Evidence map›Paper›PMID 22971100›Full record

ArticleBMC bioinformatics2012

Quick, "imputation-free" meta-analysis with proxy-SNPs.

Christian Meesters, Markus Leber, Christine Herold, Marina Angisch, Manuel Mattheisen, Dmitriy Drichel, André Lacour, Tim Becker

Abstract readEvaluation Study
In one paragraph

Article in BMC bioinformatics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

8 authors.

Christian MeestersGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Markus Leber
Christine Herold
Marina Angisch
Manuel Mattheisen
Dmitriy Drichel
André Lacour
Tim Becker

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMeta-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.

resultsHere 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.

conclusionsYAMAS 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.

Indexed as

AlgorithmsGenome-Wide Association StudyMeta-Analysis as TopicPolymorphism, Single NucleotideAllelesDiabetes Mellitus, Type 2Genome, HumanGenotypeHapMap ProjectHumansLinkage DisequilibriumSoftware

Identifiers

PMID22971100
PMCPMC3472171

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.