% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Meesters:136657,
author = {Meesters, Christian and Leber, Markus and Herold, Christine
and Angisch, Marina and Mattheisen, Manuel and Drichel,
Dmitriy and Lacour, André and Becker, Tim},
title = {{Q}uick, 'imputation-free' meta-analysis with
proxy-{SNP}s.},
journal = {BMC bioinformatics},
volume = {13},
number = {1},
issn = {1471-2105},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2020-02979},
pages = {231},
year = {2012},
abstract = {Meta-analysis (MA) is widely used to pool genome-wide
association studies (GWASes) in order to a) increase the
power to detect strong or weak genotype effects or b) as a
result verification method. As a consequence of differing
SNP panels among genotyping chips, imputation is the method
of choice within GWAS consortia to avoid losing too many
SNPs in a MA. YAMAS (Yet Another Meta Analysis Software),
however, enables cross-GWAS conclusions prior to finished
and polished imputation runs, which eventually are
time-consuming.Here we present a fast method to avoid
forfeiting SNPs present in only a subset of studies, without
relying on imputation. This is accomplished by using
reference linkage disequilibrium data from 1,000
Genomes/HapMap projects to find proxy-SNPs together with
in-phase alleles for SNPs missing in at least one study. MA
is conducted by combining association effect estimates of a
SNP and those of its proxy-SNPs. Our algorithm is
implemented in the MA software YAMAS. Association results
from GWAS analysis applications can be used as input files
for MA, tremendously speeding up MA compared to the
conventional imputation approach. We show that our proxy
algorithm is well-powered and yields valuable ad hoc
results, possibly providing an incentive for follow-up
studies. We propose our method as a quick screening step
prior to imputation-based MA, as well as an additional main
approach for studies without available reference data
matching the ethnicities of study participants. As a proof
of principle, we analyzed six dbGaP Type II Diabetes GWAS
and found that the proxy algorithm clearly outperforms
naïve MA on the p-value level: for 17 out of 23 we observe
an improvement on the p-value level by a factor of more than
two, and a maximum improvement by a factor of 2127.YAMAS is
an efficient and fast meta-analysis program which offers
various methods, including conventional MA as well as
inserting proxy-SNPs for missing markers to avoid
unnecessary power loss. MA with YAMAS can be readily
conducted as YAMAS provides a generic parser for
heterogeneous tabulated file formats within the GWAS field
and avoids cumbersome setups. In this way, it supplements
the meta-analysis process.},
keywords = {Algorithms / Alleles / Diabetes Mellitus, Type 2: genetics
/ Genome, Human / Genome-Wide Association Study / Genotype /
HapMap Project / Humans / Linkage Disequilibrium /
Meta-Analysis as Topic / Polymorphism, Single Nucleotide /
Software},
cin = {GenomMathematik / AG Roes},
ddc = {610},
cid = {I:(DE-2719)1013007 / I:(DE-2719)1610003},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22971100},
pmc = {pmc:PMC3472171},
doi = {10.1186/1471-2105-13-231},
url = {https://pub.dzne.de/record/136657},
}