Genetic Epidemiology

Epidemiology is defined as the study of the distribution and determinants of diseases and events in populations. Genetic epidemiology is closely associated with traditional epidemiology, but focuses on the genetic determinants of disease and the joint effects of genes and nongenetic environmental factors on disease occurrence. In particular, the biological factors that underlie the action of genes and known mechanisms of inheritance are considered. Noteworthy is the way in which biology is factored into this research. In genetic epidemiology, this includes family pedigree studies, twin studies, studies of genetic polymorphisms, and other methods. Knowledge of genetics is important for understanding new medical developments and treatments for trauma exposures. All psychological traits, states, and outcomes have biological components.

Before information about DNA became available, scientists studying genetic variations associated with disease relied on Mendelian laws of inheritance. These principles implied a biological model for the sharing of genes between close relatives. If knowledge of this could be supplemented by a model for which a putatively causative genetic variant might lead to disease (e.g., two abnormal copies of gene G are required to cause disease X), etiological inferences could be drawn from the distribution of disease and phenotypic aggregation within families (termed segregation analysis). By incorporating the biology of gamete formation and chromosomal recombination into a mathematical model of the extent to which a given genetic marker is transmitted through a family in conjunction with a disease, epidemiologists have been able to estimate whether a causative genetic variant is likely to be associated with a specific genetic marker. This principle is the basis of genetic linkage analysis, which has achieved many breakthroughs in the recent past. With advances in genetic knowledge, this work continues to evolve.

Currently, extensive information about the human genome can now be included in many epidemiologic studies. Once it is known which versions of a potentially causative gene an individual possesses, looking for an association between variants in that gene and the disease of interest is fundamentally no different from observational “disease-exposure” studies in traditional epidemiology. There is also often no need to have an underlying biological model in these studies. But this does not mean that epidemiologists can ignore biology. Knowledge about the underlying biology, together with the inferential tools of modern epidemiology and biostatistics, allows important etiological questions to be answered in ways that are more rigorous than approaches that fail to use both epidemiologic and genetic methods.

Although many early successes have been with monogenic disorders, where familial recurrence seems to follow the laws of Mendelian inheritance, genetic epidemiology today is increasingly focused on complex diseases such as diabetes or mental disorders. The latter are typically caused by several (or more) interacting genetic and environmental components. The human genome is made up of deoxyribonucleic acid (DNA), which consists of a long sequence of nucleotide bases of four types: adenine (A), cytosine [Page 278](C), guanine (G), and thymine (T). Strong covalent bonds bind bases together along a single strand, and weaker hydrogen bonds pair A with T and C with G between the two strands. Under normal conditions, in the nucleus of a cell, DNA is double stranded. Double-stranded DNA is replicated by breakage of the two strands and construction of a new complementary strand for each, resulting in two identical copies of the original. A single strand of DNA can also act as a template for a complementary strand of ribonucleic acid (RNA). RNA is part of a group of nucleic acid molecules, which are some of the major macromolecules essential for life. Like DNA, RNA is made up of a long chain of component nucleotides. The sequence of nucleotides allows RNA to encode genetic information from DNA. This transcription RNA is similar to DNA. In certain regions of the DNA, transcribed RNA encodes instructions that tell the cell how to assemble amino acids to make proteins. Messenger RNA (mRNA) is then created by posttranscriptional processing to produce the codes for proteins. Proteins are the building blocks for life.

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