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"=>"André 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"=>"56000233900"}, {"first_name"=>"Philipp D.", "last_name"=>"Koellinger", "scopus_author_id"=>"57193492893"}], "year"=>2017, "source"=>"PLoS Genetics", "identifiers"=>{"isbn"=>"1111111111", "pmid"=>"28095416", "pui"=>"614304502", "issn"=>"15537404", "doi"=>"10.1371/journal.pgen.1006495", "scopus"=>"2-s2.0-85011362906", "sgr"=>"85011362906"}, "id"=>"02f16a5a-be69-3fed-87a6-a2d2e3e263e6", "abstract"=>"Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of 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'. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP) calculator (available at www.devlaming.eu) which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51-62% in the number of genome-wide significant loci and a relative loss in polygenic score R2 of 36-38%). Hence, cross-study heterogeneity contributes to the missing heritability.", "link"=>"http://www.mendeley.com/research/metagwas-accuracy-power-metagap-calculator-shows-hiding-heritability-partially-due-imperfect-genetic", "reader_count"=>34, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>5, "Researcher"=>6, "Student > Ph. D. Student"=>9, "Other"=>5, "Student > Master"=>3, "Student > Bachelor"=>1, "Professor"=>3, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>5, "Researcher"=>6, "Student > Ph. D. Student"=>9, "Other"=>5, "Student > Master"=>3, "Student > Bachelor"=>1, "Professor"=>3, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>1, "Neuroscience"=>1, "Psychology"=>2, "Social Sciences"=>3, "Computer Science"=>2, "Economics, Econometrics and Finance"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>3}, "Psychology"=>{"Psychology"=>2}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>2, "United States"=>1}, "group_count"=>3}

Scopus | Further Information

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