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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: | Psychiatric Genomics Consortium, Schizophrenia Working Group (PGC SCZ) | Publication Date: | 2015 | Open Access: | Yes | DOI: | 10.1038/ng.3211 |
Handle Link: | https://hdl.handle.net/1959.11/22039 | Open Access Link: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495769/ |
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: | 1546-1718 1061-4036 |
Fields of Research (FoR) 2008: | 060405 Gene Expression (incl. Microarray and other genome-wide approaches) | Fields of Research (FoR) 2020: | 310505 Gene expression (incl. microarray and other genome-wide approaches) | Socio-Economic Objective (SEO) 2008: | 920110 Inherited Diseases (incl. Gene Therapy) | Socio-Economic Objective (SEO) 2020: | 200101 Diagnosis of human diseases and conditions | Peer Reviewed: | Yes | HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
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| Appears in Collections: | Journal Article |
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