TY - JOUR
T1 - Case-only exome sequencing and complex disease susceptibility gene discovery
T2 - Study design considerations
AU - Wu, Lang
AU - Schaid, Daniel J.
AU - Sicotte, Hugues
AU - Wieben, Eric D.
AU - Li, Hu
AU - Petersen, Gloria M.
PY - 2015
Y1 - 2015
N2 - 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.
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.
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U2 - 10.1136/jmedgenet-2014-102697
DO - 10.1136/jmedgenet-2014-102697
M3 - Review article
C2 - 25371537
AN - SCOPUS:84961289502
SN - 0022-2593
VL - 52
SP - 10
EP - 16
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 1
ER -