Global InformationLinkage disequilibrium score regression information
In statistical genetics, linkage disequilibrium score regression (LDSR[1] or LDSC[2]) is a technique that aims to quantify the separate contributions of polygenic effects and various confounding factors, such as population stratification, based on summary statistics from genome-wide association studies (GWASs). The approach involves using regression analysis to examine the relationship between linkage disequilibrium scores and the test statistics of the single-nucleotide polymorphisms (SNPs) from the GWAS. Here, the "linkage disequilibrium score" for a SNP "is the sum of LD r2 measured with all other SNPs".[3]
LDSC can be used to produce SNP-based heritability estimates, to partition this heritability into separate categories, and to calculate genetic correlations between separate phenotypes. Because the LDSC approach relies only on summary statistics from an entire GWAS, it can be used efficiently even with very large sample sizes.[4] In LDSC, genetic correlations are calculated based on the deviation between chi-square statistics and what would be expected assuming the null hypothesis.[1]
- ^ a b Levinson, Douglas F.; Noordsy, Douglas L.; Hardy, Kate V.; Ballon, Jacob S.; Shen, Hanyang; Duncan, Laramie E. (2018-10-17). "Genetic Correlation Profile of Schizophrenia Mirrors Epidemiological Results and Suggests Link Between Polygenic and Rare Variant (22q11.2) Cases of Schizophrenia". Schizophrenia Bulletin. 44 (6): 1350–1361. doi:10.1093/schbul/sbx174. ISSN 0586-7614. PMC 6192473. PMID 29294133.
- ^ Ni, Guiyan; Moser, Gerhard; Wray, Naomi R.; Lee, S. Hong; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T.R.; Farh, Kai-How (June 2018). "Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood". The American Journal of Human Genetics. 102 (6): 1185–1194. doi:10.1016/j.ajhg.2018.03.021. ISSN 0002-9297. PMC 5993419. PMID 29754766.
- ^ Neale, Benjamin M.; Price, Alkes L.; Daly, Mark J.; Patterson, Nick; Consortium, Schizophrenia Working Group of the Psychiatric Genomics; Yang, Jian; Ripke, Stephan; Finucane, Hilary K.; Loh, Po-Ru (March 2015). "LD Score regression distinguishes confounding from polygenicity in genome-wide association studies". Nature Genetics. 47 (3): 291–295. doi:10.1038/ng.3211. ISSN 1546-1718. PMC 4495769. PMID 25642630.
- ^ Neale, Benjamin M.; Evans, David M.; Gaunt, Tom R.; Paternoster, Lavinia; Anttila, Verneri; Bulik-Sullivan, Brendan K.; Price, Alkes L.; Finucane, Hilary K.; Warrington, Nicole M. (2017-01-15). "LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis". Bioinformatics. 33 (2): 272–279. doi:10.1093/bioinformatics/btw613. hdl:2381/38771. ISSN 1367-4803. PMC 5542030. PMID 27663502.