RT Journal Article
SR Electronic
T1 Case-only exome sequencing and complex disease susceptibility gene discovery: study design considerations
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 10
OP 16
DO 10.1136/jmedgenet-2014-102697
VO 52
IS 1
A1 Lang Wu
A1 Daniel J Schaid
A1 Hugues Sicotte
A1 Eric D Wieben
A1 Hu Li
A1 Gloria M Petersen
YR 2015
UL http://jmg.bmj.com/content/52/1/10.abstract
AB Whole exome sequencing (WES) provides an unprecedented opportunity to identify the potential aetiological role of rare functional variants in human complex diseases. Large-scale collaborations have generated germline WES data on patients with a number of diseases, especially cancer, but less often on healthy controls under the same sequencing procedures. These data can be a valuable resource for identifying new disease susceptibility loci if study designs are appropriately applied. This review describes suggested strategies and technical considerations when focusing on case-only study designs that use WES data in complex disease scenarios. These include variant filtering based on frequency and functionality, gene prioritisation, interrogation of different data types and targeted sequencing validation. We propose that if case-only WES designs were applied in an appropriate manner, new susceptibility genes containing rare variants for human complex diseases can be detected.