Genetic epidemiology

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Genetic epidemiology is the study of the role of genetic factors in determining health and disease in families and in populations, and the interplay of such genetic factors with environmental factors. Genetic epidemiology seeks to derive a statistical and quantitative analysis of how genetics work in large groups. [1]

Contents

Definition

The use of the term Genetic epidemiology emerged in the mid-1980s as a new scientific field.

In formal language, genetic epidemiology was defined by Newton Morton, one of the pioneers of the field, as "a science which deals with the etiology, distribution, and control of disease in groups of relatives and with inherited causes of disease in populations". [2] It is closely allied to both molecular epidemiology and statistical genetics, but these overlapping fields each have distinct emphases, societies and journals. [1]

One definition of the field closely follows that of behavior genetics, defining genetic epidemiology as "the scientific discipline that deals with the analysis of the familial distribution of traits, with a view to understanding any possible genetic basis", and that "seeks to understand both the genetic and environmental factors and how they interact to produce various diseases and traits in humans". [3] The British Medical Journal adopts a similar definition, "Genetic epidemiology is the study of the aetiology, distribution, and control of disease in groups of relatives and of inherited causes of disease in populations." [4]

History

As early as the 4th century BC, Hippocrates suggested in his essay "On Airs, Waters, and Places" that factors such as behavior and environment may play a role in disease. Epidemiology entered a more systematic phase with the work of John Graunt, who in 1662 tried to quantify mortality in London using a statistical approach, tabulating various factors he thought played a role in mortality rates. John Snow is considered to be the father of epidemiology, and was the first to use statistics to discover and target the cause of disease, specifically of cholera outbreaks in 1854 in London. He investigated the cases of cholera and plotted them onto a map identifying the most likely cause of cholera, which was shown to be contaminated water wells.[ citation needed ]

Modern history

Modern genetics began on the foundation of Gregor Mendel's work. Once this became widely known, it spurred a revolution in studies of hereditary throughout the animal kingdom; with studies showing genetic transmission and control over characteristics and traits. As gene variation was shown to affect disease, work began on quantifying factors affecting disease, accelerating in the 20th century. The period since the second world war saw the greatest advancement of the field, with scientists such as Newton Morton helping form the field of genetic epidemiology as it is known today, with the application of modern genetics to the statistical study of disease, as well as the establishment of large-scale epidemiological studies such as the Framingham Heart Study. [5]

In the 1960s and 1970s, epidemiology played a part in strategies for the worldwide eradication of naturally occurring smallpox. [6]

Fundamentals

Traditionally, the study of the role of genetics in disease progresses through the following study designs, each answering a slightly different question: [7]

This traditional approach has proved highly successful in identifying monogenic disorders and locating the genes responsible.

More recently, the scope of genetic epidemiology has expanded to include common diseases for which many genes each make a smaller contribution (polygenic, multifactorial or multigenic disorders). This has developed rapidly in the first decade of the 21st century following completion of the Human Genome Project, as advances in genotyping technology and associated reductions in cost has made it feasible to conduct large-scale genome-wide association studies that genotype many thousands of single nucleotide polymorphisms in thousands of individuals. These have led to the discovery of many genetic polymorphisms that influence the risk of developing many common diseases. The genetic epidemiology can also be skewed by the presence of evolutionary pressures that induce negative selection during molecular evolution. This negative selection can be determined by tracking the skewness of the distribution of mutations with putatively severe effects as compared to the distribution of mutations with putatively mild or absent effect. [8]

Approaches

Genetic epidemiological research follows 3 discrete steps, as outlined by M.Tevfik Dorak:

  1. Establishing that there is a genetic component to the disorder.
  2. Establishing the relative size of that genetic effect in relation to other sources of variation in disease risk (environmental effects such as intrauterine environment, physical and chemical effects as well as behavioral and social aspects).
  3. Identifying the gene(s) responsible for the genetic component.

These research methodologies can be assessed through either family or population studies. [9]

See also

Related Research Articles

<span class="mw-page-title-main">Genetics</span> Science of genes, heredity, and variation in living organisms

Genetics is the study of genes, genetic variation, and heredity in organisms. It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.

<span class="mw-page-title-main">Mutation</span> Alteration in the nucleotide sequence of a genome

In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from substitution, insertion or deletion of segments of DNA due to mobile genetic elements.

<span class="mw-page-title-main">Inbreeding</span> Reproduction by closely related organisms

Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically. By analogy, the term is used in human reproduction, but more commonly refers to the genetic disorders and other consequences that may arise from expression of deleterious recessive traits resulting from incestuous sexual relationships and consanguinity. Animals avoid inbreeding only rarely.

<span class="mw-page-title-main">Single-nucleotide polymorphism</span> Single nucleotide in genomic DNA at which different sequence alternatives exist

In genetics and bioinformatics, a single-nucleotide polymorphism is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently large fraction of the population, many publications do not apply such a frequency threshold.

A quantitative trait locus (QTL) is a locus that correlates with variation of a quantitative trait in the phenotype of a population of organisms. QTLs are mapped by identifying which molecular markers correlate with an observed trait. This is often an early step in identifying the actual genes that cause the trait variation.

Forward genetics is a molecular genetics approach of determining the genetic basis responsible for a phenotype. Forward genetics provides an unbiased approach because it relies heavily on identifying the genes or genetic factors that cause a particular phenotype or trait of interest.

Human genetics is the study of inheritance as it occurs in human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, population genetics, developmental genetics, clinical genetics, and genetic counseling.

Statistical genetics is a scientific field concerned with the development and application of statistical methods for drawing inferences from genetic data. The term is most commonly used in the context of human genetics. Research in statistical genetics generally involves developing theory or methodology to support research in one of three related areas:

<span class="mw-page-title-main">Gene–environment interaction</span> Response to the same environmental variation differently by different genotypes

Gene–environment interaction is when two different genotypes respond to environmental variation in different ways. A norm of reaction is a graph that shows the relationship between genes and environmental factors when phenotypic differences are continuous. They can help illustrate GxE interactions. When the norm of reaction is not parallel, as shown in the figure below, there is a gene by environment interaction. This indicates that each genotype responds to environmental variation in a different way. Environmental variation can be physical, chemical, biological, behavior patterns or life events.

<span class="mw-page-title-main">Genetic analysis</span>

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<span class="mw-page-title-main">Neurogenetics</span> Study of role of genetics in the nervous system

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Behavioural genetics, also referred to as behaviour genetics, is a field of scientific research that uses genetic methods to investigate the nature and origins of individual differences in behaviour. While the name "behavioural genetics" connotes a focus on genetic influences, the field broadly investigates the extent to which genetic and environmental factors influence individual differences, and the development of research designs that can remove the confounding of genes and environment. Behavioural genetics was founded as a scientific discipline by Francis Galton in the late 19th century, only to be discredited through association with eugenics movements before and during World War II. In the latter half of the 20th century, the field saw renewed prominence with research on inheritance of behaviour and mental illness in humans, as well as research on genetically informative model organisms through selective breeding and crosses. In the late 20th and early 21st centuries, technological advances in molecular genetics made it possible to measure and modify the genome directly. This led to major advances in model organism research and in human studies, leading to new scientific discoveries.

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<span class="mw-page-title-main">Complex traits</span>

Complex traits are phenotypes that are controlled by two or more genes and do not follow Mendel's Law of Dominance. They may have a range of expression which is typically continuous. Both environmental and genetic factors often impact the variation in expression. Human height is a continuous trait meaning that there is a wide range of heights. There are an estimated 50 genes that affect the height of a human. Environmental factors, like nutrition, also play a role in a human's height. Other examples of complex traits include: crop yield, plant color, and many diseases including diabetes and Parkinson's disease. One major goal of genetic research today is to better understand the molecular mechanisms through which genetic variants act to influence complex traits. Complex traits are also known as polygenic traits and multigenic traits.

Muin Joseph Khoury is an American geneticist and epidemiologist who conducts research in the field of public health genomics. He is the founding director of the Office of Public Health Genomics at the Centers for Disease Control and Prevention since 1997. He has also been a senior advisor in public health genomics at the National Cancer Institute since 2007.

References

  1. 1 2 Khoury, Muin J.; Beaty, Terri H.; Cohen, Bernice H. (1993-01-01). Fundamentals of Genetic Epidemiology. Oxford University Press. ISBN   9780195052886.
  2. ↑ Morton, N. E. (1982). Outline of Genetic Epidemiology. New York: Karger. ISBN   978-3-8055-2269-4.
  3. ↑ "Genetic Epidemiology Defined". www.biostat.wustl.edu. Archived from the original on 2015-07-22. Retrieved 2016-02-07.
  4. ↑ Kaprio, Jaakko (2000-05-06). "Genetic epidemiology". British Medical Journal . 320 (7244): 1257–1259. doi:10.1136/bmj.320.7244.1257. ISSN   0959-8138. PMC   1117994 . PMID   10797040.
  5. ↑ Principles of Epidemiology in Public Health Practice - An Introduction to Applied Epidemiology and Biostatistics. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. 2006. pp. 1, 7–12.
  6. ↑ Henderson, D. A. (1972-03-20). "Epidemiology in the Global Eradication of Smallpox". International Journal of Epidemiology. 1 (1): 25–30. doi:10.1093/ije/1.1.25. ISSN   0300-5771. PMID   4669176.
  7. ↑ M. Tevfik Dorak (2008-03-03). "Introduction to Genetic Epidemiology" . Retrieved 2008-03-04.
  8. ↑ Simcikova D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC   6901466 . PMID   31819097.
  9. ↑ "INTRODUCTION TO GENETIC EPIDEMIOLOGY [M.Tevfik DORAK]". www.dorak.info. Retrieved 2016-02-07.

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