Title: LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
year: 2015
Journal: Nature genetics
Volume: 47
Issue: 3
Pages: 291-295
ISSN: 1061-4036
DOI: 10.1038/ng.3211
Abstract:   Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size.;Both polygenicity ( i.e., many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of test statistic inflation in many GWAS of large sample size.;Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of the inflation in test statistics in many GWAS of large sample size.;
Notes: http://www.syndetics.com/index.aspx?isbn=/sc.gif&issn=1061-4036&client=nusing
http://www.syndetics.com/index.aspx?isbn=/mc.gif&issn=1061-4036&client=nusing
http://www.syndetics.com/index.aspx?isbn=/lc.gif&issn=1061-4036&client=nusing
U6 - ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info:sid/summon.serialssolutions.com&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=LD+Score+Regression+Distinguishes+Confounding+from+Polygenicity+in+Genome-Wide+Association+Studies&rft.jtitle=Nature+genetics&rft.au=Bulik-Sullivan%2C+Brendan+K&rft.au=Loh%2C+Po-Ru&rft.au=Finucane%2C+Hilary&rft.au=Ripke%2C+Stephan&rft.date=2015-03-01&rft.issn=1061-4036&rft.eissn=1546-1718&rft.volume=47&rft.issue=3&rft.spage=291&rft.epage=295&rft_id=info:doi/10.1038%2Fng.3211&rft_id=info:pmid/25642630&rft.externalDBID=5PM&paramdict=en-US U7 - Journal Article
URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495769/pdf/nihms683841.pdf
URI: https://open-access.imh.com.sg/handle/123456789/4812
Appears in Collections:2015




Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.