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LD score regression distinguishes confounding from polygenicity in genome-wide association studies

Journal Article


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.

Publication Date


  • 2015

Citation


  • Bulik-Sullivan, B., Loh, P. R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., . . . Haroutunian, V. (2015). LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nature Genetics, 47(3), 291-295. doi:10.1038/ng.3211

Scopus Eid


  • 2-s2.0-84923946495

Web Of Science Accession Number


Start Page


  • 291

End Page


  • 295

Volume


  • 47

Issue


  • 3

Place Of Publication


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.

Publication Date


  • 2015

Citation


  • Bulik-Sullivan, B., Loh, P. R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., . . . Haroutunian, V. (2015). LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nature Genetics, 47(3), 291-295. doi:10.1038/ng.3211

Scopus Eid


  • 2-s2.0-84923946495

Web Of Science Accession Number


Start Page


  • 291

End Page


  • 295

Volume


  • 47

Issue


  • 3

Place Of Publication