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

2015

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

Journal Article

en

Publication

Nature Publishing Group

United States of America

10.1038/ng.3211

une:22229

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.

link

Nature Genetics, 47(3), p. 291-295

1546-1718

1061-4036

291

295