Case-only exome sequencing and complex disease susceptibility gene discovery: Study design considerations

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10-16
Number of pages7
JournalJournal of Medical Genetics
Volume52
Issue number1
DOIs
StatePublished - 2015

Fingerprint

Exome
Disease Susceptibility
Genetic Association Studies
Gene Frequency
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Medicine(all)

Cite this

@article{8cf307532f88445b8eaee0eb215d4853,
title = "Case-only exome sequencing and complex disease susceptibility gene discovery: Study design considerations",
abstract = "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.",
author = "Lang Wu and Schaid, {Daniel J} and Hugues Sicotte and Wieben, {Eric D} and Hu Li and Petersen, {Gloria M}",
year = "2015",
doi = "10.1136/jmedgenet-2014-102697",
language = "English (US)",
volume = "52",
pages = "10--16",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "1",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84961289502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961289502&partnerID=8YFLogxK

U2 - 10.1136/jmedgenet-2014-102697

DO - 10.1136/jmedgenet-2014-102697

M3 - Review article

C2 - 25371537

AN - SCOPUS:84961289502

VL - 52

SP - 10

EP - 16

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 1

ER -