@article{8348092564934278ae06ad4d9bbc6440,
title = "LD score regression distinguishes confounding from polygenicity in genome-wide association studies",
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.",
author = "{Schizophrenia Working Group of the Psychiatric Genomics Consortium} and Brendan Bulik-Sullivan and Loh, {Po Ru} and Finucane, {Hilary K.} and Stephan Ripke and Jian Yang and Nick Patterson and Daly, {Mark J.} and Price, {Alkes L.} and Neale, {Benjamin M.} and Aiden Corvin and Walters, {James T.R.} and Farh, {Kai How} and Holmans, {Peter A.} and Phil Lee and Collier, {David A.} and Hailiang Huang and Pers, {Tune H.} and Ingrid Agartz and Esben Agerbo and Margot Albus and Madeline Alexander and Farooq Amin and Bacanu, {Silviu A.} and Martin Begemann and Belliveau, {Richard A.} and Judit Bene and Bergen, {Sarah E.} and Elizabeth Bevilacqua and Bigdeli, {Tim B.} and Black, {Donald W.} and Richard Bruggeman and Buccola, {Nancy G.} and Buckner, {Randy L.} and William Byerley and Wiepke Cahn and Guiqing Cai and Cairns, {Murray J.} and Dominique Campion and Cantor, {Rita M.} and Carr, {Vaughan J.} and Noa Carrera and Catts, {Stanley V.} and Chambert, {Kimberly D.} and Chan, {Raymond C.K.} and Chen, {Ronald Y.L.} and Chen, {Eric Y.H.} and Wei Cheng and Cheung, {Eric F.C.} and Masashi Ikeda and Nakao Iwata",
note = "Funding Information: We would like to thank P. Sullivan for helpful discussion. This work was supported by US National Institutes of Health grants F32 HG007805 (P.R.L.), R01 HG006399 (A.L.P.), R03 CA173785 (H.K.F.) and R01 MH094421 (PGC) and by the Fannie and John Hertz Foundation (H.K.F.). Data on coronary artery disease and myocardial infarction were contributed by CARDIoGRAMplusC4D investigators and were downloaded from Psychiatric Genomics Consortium.",
year = "2015",
month = feb,
day = "25",
doi = "10.1038/ng.3211",
language = "English",
volume = "47",
pages = "291--295",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "3",
}