Publication Date

2015

Journal Title

Nat Genet

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.

Volume Number

47

Issue Number

3

Pages

291-5

Document Type

Article

EPub Date

2015/02/03

Status

Faculty

Facility

School of Medicine

Primary Department

Psychiatry

Additional Departments

Molecular Medicine

PMID

25642630

DOI

10.1038/ng.3211


Included in

Psychiatry Commons

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