The development of genome-wide association studies and their application to complex diseases, including lupus

• Published in: Lupus Vol. 22; no. 12; pp. 1205 - 1213
• Main Authors: Bentham, J, Vyse, TJ
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.10.2013; Sage Publications Ltd
• Subjects: Arthritis, Rheumatoid - genetics; Cardiovascular disease; Coronary Disease - genetics; Coronary heart disease; Diabetes Mellitus, Type 1 - genetics; Genes; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Humans; Hypotheses; Lupus; Lupus Erythematosus, Systemic - genetics; Medical research; Research Design; United Kingdom > UK; renal lupus; cardiovascular disease; Systemic lupus erythematosus
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203313492870

In this review, we explain the motivation for carrying out genome-wide association studies (GWAS), contrasting the achievements of linkage-based experiments for Mendelian traits with the difficulties found when applying that type of experiment to complex diseases. We explain the technical and organizational developments that were required to make GWAS feasible, as well as some of the theoretical concerns that were raised during the design of these studies. We describe the impressive achievements of GWAS in lupus, and compare them with the experiences in three other genetically complex disorders: rheumatoid arthritis, type 1 diabetes and coronary heart disease. GWAS have been successful in identifying many new susceptibility loci for these four diseases, and have provided the motivation for novel immunological work. We conclude by describing preliminary steps that have been taken towards translating the results of GWAS into improvements in patient care, explaining some of the difficulties involved, as well as successes that have already been achieved.