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 BMJ 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">Genetic disorder</span> Health problem caused by one or more abnormalities in the genome

A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development, or it can be inherited from two parents who are carriers of a faulty gene or from a parent with the disorder. When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA.

<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 incest only rarely.

<span class="mw-page-title-main">Tay–Sachs disease</span> Human medical condition

Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around the age of three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move, with death usually occurring by the age of three to five. Less commonly, the disease may occur later in childhood, adolescence, or adulthood. These forms tend to be less severe, but the juvenile form typically results in death by age 15.

Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be more linked than markers that are far apart. In other words, the nearer two genes are on a chromosome, the lower the chance of recombination between them, and the more likely they are to be inherited together. Markers on different chromosomes are perfectly unlinked, although the penetrance of potentially deleterious alleles may be influenced by the presence of other alleles, and these other alleles may be located on other chromosomes than that on which a particular potentially deleterious allele is located.

A heterozygote advantage describes the case in which the heterozygous genotype has a higher relative fitness than either the homozygous dominant or homozygous recessive genotype. Loci exhibiting heterozygote advantage are a small minority of loci. The specific case of heterozygote advantage due to a single locus is known as overdominance. Overdominance is a rare condition in genetics where the phenotype of the heterozygote lies outside of the phenotypical range of both homozygote parents, and heterozygous individuals have a higher fitness than homozygous individuals.

<span class="mw-page-title-main">Human behaviour genetics</span> Field that examines the role of genetic and environmental influences on human behaviour

Human behaviour genetics is an interdisciplinary subfield of behaviour genetics that studies the role of genetic and environmental influences on human behaviour. Classically, human behavioural geneticists have studied the inheritance of behavioural traits. The field was originally focused on determining the importance of genetic influences on human behaviour. It has evolved to address more complex questions such as: how important are genetic and/or environmental influences on various human behavioural traits; to what extent do the same genetic and/or environmental influences impact the overlap between human behavioural traits; how do genetic and/or environmental influences on behaviour change across development; and what environmental factors moderate the importance of genetic effects on human behaviour. The field is interdisciplinary, and draws from genetics, psychology, and statistics. Most recently, the field has moved into the area of statistical genetics, with many behavioural geneticists also involved in efforts to identify the specific genes involved in human behaviour, and to understand how the effects associated with these genes changes across time, and in conjunction with the environment.

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.

<span class="mw-page-title-main">Human genetics</span> Study of inheritance as it occurs in human beings

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">Medical genetics</span> Medicine focused on hereditary disorders

Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics.

<span class="mw-page-title-main">Neil Risch</span> American geneticist

Neil Risch is an American human geneticist and professor at the University of California, San Francisco (UCSF). Risch is the Lamond Family Foundation Distinguished Professor in Human Genetics, Founding Director of the Institute for Human Genetics, and Professor of Epidemiology and Biostatistics at UCSF. He specializes in statistical genetics, genetic epidemiology and population genetics.

Molecular epidemiology is a branch of epidemiology and medical science that focuses on the contribution of potential genetic and environmental risk factors, identified at the molecular level, to the etiology, distribution and prevention of disease within families and across populations. This field has emerged from the integration of molecular biology into traditional epidemiological research. Molecular epidemiology improves our understanding of the pathogenesis of disease by identifying specific pathways, molecules and genes that influence the risk of developing disease. More broadly, it seeks to establish understanding of how the interactions between genetic traits and environmental exposures result in disease.

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

Neurogenetics studies the role of genetics in the development and function of the nervous system. It considers neural characteristics as phenotypes, and is mainly based on the observation that the nervous systems of individuals, even of those belonging to the same species, may not be identical. As the name implies, it draws aspects from both the studies of neuroscience and genetics, focusing in particular how the genetic code an organism carries affects its expressed traits. Mutations in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological diseases, behavior and personality are all studied in the context of neurogenetics. The field of neurogenetics emerged in the mid to late 20th century with advances closely following advancements made in available technology. Currently, neurogenetics is the center of much research utilizing cutting edge techniques.

Cognitive genomics is the sub-field of genomics pertaining to cognitive function in which the genes and non-coding sequences of an organism's genome related to the health and activity of the brain are studied. By applying comparative genomics, the genomes of multiple species are compared in order to identify genetic and phenotypical differences between species. Observed phenotypical characteristics related to the neurological function include behavior, personality, neuroanatomy, and neuropathology. The theory behind cognitive genomics is based on elements of genetics, evolutionary biology, molecular biology, cognitive psychology, behavioral psychology, and neurophysiology.

<span class="mw-page-title-main">Health among the Amish</span> Health disorders within Amish communities

Health among the Amish is characterized by higher incidences of particular genetic disorders, especially among the Old Order Amish. These disorders include dwarfism, Angelman syndrome, and various metabolic disorders, such as Tay-Sachs disease, as well as an unusual distribution of blood types.

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.

Multifactorial diseases are not confined to any specific pattern of single gene inheritance and are likely to be caused when multiple genes come together along with the effects of environmental factors.

<span class="mw-page-title-main">Shih-Jen Hwang</span> Taiwanese-American biostatistician and epidemiologist

Shih-Jen Hwang is a Taiwanese-American biostatistician and epidemiologist. She is a staff scientist in the Laboratory for Cardiovascular Epidemiology and Genomics at the National Heart, Lung, and Blood Institute. She is an investigator on the Framingham Heart Study.

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". BMJ. 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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