DOI . ORG {
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Title[redir]:
Partitioning heritability by functional annotation using genome-wide association summary statistics | Nature Genetics
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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pubmed, article, google, scholar, cas, nature, central, genet, data, nat, consortium, genetic, association, human, genomewide, usa, massachusetts, analysis, medical, heritability, variants, institute, genetics, access, content, raychaudhuri, cambridge, harvard, functional, finucane, buliksullivan, trynka, loci, school, supplementary, source, information, soumya, genome, complex, cell, traits, disease, wellcome, trust, authors, fig, cookies, gosia, benjamin,
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permissions reprints nature portfolio privacy policy psychiatric research body mass index schizophrenia working group advertising bipolar disorder identifies social media research genome-wide association studies cell type–specific enrichments large-scale association analysis cell-type-specific variants genome-wide association study origin-specific allelic associations leverages genome-wide information genome-wide approach accounting psychiatric genomics consortium dana-farber cancer institute multi-ancestry genetic study recently-acquired regulatory functions statistical fine-mapping studies gwas summary statistics roadmap epigenomics consortium springerlink instant access permissions nature 489 nature 518 nature 511 nature 478 nature 507 nature 467 nature 514 nature 466 nature 506 nature 491 nature 446 nature gene-level tests complex trait loci human cell types bayesian inference analyses brendan bulik-sullivan reprogen consortium epigenetic fine mapping improving fine-mapping privacy including significant enrichment rare variant association
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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 typeâspecific 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 diseaseâspecific enrichment of heritability in FANTOM5 enhancers and many cell typeâspecific 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.
datePublished:2015-09-28T00:00:00Z
dateModified:2015-09-28T00:00:00Z
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Functional genomics
Genome-wide association studies
Biomedicine
general
Human Genetics
Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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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 typeâspecific 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 diseaseâspecific enrichment of heritability in FANTOM5 enhancers and many cell typeâspecific 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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Functional genomics
Genome-wide association studies
Biomedicine
general
Human Genetics
Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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