000136657 001__ 136657 000136657 005__ 20240424120353.0 000136657 0247_ $$2ISSN$$a1471-2105 000136657 0247_ $$2doi$$a10.1186/1471-2105-13-231 000136657 0247_ $$2pmid$$apmid:22971100 000136657 0247_ $$2pmc$$apmc:PMC3472171 000136657 037__ $$aDZNE-2020-02979 000136657 041__ $$aEnglish 000136657 082__ $$a610 000136657 1001_ $$0P:(DE-2719)2658768$$aMeesters, Christian$$b0$$eFirst author 000136657 245__ $$aQuick, 'imputation-free' meta-analysis with proxy-SNPs. 000136657 260__ $$aHeidelberg$$bSpringer$$c2012 000136657 264_1 $$2Crossref$$3print$$bSpringer Science and Business Media LLC$$c2012-01-01 000136657 3367_ $$2DRIVER$$aarticle 000136657 3367_ $$2DataCite$$aOutput Types/Journal article 000136657 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1713882797_10932 000136657 3367_ $$2BibTeX$$aARTICLE 000136657 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000136657 3367_ $$00$$2EndNote$$aJournal Article 000136657 520__ $$aMeta-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. 000136657 536__ $$0G:(DE-HGF)POF3-345$$a345 - Population Studies and Genetics (POF3-345)$$cPOF3-345$$fPOF III$$x0 000136657 588__ $$aDataset connected to CrossRef, PubMed, 000136657 650_2 $$2MeSH$$aAlgorithms 000136657 650_2 $$2MeSH$$aAlleles 000136657 650_2 $$2MeSH$$aDiabetes Mellitus, Type 2: genetics 000136657 650_2 $$2MeSH$$aGenome, Human 000136657 650_2 $$2MeSH$$aGenome-Wide Association Study 000136657 650_2 $$2MeSH$$aGenotype 000136657 650_2 $$2MeSH$$aHapMap Project 000136657 650_2 $$2MeSH$$aHumans 000136657 650_2 $$2MeSH$$aLinkage Disequilibrium 000136657 650_2 $$2MeSH$$aMeta-Analysis as Topic 000136657 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide 000136657 650_2 $$2MeSH$$aSoftware 000136657 7001_ $$0P:(DE-HGF)0$$aLeber, Markus$$b1 000136657 7001_ $$0P:(DE-2719)2802016$$aHerold, Christine$$b2 000136657 7001_ $$0P:(DE-HGF)0$$aAngisch, Marina$$b3 000136657 7001_ $$0P:(DE-HGF)0$$aMattheisen, Manuel$$b4 000136657 7001_ 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