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Mendelian Randomization using Public Data from Genetic Consortia

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journal contribution
posted on 20.09.2016, 15:31 by John R. Thompson, Cosetta Minelli, Fabiola Del Greco M
Mendelian randomization (MR) is a technique that seeks to establish causation between an exposure and an outcome using observational data. It is an instrumental variable analysis in which genetic variants are used as the instruments. Many consortia have meta-analysed genome-wide associations between variants and specific traits and made their results publicly available. Using such data, it is possible to derive genetic risk scores for one trait and to deduce the association of that same risk score with a second trait. The properties of this approach are investigated by simulation and by evaluating the potentially causal effect of birth weight on adult glucose level. In such analyses, it is important to decide whether one is interested in the risk score based on a set of estimated regression coefficients or the score based on the true underlying coefficients. MR is primarily concerned with the latter. Methods designed for the former question will under-estimate the variance if used for MR. This variance can be corrected but it needs to be done with care to avoid introducing bias. MR based on public data sources is useful and easy to perform, but care must be taken to avoid false precision or bias.

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Citation

The international journal of biostatistics, 2016, DOI: 10.1515/ijb-2015-0074

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Health Sciences

Version

VoR (Version of Record)

Published in

The international journal of biostatistics

Publisher

De Gruyter

issn

1557-4679

Acceptance date

19/04/2016

Copyright date

2016

Available date

19/04/2017

Publisher version

http://www.degruyter.com/view/j/ijb.ahead-of-print/ijb-2015-0074/ijb-2015-0074.xml

Language

en

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