Case-control association mapping without cases

BioRxiv : the Preprint Server for Biology
Jimmy Z LiuJoseph K Pickrell


The case-control association study is a powerful method for identifying genetic variants that influence disease risk. However, the collection of cases can be time-consuming and expensive; in some situations it is more practical to identify family members of cases. We show that replacing cases with their first-degree relatives enables genome-wide association studies by proxy (GWAX). In randomly-ascertained cohorts, this approach enables previously infeasible studies of diseases that are rare in the cohort, and can increase power to detect association by up to 30% for diseases that are more common in the cohort. As an illustration, we performed GWAX of 12 common diseases in 116,196 individuals from the UK Biobank. By combining these results with published GWAS summary statistics in a meta-analysis, we replicated established risk loci and identified 17 newly associated risk loci: four in Alzheimer's disease, eight in coronary artery disease, and five in type 2 diabetes. In addition to informing disease biology, our results demonstrate the utility of association mapping using family history of disease as a phenotype to be mapped. We anticipate that this approach will prove useful in future genetic studies of complex traits in large...Continue Reading

Related Concepts

Genome-Wide Association Study
Diabetes Mellitus, Non-Insulin-Dependent
Meta-Analysis (Publications)
Meta Analysis (Statistical Procedure)
Coronary Artery Disease
Alzheimer's Disease
Coronary Arteriosclerosis
Genetic Studies
Case-Control Studies

Related Feeds

Alzheimer's Disease: Microglia (Preprints)

Microglial proliferation and activation, as well as its concentration around amyloid plaques, is a prominent feature of Alzheimer’s disease. Here is the latest research on microglia and Alzheimer’s disease.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Cardiovascular Inflammation

Inflammation plays a significant role in the development of cardiovascular diseases, an understanding of these endogenous processes is critical for evaluating the risks and potential treatment strategies. Discover the latest research on cardiovascular inflammation here.