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Genetic association studies: Principles and applications

John Attia, MD, PhD, FRCPC, FRACP
Gordon Guyatt, MD
Section Editor
Benjamin A Raby, MD, MPH
Deputy Editor
Jennifer S Tirnauer, MD


Interest in the genetic determinants of disease originated with Gregor Mendel's observations on the genetics of the pea in the 1860s. Subsequent studies have identified many of the genes responsible for "Mendelian" diseases, conditions that follow a clear familial pattern. However, diseases inherited in a Mendelian fashion (eg, Huntington disease and cystic fibrosis) are rare.

More recently, the Human Genome Project has generated growing interest in genetic contribution to "complex" diseases. Such diseases combine some familial predisposition with a large environmental contribution. Examples include cardiovascular disease, diabetes, asthma, cancer, and obesity.

This topic will discuss the principles and clinical applications of genetic association studies in the elucidation of the genetic basis for common diseases with complex genetic components. Additional discussions of modes of inheritance and a glossary of genetic terms are presented separately. (See "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)" and "Principles of complex trait genetics" and "Genetics: Glossary of terms" and "Inheritance patterns of monogenic disorders (Mendelian and non-Mendelian)", section on 'Causes of non-Mendelian inheritance'.)


Genetic association studies — Genetic association studies are analogous to traditional epidemiologic association studies. Instead of seeking association between traditional risk variables (eg, hypertension) and disease outcomes (eg, stroke), a genetic association study looks for an association between a genetic variable and a specified condition.

Single nucleotide polymorphisms — The genetic variable most commonly studied is a single nucleotide polymorphism (SNP, pronounced "snip"). A SNP is a base pair change that occurs in at least 1 percent of the population. SNPs are not clearly deleterious, in contrast to mutations, which occur less frequently and generally have an adverse effect on protein function. (See "Overview of genetic variation".)

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Literature review current through: Nov 2017. | This topic last updated: Mar 24, 2017.
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