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

Author(s)
Bulik-Sullivan, Brendan K
Loh, Po-Ru
Finucane, Hilary K
Ripke, Stephan
Yang, Jian
Patterson, Nick
Daly, Mark J
Price, Alkes L
Neale, Benjamin M
Corvin, Aiden
Hartmann, Annette M
Henskens, Frans A
Herms, Stefan
Hirschhorn, Joel N
Hoffmann, Per
Hofman, Andrea
Hollegaard, Mads V
Hougaard, David M
Hougaard, David M
Ikeda, Masashi
Walters, James TR
Joa, Inge
Julia, Antonio
Kahn, Rene S
Kalaydjieva, Luba
Karachanak -Yankova, Sena
Karjalainen, Juha
Kavanagh, David
Keller, Matthew C
Kelly, Brian J
Kennedy, James L
Farh, Kai-How
Khrunin, Andrey
Kim, Yunjung
Klovins, Janis
Knowles, James A
Konte, Bettina
Kucinskas, Vaidutis
Kucinskiene, Zita Ausrele
Kuzelova -Ptackova, Hana
Kahler, Anna K
Laurent, Claudine
Holmans, Peter A
Lee Chee Keong, Jimmy
Lee, Phil
Collier, David A
Huang, Hailiang
Pers, Tune H
Agartz, Ingrid
Agerbo, Esben
Albus, Margot
Alexander, Madeline
Amin, Farooq
Bacanu, Silviu
Begemann, Martin
Belliveau Jr, Richard A
Bene, Judit
Bergen, Sarah E
Bevilacqua, Elizabeth
Bigdeli, Tim B
Black, Donald W
Bruggeman, Richard
Buccola, Nancy G
Buckner, Randy L
Byerley, William
Cahn, Wiepke
Cai, Guiqing
Cairns, Murray J
Campion, Dominique
Cantor, Rita M
Carr, Vaughan J
Carrera, Noa
Catts, Stanley V
Chambert, Kimberly D
Chan, Raymond C K
Chen, Ronald Y L
Chen, Eric Y H
Cheng, Wei
Cheung, Eric F C
Chong, Siow Ann
Cloninger, C Robert
Cohen, David
Cohen, Nadine
Cormican, Paul
Craddock, Nick
Crespo- Facorro, Benedicto
Crowley, James J
Curtis, David
Davidson, Michael
Davis, Kenneth L
Degenhardt, Franziska
Favero, Jurgen D
DeLisi, Lynn E
Demontis, Ditte
Dikeos, Dimitris
Dinan, Timothy
Djurovic, Srdjan
Donohoe, Gary
Drapeau, Elodie
Duan, Jubao
Price, Alkes L
Dudbridge, Frank
Durmishi, Naser
Eichhammer, Peter
Eriksson, Johan
Escott-Price, Valentina
Essioux, Laurent
Fanous, Ayman H
Farrell, Martilias S
Frank, Josef
Franke, Lude
Freedman, Robert
Freimer, Nelson B
Friedl, Marion
Friedman, Joseph I
Fromer, Menachem
Genovese, Giulio
Georgieva, Lyudmila
Gershon, Elliot S
Giegling, Ina
Giusti -Rodriguez, Paola
Lee, Sang Hong
Godard, Stephanie
Goldstein, Jacqueline I
Golimbet, Vera
Gopal, Srihari
Gratten, Jacob
Haan, Lieuwe de
Hammer, Christian
Hamshere, Marian L
Hansen, Thomas
Haroutunian, Vahram
Publication Date
2015
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.
Citation
Nature Genetics, 47(3), p. 291-295
ISSN
1546-1718
1061-4036
Link
Publisher
Nature Publishing Group
Title
LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Type of document
Journal Article
Entity Type
Publication

Files:

NameSizeformatDescriptionLink