. Target 3.4: Reduce by one-third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.

   • Explanation: The article references numerous studies on non-communicable diseases (NCDs) and mental health. This indicates a focus on understanding the genetic and biological basis of these conditions, which is a foundational step for prevention and treatment.
     • Research on “disease susceptibility” (Ref 1), “human cancer” (Ref 19), “Haemophilia” (Ref 21, 22), “familial hypercholesterolemia” (Ref 24), and “Alzheimer’s disease” (Ref 60) directly relates to NCDs.
     • Studies concerning “diseases of the central nervous system” (Ref 25), “posttraumatic stress disorder” (Ref 29), “schizophrenia” (Ref 59), and “anxiety disorders” (Ref 61) align with the target’s goal of promoting mental health and well-being.

2. Target 3.5: Strengthen the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol.

   • Explanation: Several references point to research on the genetic factors underlying substance use and dependence. This research is crucial for developing targeted prevention and treatment strategies.
     • Papers mentioning “alcohol use disorders” (Ref 30), “alcoholism” (Ref 31), “Tobacco and nicotine use” (Ref 32, 56), and “cocaine or opioid use to dependence” (Ref 58, 63) are directly connected to this target.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

The article, being a list of references, does not explicitly state any quantitative indicators. However, the topics of the cited research papers imply the importance of certain health indicators for measuring progress.

1. Indicators related to Target 3.4 (Non-communicable diseases and mental health):

   • Implied Indicator: Prevalence and incidence of specific non-communicable and genetic diseases.
     • Explanation: The focus of studies on conditions like “human cancer” (Ref 19), “Haemophilia” (Ref 21, 22), “hypercholesterolemia” (Ref 24), and “Alzheimer’s disease” (Ref 60) implies that the prevalence of these diseases is a key metric of public health concern. Research into their genetic basis aims to provide tools to eventually reduce this prevalence.
   • Implied Indicator: Prevalence of mental and neurological disorders.
     • Explanation: The existence of genome-wide association studies for “schizophrenia” (Ref 59), “anxiety disorders” (Ref 61), and research on “posttraumatic stress disorder” (Ref 29) suggests that the prevalence of these mental health conditions is a critical area of focus. Measuring changes in their prevalence would be an indicator of progress.

2. Indicators related to Target 3.5 (Substance abuse):

   • Implied Indicator: Prevalence of substance use disorders.
     • Explanation: The numerous studies on “alcohol use disorders” (Ref 30), “tobacco and alcohol use” (Ref 56), and “cocaine or opioid use to dependence” (Ref 58) imply that the rate of substance abuse and dependence in the population is the primary measure of the problem. Tracking these rates is essential to evaluating the effectiveness of prevention and treatment efforts.

4. Table of Findings

Source: bmcgenomics.biomedcentral.com