A polygenic resilience score moderates the genetic risk for schizophrenia

JL Hess; DS Tylee; M Mattheisen; AD Børglum; TD Als; J Grove; T Werge; PB Mortensen; O Mors; M Nordentoft; DM Hougaard; J Byberg-Grauholm; M Bækvad-Hansen; TA Greenwood; MT Tsuang; D Curtis; S Steinberg; E Sigurdsson; H Stefánsson; K Stefánsson; HJ Edenberg; P Holmans; SV Faraone; SJ Glatt; R Adolfsson; I Agartz; E Agerbo; M Albus; M Alexander; F Amin; OA Andreassen; MJ Arranz; SA Bacanu; S Bakker; G Band; I Barroso; M Begemann; C Bellenguez; RA Belliveau; S Bender; J Bene; SE Bergen; E Bevilacqua; TB Bigdeli; DW Black; H Blackburn; JM Blackwell; DHR Blackwood; E Bramon; MA Brown; R Bruggeman; NG Buccola; RL Buckner; B Bulik-Sullivan; SJ Bumpstead; JD Buxbaum; W Byerley; W Cahn; G Cai; D Campion; RM Cantor; VJ Carr; N Carrera; JP Casas; SV Catts; KD Chambert; RYL Chan; RCK Chan; EYH Chen; W Cheng; EFC Cheung; SA Chong; S Cichon; CR Cloninger; D Cohen; N Cohen; DA Collier; P Cormican; A Corvin; N Craddock; B Crespo-Facorro; JJ Crowley; MJ Daly; A Darvasi; M Davidson; KL Davis; F Degenhardt; J Del Favero; P Deloukas; D Demontis; D Dikeos; T Dinan; S Djurovic; E Domenici; P Donnelly; G Donohoe; E Drapeau; S Dronov; J Duan; F Dudbridge

Journal article

A polygenic resilience score moderates the genetic risk for schizophrenia

JL Hess, DS Tylee, M Mattheisen, AD Børglum, TD Als, J Grove, T Werge, PB Mortensen, O Mors, M Nordentoft, DM Hougaard, J Byberg-Grauholm, M Bækvad-Hansen, TA Greenwood, MT Tsuang, D Curtis, S Steinberg, E Sigurdsson, H Stefánsson, K Stefánsson Show all

Molecular Psychiatry | SPRINGERNATURE | Published : 2021

DOI: 10.1038/s41380-019-0463-8

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Abstract

Based 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..

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