Rare-variant collapsing analyses for complex traits: guidelines and applications.

2019-10-11

Povysil, Gundula

Petrovski, Slavé

Hostyk, Joseph

Aggarwal, Vimla

Allen, Andrew S

Goldstein, David B

Journal Article

0000-0002-1527-961X

0000-0001-7016-7218

0000-0002-1111-2820

10.1038/s41576-019-0177-4

The first phase of genome-wide association studies (GWAS) assessed the role of common variation in human disease. Advances optimizing and economizing high-throughput sequencing have enabled a second phase of association studies that assess the contribution of rare variation to complex disease in all protein-coding genes. Unlike the early microarray-based studies, sequencing-based studies catalogue the full range of genetic variation, including the evolutionarily youngest forms. Although the experience with common variants helped establish relevant standards for genome-wide studies, the analysis of rare variation introduces several challenges that require novel analysis approaches.

link

Nature reviews. Genetics 2019; 20(12): 747-759

Nature reviews. Genetics