Please use this identifier to cite or link to this item: https://hdl.handle.net/1959.11/22039
Title: LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Contributor(s): Bulik-Sullivan, Brendan K (author); Loh, Po-Ru (author); Finucane, Hilary K (author); Ripke, Stephan (author); Yang, Jian (author); Patterson, Nick (author); Daly, Mark J (author); Price, Alkes L (author); Neale, Benjamin M (author); Corvin, Aiden (author); Hartmann, Annette M (author); Henskens, Frans A (author); Herms, Stefan (author); Hirschhorn, Joel N (author); Hoffmann, Per (author); Hofman, Andrea (author); Hollegaard, Mads V (author); Hougaard, David M (author); Hougaard, David M (author); Ikeda, Masashi (author); Walters, James TR (author); Joa, Inge (author); Julia, Antonio (author); Kahn, Rene S (author); Kalaydjieva, Luba (author); Karachanak -Yankova, Sena (author); Karjalainen, Juha (author); Kavanagh, David (author); Keller, Matthew C (author); Kelly, Brian J (author); Kennedy, James L (author); Farh, Kai-How (author); Khrunin, Andrey (author); Kim, Yunjung (author); Klovins, Janis (author); Knowles, James A (author); Konte, Bettina (author); Kucinskas, Vaidutis (author); Kucinskiene, Zita Ausrele (author); Kuzelova -Ptackova, Hana (author); Kahler, Anna K (author); Laurent, Claudine (author); Holmans, Peter A (author); Lee Chee Keong, Jimmy (author); Lee, Phil (author); Collier, David A (author); Huang, Hailiang (author); Pers, Tune H (author); Agartz, Ingrid (author); Agerbo, Esben (author); Albus, Margot (author); Alexander, Madeline (author); Amin, Farooq (author); Bacanu, Silviu (author); Begemann, Martin (author); Belliveau Jr, Richard A (author); Bene, Judit (author); Bergen, Sarah E (author); Bevilacqua, Elizabeth (author); Bigdeli, Tim B (author); Black, Donald W (author); Bruggeman, Richard (author); Buccola, Nancy G (author); Buckner, Randy L (author); Byerley, William (author); Cahn, Wiepke (author); Cai, Guiqing (author); Cairns, Murray J (author); Campion, Dominique (author); Cantor, Rita M (author); Carr, Vaughan J (author); Carrera, Noa (author); Catts, Stanley V (author); Chambert, Kimberly D (author); Chan, Raymond C K (author); Chen, Ronald Y L (author); Chen, Eric Y H (author); Cheng, Wei (author); Cheung, Eric F C (author); Chong, Siow Ann (author); Cloninger, C Robert (author); Cohen, David (author); Cohen, Nadine (author); Cormican, Paul (author); Craddock, Nick (author); Crespo- Facorro, Benedicto (author); Crowley, James J (author); Curtis, David (author); Davidson, Michael (author); Davis, Kenneth L (author); Degenhardt, Franziska (author); Favero, Jurgen D (author); DeLisi, Lynn E (author); Demontis, Ditte (author); Dikeos, Dimitris (author); Dinan, Timothy (author); Djurovic, Srdjan (author); Donohoe, Gary (author); Drapeau, Elodie (author); Duan, Jubao (author); Price, Alkes L (author); Dudbridge, Frank (author); Durmishi, Naser (author); Eichhammer, Peter (author); Eriksson, Johan (author); Escott-Price, Valentina (author); Essioux, Laurent (author); Fanous, Ayman H (author); Farrell, Martilias S (author); Frank, Josef (author); Franke, Lude (author); Freedman, Robert (author); Freimer, Nelson B (author); Friedl, Marion (author); Friedman, Joseph I (author); Fromer, Menachem (author); Genovese, Giulio (author); Georgieva, Lyudmila (author); Gershon, Elliot S (author); Giegling, Ina (author); Giusti -Rodriguez, Paola (author); Lee, Sang Hong  (author); Godard, Stephanie (author); Goldstein, Jacqueline I (author); Golimbet, Vera (author); Gopal, Srihari (author); Gratten, Jacob (author); Haan, Lieuwe de (author); Hammer, Christian (author); Hamshere, Marian L (author); Hansen, Thomas (author); Haroutunian, Vahram (author)
Corporate Author: Schizophrenia Working Group of the Psychiatric Genomics Consortium
Publication Date: 2015
Open Access: Yes
DOI: 10.1038/ng.3211Open Access Link
Handle Link: https://hdl.handle.net/1959.11/22039
Open Access Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495769/Open Access Link
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 Type: Journal Article
Source of Publication: Nature Genetics, 47(3), p. 291-295
Publisher: Nature Publishing Group
Place of Publication: United States of America
ISSN: 1061-4036
1546-1718
Field of Research (FOR): 060405 Gene Expression (incl. Microarray and other genome-wide approaches)
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
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