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      headline:Partitioning heritability by functional annotation using genome-wide association summary statistics
      description:Hilary Finucane, Brendan Bulik-Sullivan, Benjamin Neale, Alkes Price and colleagues introduce a new method, called stratified LD score regression, for partitioning heritability by functional category using genome-wide association study summary statistics. They observe a substantial enrichment of heritability in conserved regions and illustrate how this approach can provide insights into the biological basis of disease and direction for functional follow-up. Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, including cell type–specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include a large enrichment of heritability in conserved regions across many traits, a very large immunological disease–specific enrichment of heritability in FANTOM5 enhancers and many cell type–specific enrichments, including significant enrichment of central nervous system cell types in the heritability of body mass index, age at menarche, educational attainment and smoking behavior.
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         Agriculture
         Gene Function
         Animal Genetics and Genomics
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               name:Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK
               type:PostalAddress
            type:Organization
      name:Yukinori Okada
      affiliation:
            name:Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
            address:
               name:Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
               type:PostalAddress
            type:Organization
            name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences
            address:
               name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
               type:PostalAddress
            type:Organization
      name:Soumya Raychaudhuri
      affiliation:
            name:Brigham and Women's Hospital, Harvard Medical School
            address:
               name:Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
            name:Brigham and Women's Hospital, Harvard Medical School
            address:
               name:Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
            name:Partners Center for Personalized Genetic Medicine
            address:
               name:Partners Center for Personalized Genetic Medicine, Boston, USA
               type:PostalAddress
            type:Organization
            name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
            address:
               name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
            name:Faculty of Medical and Human Sciences, University of Manchester
            address:
               name:Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
               type:PostalAddress
            type:Organization
      name:Mark J Daly
      affiliation:
            name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School
            address:
               name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
            name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
            address:
               name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
            name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
            address:
               name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Nick Patterson
      affiliation:
            name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
            address:
               name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Benjamin M Neale
      url:http://orcid.org/0000-0003-1513-6077
      affiliation:
            name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School
            address:
               name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
            name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
            address:
               name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
            name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
            address:
               name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Alkes L Price
      affiliation:
            name:Harvard T.H. Chan School of Public Health
            address:
               name:Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
               type:PostalAddress
            type:Organization
            name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
            address:
               name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Mathematics, Massachusetts Institute of Technology, Cambridge, USA
      name:Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
      name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA
      name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
      name:Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Partners Center for Personalized Genetic Medicine, Boston, USA
      name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, UK
      name:Department of Computer Science, Harvard University, Cambridge, USA
      name:Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
      name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA
      name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, USA
      name:Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, USA
      name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA
      name:Epigenomics Program, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA
      name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK
      name:Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Department of Psychiatry, Mount Sinai School of Medicine, New York, USA
      name:Department of Psychiatry, Mount Sinai School of Medicine, New York, USA
      name:Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
      name:Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK
      name:Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
      name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
      name:Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
      name:Partners Center for Personalized Genetic Medicine, Boston, USA
      name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
      name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA
      name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA
      name:Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
      name:Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
      name:Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA
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