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@INPROCEEDINGS{Vaitsiakhovich:145229,
author = {Vaitsiakhovich, Tatsiana and Becker, Tim},
title = {{M}eta-{A}nalysis of {M}ultiple {R}egression {M}odels in
{G}enome-{W}ide {A}ssociation {S}tudies},
reportid = {DZNE-2020-00587},
year = {2015},
abstract = {Meta-analysis refers to the statistical synthesis of the
results from a series of related studies. Meta-analysis of
summary statistics from Genome-wide association studies
(GWAS) may lead to dis-covery of new susceptibility loci
without the need to exchange gen-otype data.Well-known
p-value combination methods can be applied to an arbitrary
association test. However, these methods do not pro-vide
summary effects and are known to be underpowered for
high-dimensional models. The broadly used methods for
meta-analysis of individual GWAS results address mostly one
parameter models. Results of multiple regression analysis
applied, for instance, to ge-nome-wide interaction analysis
have rarely been used due to the complexities underlying the
process of their synthesis. For high-dimensional models the
gain of power can be achieved when meta-analysis methods
incorporate information on study-specific properties of
parameter estimates, their effect directions, standard
errors and covariance structure. In this context, a method
for the synthesis of regression slopes (MSRS) represents a
perspec-tive approach of meta-analysis for advanced GWAS.
MSRS pro-vides meta-analysis p-values and common parameter
estimates of multiple regression models for an arbitrary
number of parameters, and can be used to test the
homogeneity of studies results. We introduce an efficient,
powerful and freely available soft-ware tool METAINTER,
which implements MSRS and three fur-ther meta-analysis
methods: Fisher’s method, Stouffer’s method with weights
and Stouffer’s method with weights and effect direc-tions.
METAINTER enables meta-analysis of tests for and under
gene-gene interaction, single-SNP association tests with
several degrees of freedom, global haplotype tests etc.
Simulation study shows that MSRS has correct type I error
and its power comes close to that of the joint sample
analysis. We have conducted a real data analysis of six GWAS
of type 2 Diabetes. For each study, a genome-wide
interaction analysis of all SNP pairs has been performed by
logistic regression tests. The results have then been
meta-analysed with METAINTER.},
month = {Apr},
date = {2015-04-16},
organization = {43rd European Mathematical Genetics
Meeting, Brest (France), 16 Apr 2015 -
17 Apr 2015},
cin = {AG Becker},
cid = {I:(DE-2719)1013007},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)1},
url = {https://pub.dzne.de/record/145229},
}