Applied Genomics and Public Health

George P. Patrinos

• Publisher: Academic Press
• Year: 2019
• ISBN:
  9780128136966
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

Applied Genomics and Public Health examines the interdisciplinary and growing area of how evidence-based genomic knowledge can be applied to public health, population health, healthcare and health policies. The book gathers experts from a variety of disciplines, including life sciences, social sciences, and health care to develop a comprehensive overview of the field. In addition, the book delves into subjects such as pharmacogenomics, genethics, big data, data translation and analysis, economic evaluation, genomic awareness and education, sociology, pricing and reimbursement, policy measures and economic evaluation in genomic medicine. This book is essential reading for researchers and students exploring applications of genomics to population and public health. In addition, it is ideal for those in the biomedical sciences, medical sociologists, healthcare professionals, nurses, regulatory bodies and health economists interested in learning more about this growing field.

• Explores the growing application of genomics to population and public health
• Features internationally renowned contributors from a variety of related fields
• Contains chapters on important topics such as genomic data sharing, genethics and public health genomics, genomics and sociology, and regulatory aspects of genomic medicine and pharmacogenomics

Chapter 1

Applied Genomics and Public Health

George P. Patrinos^1,2,3, ¹Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Patras, Greece, ²Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates, ³Zayed Center of Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

Abstract

Personalized medicine aims to translate genomic findings into modern health care to inform medical decision-making and to individualize therapeutic interventions. The overall goal of personalized medicine is to improve the quality of life of the patients and, at the same time, reduce the overall cost of the health-care expenditure. While genomic discoveries are progressing at a very rapid pace, there have been much slower steps in the adjacent public health genomics disciplines, which would help catalyzing integration of these genomic discoveries into modern health care. This chapter provides an overview of the various public health genomics disciplines that are discussed in the various chapters in this textbook.

Keywords

Personalized medicine; applied genomics; public health; genome informatics; genomics awareness and education; ethical, legal, and societal issues; genetic counseling; emerging economies

Doctors have always recognized that every patient is unique, and doctors have always tried to tailor their treatments as best they can to individuals. You can match a blood transfusion to a blood type—that was an important discovery. What if matching a cancer cure to our genetic code was just as easy, just as standard? What if figuring out the right dose of medicine was as simple as taking our temperature?

–Former US President Barack H. Obama, January 30, 2015

1.1 Introduction

Personalized medicine exploits an individual’s genomic profile to support the clinical decision-making process and to individualize drug treatment modalities.¹ The concept of personalized medicine has gained momentum in the last decade; however, its founders have described the concept many centuries ago. Around 400 BCE, Hippocrates of Kos (460–370 BCE) stated, “… it is more important to know what kind of person suffers from a disease than to know the disease a person suffers.” Also, Ibn Sina (c. CE 980–1037) mentioned, “… in the make-up of most people there is somewhere a natural tendency to get out of order, some congenital weakness in one particular organ, tissue or system.” In particular, he termed this a “personal disposition” and put forward the view that each patient should be looked upon as a distinct and separate case. Interestingly, the Talmud (Yevamot 64b; 2nd century BCE) mentions that if a woman’s first two children had died from blood loss after circumcision, the third son should be excused from circumcision, hence indicating that the abnormal bleeding tendency was hereditary. These ancient statements and examples, if put together, may encapsulate the essence of modern, personalized, genomic medicine.

In recent years, significant advances have been made in understanding the genetic etiology of a wide range of human-inherited diseases. These advances have been made possible thanks to the significant breakthroughs and rapid pace of development of the genomic technology, aiding clinicians in their task of estimating disease risk as well as individualizing treatment modalities.²

Although there have been major leaps in genomics research and discovery work, facilitated by the genomic technology revolution,³ the pace of these discoveries has not met reciprocal advances in the translation of these findings into the clinic. In other words, there are often significant barriers that hamper the smooth incorporation of genomics research findings into daily medical practice, which have to do more with disciplines related to public health genomics rather than genomics research itself. These disciplines are of utmost importance since they contribute to the transition from genomics research to genomic and personalized medicine. These include ethical, legal, and societal aspects in genomics, also termed ELSI, genome informatics, improving and harmonizing the genetics education of health-care professionals and biomedical scientists, raising genetics awareness among the general public, and health economic evaluation in relation to genomic medicine. These disciplines can be exemplified as the supporting pillars that need to be erected, from the solid bedrock of genomics research, to firmly hold the superstructure of genomic and personalized medicine (Fig. 1.1). Presently, although the foundations of genomics research are becoming stronger with ever-increasing hopes and expectations, the pillars themselves are still largely under construction.⁴

Figure 1.1 Illustrative depiction of the transition of genomics research findings into personalized medicine interventions. Genomics research is metaphorically shown as the foundations of an ancient Greek temple. The rooftop of the temple depicts the various genomic and personalized medicine interventions. For the rooftop to hold, strong pillars need to be erected, each one representing the various public health disciplines, each one described in detail in the various chapters of this textbook (see also the text for details).

This textbook is a collection of timely contributions related to the various disciplines touching upon the implementation of genomic and personalized medicine and are closely related to public health genomics.

1.2 Genomics in Health Care

The contribution of germline gene variants to disease etiology is also known as genetic epidemiology. The genetic basis of several Mendelian diseases is elucidated through family-based studies and subsequent functional cloning. As highlighted in Chapter 2, From Genetic Epidemiology to Exposome and Systems Epidemiology, which describes this emerging discipline, although genome-wide association studies identified thousands of variants that are associated with complex genetic traits and conditions, the variants that are actually held responsible for these conditions largely remain undeciphered. As such, although genetic tests for high-penetrance gene variants have clinical utility for individuals, such as in preimplantation, prenatal, or postnatal diagnostics, and in preventive cascade screening of biological relatives (see also Chapter 10: Genetic Testing), genetic testing for complex phenotypes has utility only for research and public health rather than individual testing. Such complex phenotypes include rare diseases, cancer, cardiovascular and psychiatric diseases to name a few.

Rare diseases are defined by their prevalence and although individually infrequent, they affect almost half billion persons globally. Most of these rare diseases have a strong genetic component but till date, their underlying genetic etiology remains elusive. Chapter 3, Rare Diseases: Genomics and Public Health, summarizes the impact of genomic discoveries in accelerating clinical diagnosis, discoveries, and therapeutic interventions in rare diseases.

Of equal importance, cancer is one of the leading causes of death and a global public-health burden. Carcinogenesis originates from a cascade of tumor-promoting events, which result from a genomic-variant overload. Also, despite the emergence of new therapeutic modalities as the standard of care for several cancers, our ability to predict a patient’s response to these therapies, or the duration of these responses, is still lagging behind. Chapter 4, Applied Genomics and Public Health Cancer Genomics, addresses our current understanding of the contribution of various genetic aberrations and different regulatory pathways, genomics, and epigenomics in carcinogenesis and their impact in the era of precision medicine. This chapter also attempts to highlight how various genomics and integrated bioinformatics tools are being used to address many of the crucial questions in cancer medicine.

Similarly, psychiatric illnesses are also characterized by vast phenotypic heterogeneity, resulting from their underlying complex genetic basis, which largely remains unknown. The same is true for the genetic basis of interindividual differences in psychiatric drug-treatment response and toxicity, namely, for antipsychotics, antidepressants, and mood stabilizers. Chapter 5, Genomic Basis of Psychiatric Illnesses and Response to Psychiatric Drug Treatment Modalities, overviews psychiatric genomics and its implications for public health and care. It also attempts to highlight differences in psychiatric drug-treatment response and the genetic basis for the development of adverse drug reactions in these patients.

Chapter 6, Pharmacogenomics in Clinical Care: Implications for Public Health, goes a step further and attempts to summarize, more broadly, our current knowledge on the genomic etiology of variable drug treatment, both in terms of efficacy and also toxicity, namely, the development of adverse drug reactions. This chapter outlines the genetic basis of interindividual drug response for different medical specialties, namely, cardiology, oncology, psychiatry, neurology, and antiinfectious agents, and focuses on these drugs that are approved by the major regulatory bodies. Lastly, the chapter attempts to expand on the various applications of pharmacogenomics, in public health–related disciplines, in line with the overall aims of the textbook.

Monitoring an extended spectrum of agents, which has the potential of becoming pathogenic and virulent, is of major concern in public health. Also, new microbiota has emerged, requiring them to be included in the mainstream monitoring and surveillance practice to prevent more aggressive outbreaks. Chapter 7, Microbial Genomics in Public Health: A Translational Risk-Response Aspect, touches upon microbiomics and related applications including genomic-related approaches for adaptive and massive testing.

All the aforementioned genomics approaches yield a huge amount of data that need to be processed for them to be correlated with the underlying phenotype. In particular, genome-wide association studies and next generation–sequencing approaches rely on big-data analysis and hence, bioinformatics plays a vital role in the analysis and interpretation of these genomic data.⁵ Chapter 8, Genome Informatics Pipelines and Genome Browsers, attempts to summarize the various bioinformatics pipelines used in translational research and figure out how these data, from the genomic analysis at the level of individuals or populations, can be gradually integrated into the therapeutic and preventative guidelines of modern health-care systems. The chapter also addresses the various computational barriers and challenges, which arise from analyzing massive volumes of genetic data, such as annotation and quantitative data and read alignments. Similarly, genome informatics and genomic data analysis rely on the development and expert curation of genomic databases and translational tools that convert genomics data, which are often difficult to be understood by the treating physicians, to a clinically meaningful format. Chapter 9, Translational Tools and Databases in Genomic Medicine, provides an update on the main genomics databases that are developed to accommodate and curate the huge volume of data resulting from biomarker discovery and next generation–sequencing analysis. It also touches upon the translational tools that facilitate the practice of pharmacogenomics and personalized medicine for pharmacogenomic data interpretation.

As mentioned previously, there are several genetic tests with clinical utility in preimplantation, prenatal, postnatal, and even preventive molecular diagnostics, which resulted from genetic epidemiology and genome-wide association studies, and are developed for high-penetrance gene variants.⁶ Chapter 10, Genetic Testing, provides an overview on the various aspects of molecular diagnostics, the main types of genetic tests, their advantages and limitations, and their usefulness in personalized medicine, clinical practice, and disease diagnosis.

1.3 Personalized Medicine and Public Health

As mentioned earlier, the smooth incorporation of the genomic discoveries into modern medical practices relies on addressing a number of obstacles, one of which is the incomplete mapping of the key stakeholders involved in this translation process, namely, the major players, their power of intervention and policy positions, their interests and networks, and coalitions that connect them. Also, such comprehensive mapping should be complemented with the proper understanding of the policies, opinions, and overall policy content. Chapter 11, Assessing the Stakeholder Landscape and Stance Point on Genomic and Personalized Medicine, aims to provide an overview of the process for assessing the views and opinions of stakeholders toward personalized medicine and an example of implementing such an approach in a health-care environment, so that adoption of genomics into the mainstream medical interventions is expedited.

Also, a crucial bottleneck that requires rectification is the poor genomics education and literacy among health-care professionals and biomedical scientists. Chapter 12, Health-Care Professionals’ Awareness and Understanding of Genomics, critically examines the le...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Chapter 1. Applied Genomics and Public Health
• Part I: Genomics in Healthcare
• Part II: Personalised Medicine and Public Health
• Index