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@ARTICLE{Dai:137578,
author = {J. Y. Dai and U. Peters and X. Wang and J. Kocarnik and J.
Chang-Claude$^*$ and M. L. Slattery and A. Chan and M.
Lemire and S. I. Berndt and G. Casey and M. Song and M. A.
Jenkins and H. Brenner$^*$ and A. P. Thrift and E. White and
L. Hsu},
title = {{D}iagnostics of {P}leiotropy in {M}endelian
{R}andomization {S}tudies: {G}lobal and {I}ndividual {T}ests
for {D}irect {E}ffects.},
journal = {American journal of epidemiology},
volume = {187},
issn = {1476-6256},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2018-01458},
pages = {2672-2680},
year = {2018},
abstract = {Diagnosing pleiotropy is critical for assessing the
validity of Mendelian randomization (MR) analyses. The
popular MR-Egger method evaluates whether there is evidence
of bias-generating pleiotropy among a set of candidate
genetic instrumental variables. In this article, we propose
GLIDE, GLobal and Individual tests for Direct Effects, a
statistical method to systematically evaluate pleiotropy
among the set of genetic variants, e.g., single nucleotide
polymorphisms (SNPs), used for MR. As a global test,
simulation experiments suggest that GLIDE is nearly
uniformly more powerful than the MR-Egger method. As a
sensitivity analysis, GLIDE is capable of detecting outliers
in individual variant-level pleiotropy, in order to obtain a
refined set of genetic instrumental variables. We used GLIDE
to analyze both body-mass index and height for risk of
colorectal cancer in the Genetics and Epidemiology of
Colorectal Cancer Consortium. Among the body mass index
associated SNPs and the height associated SNPs, several
individual variants showed evidence of pleiotropy. Removal
of these potentially pleiotropic SNPs resulted in
attenuation of respective estimates of the causal effects.
In summary, the proposed GLIDE method is useful for
sensitivity analyses and improves the validity of MR.},
cin = {C070 / G110 / C020},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)G110-20160331 /
I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30188971},
doi = {10.1093/aje/kwy177},
url = {https://inrepo02.dkfz.de/record/137578},
}