Format

Send to

Choose Destination
Mol Psychiatry. 2019 Sep 6. doi: 10.1038/s41380-019-0463-8. [Epub ahead of print]

A polygenic resilience score moderates the genetic risk for schizophrenia.

Collaborators (361)

Adolfsson R, Agartz I, Agerbo E, Albus M, Alexander M, Amin F, Andreassen OA, Arranz MJ, Bacanu SA, Bakker S, Band G, Barroso I, Begemann M, Bellenguez C, Belliveau RA Jr, Bender S, Bene J, Bergen SE, Bevilacqua E, Bigdeli TB, Black DW, Blackburn H, Blackwell JM, Blackwood DHR, Bramon E, Brown MA, Bruggeman R, Buccola NG, Buckner RL, Bulik-Sullivan B, Bumpstead SJ, Buxbaum JD, Byerley W, Cahn W, Cai G, Campion D, Cantor RM, Carr VJ, Carrera N, Casas JP, Catts SV, Chambert KD, Chan RYL, Chan RCK, Chen EYH, Cheng W, Cheung EFC, Chong SA, Cichon S, Cloninger CR, Cohen D, Cohen N, Collier DA, Cormican P, Corvin A, Craddock N, Crespo-Facorro B, Crowley JJ, Daly MJ, Darvasi A, Davidson M, Davis KL, Degenhardt F, Del Favero J, Deloukas P, Demontis D, Dikeos D, Dinan T, Djurovic S, Domenici E, Donnelly P, Donohoe G, Drapeau E, Dronov S, Duan J, Dudbridge F, Duncanson A, Durmishi N, Edkins S, Ehrenreich H, Eichhammer P, Eriksson J, Escott-Price V, Esko T, Essioux L, Fanous AH, Farh KH, Farrell MS, Frank J, Franke L, Freedman R, Freeman C, Freimer NB, Friedl M, Friedman JI, Fromer M, Gejman PV, Genovese G, Georgieva L, Giannoulatou E, Giegling I, Gill M, Gillman M, Giusti-Rodríguez P, Godard S, Goldstein JI, Golimbet V, Gopal S, Gratten J, Gray E, Gurling H, Gwilliam R, de Haan L, Hall J, Hammer C, Hammond N, Hamshere ML, Hansen M, Hansen T, Haroutunian V, Hartmann AM, Hellenthal G, Henskens FA, Herms S, Hirschhorn JN, Hoffmann P, Hofman A, Hollegaard MV, Huang H, Hultman CM, Hunt SE, Ikeda M, Iwata N, Iyegbe C, Jablensky AV, Jankowski J, Jayakumar A, Joa I, Jönsson EG, Julià A, Kähler AK, Kahn RS, Kalaydjieva L, Karachanak-Yankova S, Karjalainen J, Kavanagh D, Keller MC, Kendler KS, Kennedy JL, Khrunin A, Kim Y, Kirov G, Klovins J, Knight J, Knowles JA, Konte B, Kucinskas V, Kucinskiene ZA, Kuzelova-Ptackova H, Langford C, Laurent C, Lawrie S, Lee SH, Lee P, Lee J, Legge SE, Lencz T, Lerer B, Levinson DF, Lewis CM, Li T, Li QS, Li M, Liang KY, Liddle J, Lieberman J, Limborska S, Lin K, Linszen DH, Liu J, Lönnqvist J, Loughland CM, Lubinski J, Macek M, Magnusson PKE, Maher BS, Maier W, Malhotra AK, Mallet J, Markus HS, Marsal S, Mata I, Mathew CG, Mattingsdal M, McCann OT, McCarley RW, McCarroll SA, McCarthy MI, McDonald C, McIntosh AM, McQuillin A, Meier S, Meijer CJ, Melegh B, Melle I, Mesholam-Gately RI, Metspalu A, Michie PT, Milani L, Milanova V, Mokrab Y, Moran JL, Morris DW, Mowry BJ, Müller-Myhsok B, Murphy KC, Murray RM, Myin-Germeys I, Neale BM, Nelis M, Nenadic I, Nertney DA, Nestadt G, Nicodemus KK, Nikitina-Zake L, Nisenbaum L, Nordin A, Nöthen MM, O'Callaghan E, O'Donovan MC, O'Dushlaine C, O'Neill FA, Oh SY, Olincy A, Olsen L, Ophoff RA, Van Os J, Owen MJ, Palmer CNA, Palotie A, Pantelis C, Papadimitriou GN, Papiol S, Parkhomenko E, Pato MT, Pato CN, Paunio T, Pearson R, Cairns MJ, DeLisi LE, Gershon ES, Kelly BJ, Lam M, Norgren N, Paciga SA, Tooney PA, Wu JQ, Pejovic-Milovancevic M, Perkins DO, Pers TH, Petryshen TL, Pietiläinen O, Pimm J, Pirinen M, Plomin R, Pocklington AJ, Posthuma D, Potter SC, Powell J, Price A, Pulver AE, Purcell SM, Quested D, Rasmussen HB, Rautanen A, Ravindrarajah R, Reichenberg A, Reimers MA, Richards AL, Ricketts M, Rietschel M, Riley BP, Ripke S, Roffman JL, Roussos P, Ruderfer DM, Rujescu D, Salomaa V, Sanders AR, Sawcer SJ, Schall U, Schubert CR, Schulze TG, Schwab SG, Scolnick EM, Scott RJ, Seidman LJ, Sham PC, Shi J, Sigurdsson E, Silagadze T, Silverman JM, Sim K, Sklar P, Slominsky P, Smoller JW, So HC, Söderman E, Spencer CCA, Clair DS, Stahl EA, Stogmann E, Strange A, Straub RE, Strengman E, Strohmaier J, Stroup TS, Su Z, Subramaniam M, Sullivan PF, Suvisaari J, Svrakic DM, Szatkiewicz JP, Tashakkori-Ghanbaria A, Thirumalai S, Toncheva D, Tosato S, Trembath RC, Veijola J, Visscher PM, Viswanathan AC, Vukcevic D, Waddington J, Waller M, Walsh D, Walshe M, Walters JTR, Wang Q, Wang D, Webb BT, Weinberger DR, Weisbrod M, Weiser M, Wendland JR, Weston P, Whittaker P, Widaa S, Wiersma D, Wildenauer DB, Williams S, Williams NM, Witt SH, Wolen AR, Wong EHM, Wood NW, Wormley BK, Wray NR, Xi HS, Zai CC, Zheng X, Zimprich F.

Author information

1
Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA.
2
Department of Psychiatry, Yale New Haven Hospital, New Haven, CT, USA.
3
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen, Denmark.
4
iSEQ, Center for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
5
Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark.
6
Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
7
Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
8
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
9
National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.
10
Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark.
11
Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
12
Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
13
Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
14
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
15
University College London Genetics Institute, London, UK.
16
Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, London, UK.
17
deCODE Genetics/Amgen, Reykjavik, Iceland.
18
Department of Psychiatry, National University Hospital, Reykjavik, Iceland.
19
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
20
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
21
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
22
Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
23
Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA. stephen.glatt@psychgenelab.com.
24
Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA. stephen.glatt@psychgenelab.com.
25
Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, Syracuse, NY, USA. stephen.glatt@psychgenelab.com.

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 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.

PMID:
31492941
DOI:
10.1038/s41380-019-0463-8

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center