title: How to use an article about genetic association: A: Background concepts.
abstract: This is the first in a series of 3 articles serving as an introduction to clinicians wishing to read and critically appraise genetic association studies. We summarize the key concepts in genetics that clinicians must understand to review these studies, including the structure of DNA, transcription and translation, patterns of inheritance, Hardy-Weinberg equilibrium, and linkage disequilibrium. We review the types of DNA variation, including single-nucleotide polymorphisms (SNPs), insertions, and deletions, and how these can affect protein function. We introduce the idea of genetic association for both single-candidate gene and genome-wide association studies, in which thousands of genetic variants are tested for association with disease. We use the APOE polymorphism and its association with dementia as a case study to demonstrate the concepts and introduce the terminology used in this field. The second and third articles will focus on issues of validity and applicability.
authors.affiliation: Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Hunter Medical Research Institute, and Department of General Medicine, John Hunter Hospital, Newcastle, Australia. john.attia@newcastle.edu.au
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: Ammarin
authors.initials: A
authors.lastname: Thakkinstian
authors.forename: Mark
authors.initials: M
authors.lastname: McEvoy
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Cosetta
authors.initials: C
authors.lastname: Minelli
authors.forename: John
authors.initials: J
authors.lastname: Thompson
authors.forename: Claire
authors.initials: C
authors.lastname: Infante-Rivard
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
mesh_terms: D004247:DNA; D008040:Genetic Linkage; D014644:Genetic Variation; D005826:Genetics, Medical; D006801:Humans; D040582:Inheritance Patterns; D010506:Periodicals as Topic; D012196:Review Literature as Topic; D009626:Terminology as Topic
chemical_list: D004247:DNA