Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies
Publication Date
January 17, 2017
Authors
Ronald De Vlaming, Aysu Okbay, Cornelius A. Rietveld, Magnus Johannesson, et al
Volume
13
Issue
1
Pages
e1006495
DOI
http://doi.org/10.1371/journal.pgen.1006495
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1006495
Scopus
85011362906
Mendeley
http://www.mendeley.com/research/metagwas-accuracy-power-metagap-calculator-shows-hiding-heritability-partially-due-imperfect-genetic
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Mendeley | Further Information

{"title"=>"Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies", "type"=>"journal", "authors"=>[{"first_name"=>"Ronald", "last_name"=>"de Vlaming", "scopus_author_id"=>"56780240000"}, {"first_name"=>"Aysu", "last_name"=>"Okbay", "scopus_author_id"=>"55673500700"}, {"first_name"=>"Cornelius A.", "last_name"=>"Rietveld", "scopus_author_id"=>"57192656961"}, {"first_name"=>"Magnus", "last_name"=>"Johannesson", "scopus_author_id"=>"7103162936"}, {"first_name"=>"Patrik K E", "last_name"=>"Magnusson", "scopus_author_id"=>"24756281600"}, {"first_name"=>"Andr?? G.", "last_name"=>"Uitterlinden", "scopus_author_id"=>"35231615000"}, {"first_name"=>"Frank J A", "last_name"=>"van Rooij", "scopus_author_id"=>"6506323793"}, {"first_name"=>"Albert", "last_name"=>"Hofman", "scopus_author_id"=>"36048731400"}, {"first_name"=>"Patrick J F", "last_name"=>"Groenen", "scopus_author_id"=>"26643173600"}, {"first_name"=>"A. Roy", "last_name"=>"Thurik", "scopus_author_id"=>"6602152740"}, {"first_name"=>"Philipp D.", "last_name"=>"Koellinger", "scopus_author_id"=>"57193492893"}], "year"=>2017, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"614304502", "issn"=>"15537404", "scopus"=>"2-s2.0-85011362906", "doi"=>"10.1371/journal.pgen.1006495", "isbn"=>"1111111111", "sgr"=>"85011362906"}, "id"=>"02f16a5a-be69-3fed-87a6-a2d2e3e263e6", "abstract"=>"Large-scale GWAS results are typically obtained by meta-analyzing GWAS results from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of individual genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called 'missing' heritability. However, a theoretical multi-study framework, relating statistical power and predictive accuracy to cross-study heterogeneity, is not available. We address this gap by developing an online Meta-GWAS Accuracy and Power calculator that accounts for the cross-study genetic correlation. This calculator enables to explore to what extent an imperfect cross-study genetic correlation (i.e., less than one) contributes to the missing heritability. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy inferred by this calculator are accurate. We use the calculator to assess recent GWAS efforts and show that the effect of cross-study genetic correlation on statistical power and predictive accuracy is substantial. Hence, cross-study genetic correlation explains a considerable part of the missing heritability. Therefore, a priori calculations of statistical power and predictive accuracy, accounting for heterogeneity in genetic effects across studies, are an important tool for adequately inferring whether an intended meta-analysis of GWAS results is likely to yield meaningful outcomes.", "link"=>"http://www.mendeley.com/research/metagwas-accuracy-power-metagap-calculator-shows-hiding-heritability-partially-due-imperfect-genetic", "reader_count"=>19, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>1, "Social Sciences"=>2, "Computer Science"=>2, "Economics, Econometrics and Finance"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Social Sciences"=>{"Social Sciences"=>2}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>1}

Scopus | Further Information

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