UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Adjustment for index event bias in genome-wide association studies of subsequent events

Dudbridge, F; Allen, RJ; Sheehan, NA; Schmidt, AF; Lee, JC; Jenkins, RG; Wain, LV; ... Patel, RS; + view all (2019) Adjustment for index event bias in genome-wide association studies of subsequent events. Nature Communications , 10 , Article 1561. 10.1038/s41467-019-09381-w. Green open access

[thumbnail of s41467-019-09381-w.pdf]
Preview
Text
s41467-019-09381-w.pdf - Published version

Download (700kB) | Preview

Abstract

Following numerous genome-wide association studies of disease susceptibility, there is increasing interest in genetic associations with prognosis, survival or other subsequent events. Such associations are vulnerable to index event bias, by which selection of subjects according to disease status creates biased associations if common causes of incidence and prognosis are not accounted for. We propose an adjustment for index event bias using the residuals from the regression of genetic effects on prognosis on genetic effects on incidence. Our approach eliminates this bias when direct genetic effects on incidence and prognosis are independent, and otherwise reduces bias in realistic situations. In a study of idiopathic pulmonary fibrosis, we reverse a paradoxical association of the strong susceptibility gene MUC5B with increased survival, suggesting instead a significant association with decreased survival. In re-analysis of a study of Crohn’s disease prognosis, four regions remain associated at genome-wide significance but with increased standard errors.

Type: Article
Title: Adjustment for index event bias in genome-wide association studies of subsequent events
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-019-09381-w
Publisher version: https://doi.org/10.1038/s41467-019-09381-w
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10073001
Downloads since deposit
47Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item