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000865958 0247_ $$2doi$$a10.1038/s41380-019-0463-8
000865958 0247_ $$2pmid$$apmid:31492941
000865958 0247_ $$2ISSN$$a1359-4184
000865958 0247_ $$2ISSN$$a1476-5578
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000865958 037__ $$aFZJ-2019-05224
000865958 041__ $$aeng
000865958 082__ $$a610
000865958 1001_ $$0P:(DE-HGF)0$$aHess, Jonathan L$$b0
000865958 245__ $$aA polygenic resilience score moderates the genetic risk for schizophrenia
000865958 260__ $$aLondon$$bMacmillan$$c2021
000865958 3367_ $$2DRIVER$$aarticle
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000865958 3367_ $$2BibTeX$$aARTICLE
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000865958 3367_ $$00$$2EndNote$$aJournal Article
000865958 520__ $$aBased on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531-538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known 'polygenic resilience score' that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.
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000865958 7001_ $$00000-0002-8442-493X$$aMattheisen, Manuel$$b2
000865958 7001_ $$0P:(DE-HGF)0$$aConsortium, Schizophrenia Working Group of the Psychiatric Genomics$$b3
000865958 7001_ $$0P:(DE-HGF)0$$aResearch, Lundbeck Foundation Initiative for Integrative Psychiatric$$b4
000865958 7001_ $$00000-0001-8627-7219$$aBørglum, Anders D$$b5
000865958 7001_ $$00000-0002-2963-1928$$aAls, Thomas D$$b6
000865958 7001_ $$00000-0003-2284-5744$$aGrove, Jakob$$b7
000865958 7001_ $$0P:(DE-HGF)0$$aWerge, Thomas$$b8
000865958 7001_ $$0P:(DE-HGF)0$$aMortensen, Preben Bo$$b9
000865958 7001_ $$0P:(DE-HGF)0$$aMors, Ole$$b10
000865958 7001_ $$0P:(DE-HGF)0$$aNordentoft, Merete$$b11
000865958 7001_ $$00000-0001-5928-3517$$aHougaard, David M$$b12
000865958 7001_ $$00000-0003-1705-4008$$aByberg-Grauholm, Jonas$$b13
000865958 7001_ $$0P:(DE-HGF)0$$aBækvad-Hansen, Marie$$b14
000865958 7001_ $$00000-0002-6080-6503$$aGreenwood, Tiffany A$$b15
000865958 7001_ $$0P:(DE-HGF)0$$aTsuang, Ming T$$b16
000865958 7001_ $$00000-0002-4089-9183$$aCurtis, David$$b17
000865958 7001_ $$00000-0001-7726-5152$$aSteinberg, Stacy$$b18
000865958 7001_ $$00000-0001-9404-7982$$aSigurdsson, Engilbert$$b19
000865958 7001_ $$0P:(DE-HGF)0$$aStefánsson, Hreinn$$b20
000865958 7001_ $$0P:(DE-HGF)0$$aStefánsson, Kári$$b21
000865958 7001_ $$00000-0003-0344-9690$$aEdenberg, Howard J$$b22
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000865958 7001_ $$00000-0002-9217-3982$$aFaraone, Stephen V$$b24
000865958 7001_ $$0P:(DE-HGF)0$$aGlatt, Stephen J$$b25$$eCorresponding author
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