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.

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". It is closely allied to both molecular epidemiology and statistical genetics, but these overlapping fields each have distinct emphases, societies and journals. One definition of the field closely follows that of

behavior genetics 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" ...

, 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". 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."

History

As early as the 4th century BC,

Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...

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.

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

Fundamentals

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

Familial aggregation Family aggregation, also known as familial aggregation, is the clustering of certain traits, behaviours, or disorders within a given family. Family aggregation may arise because of genetic or environmental similarities.Butcher, J., S. Mineka, and ...

studies: Is there a genetic component to the disease, and what are the relative contributions of genes and environment? * Segregation studies: What is the pattern of inheritance of the disease (e.g. dominant or recessive)? * Linkage studies: On which part of which

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...

is the disease gene located? * Association studies: Which

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chrom ...

of which gene is associated with the disease? 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 disorder 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 disorde ...

s). This has developed rapidly in the first decade of the 21st century following completion of the

Human Genome Project The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both ...

, 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 polymorphism A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to ge ...

s 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 Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genet ...

. 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.

Approaches

Genetic epidemiological research follows 3 discreet steps, as outlined by M.Tevfik Dorak: # Establishing that there is a genetic component to the disorder. # 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). # Identifying the gene(s) responsible for the genetic component. These research methodologies can be assessed through either family or population studies.

References

External links

''Genetic Epidemiology'' (journal)International Genetic Epidemiology Society
{{DEFAULTSORT:Genetic Epidemiology Human genetics Personalized medicine