Polygenic risk and hazard scores for Alzheimer's disease prediction

Ganna Leonenko; Rebecca Sims; Maryam Shoai; Aura Frizzati; Paola Bossù; Gianfranco Spalletta; Nick C Fox; Julie Williams; John Hardy; Valentina Escott-Price; Magda Tsolaki; David Craig; Despoina Avramidou; Antonia Germanou; Maria Koutroumani; Olymbia Gkatzima; Harald Hampel; Patrick G Kehoe; Seth Love; David C Rubinsztein; Lutz Frölich; Bernadette Mcguinness; Janet A Johnston; Peter Passmore; Dmitriy Drichel; Martin Rossor; Jonathan M Schott; Jason D Warren; Jose Bras; Rita Guerreiro; Amit Kawalia Joseph T Hughes; Yogen Patel; Michelle K Lupton; Petra Proitsi; John Powell; John S K Kauwe; Michelangelo Mancuso; Ubaldo Bonuccelli; James Uphill; Elizabeth Fisher; Carlo Masullo; Hilkka Soininen; Gina Bisceglio; Li Ma; Dennis W Dickson; Neill R Graff-Radford; Minerva M Carrasquillo; Steven G Younkin; Sandro Sorbi; Makrina Daniilidou; Angela Hodges; Daniela Galimberti; Elio Scarpini; Martin Scherer; Oliver Peters; Alfredo Ramirez; Markus Leber; Sabrina Pichler; Manuel Mayhaus; Wei Gu; Matthias Riemenschneider; Jens Wiltfang; Reinhard Heun; Heike Kölsch; Johannes Kornhuber; Isabella Heuser; Dan Rujescu; Annette M Hartmann; Ina Giegling; Michael Hüll; Simon Lovestone; Carlos Cruchaga; John Morris; Kevin Mayo; Thomas Feulner; Rebecca Sussams; Clive Holmes; David Mann; Stuart Pickering-Brown; Nigel M Hooper; Andrew Mcquillin; Gill Livingston; Nicholas J Bass; Maria Vronskaya; Taniesha Morgan; Nicola Denning; Thomas D Cushion; Lesley Jones; Rachel Marshall; Alun Meggy; Georgina Menzies; Detelina Grozeva; Michael C O'Donovan; Michael J Owen; Peter A Holmans; Francesca Salani; Giancarlo Russo; Wolfgang Maier; Frank Jessen; H-Erich Wichmann; Kevin Morgan; Alison M Goate; Bruno Vellas; Emma Vardy; Susanne Moebus; Karl-Heinz Jöckel; Martin Dichgans; Norman Klopp; James Turton; Jenny Lord; Kristelle Brown; Christopher Medway; Markus M Nöthen; Per Hoffmann; Antonio Daniele; Anthony Bayer; John Gallacher; Hendrik van Den Bussche; Carol Brayne; Steffi Riedel-Heller; John F Powell; Ammar Al-Chalabi; Christopher E Shaw; Iwona Kloszewska; Pau Pastor; Monica Diez-Fairen; Aoibhinn Lynch; Brian Lawlor; Michael Gill; Eliecer Coto; Victoria Alvarez; Andrew B Singleton; John Collinge; Simon Mead; Natalie Ryan; Benedetta Nacmias; Sara Ortega-Cubero; Eloy Rodriguez-Rodriguez; Pascual Sanchez-Juan; Jacob Shofany; Nerisa Banaj; Valentina Ciullo; Eleonora Sacchinelli; Robert Clarke; a David Smith; Donald Warden; Yoav Ben-Shlomo; Chiara Cupidi; Raffaele Giovanni Maletta; Amalia Cecilia Bruni; Maura Gallo; Denise Harold; Roberta Cecchetti; Patrizia Mecocci; Virginia Boccardi; Nick Warner; Gordon Wilcock; Panagiotis Deloukas; Rhian Gwilliam; Chris Corcoran; Joann Tschanz; Ron Munger

doi:10.1002/acn3.716

Journal Articles Annals of Clinical and Translational Neurology Year : 2019

Polygenic risk and hazard scores for Alzheimer's disease prediction

(1) , (1) , (2) , (1) , (3) , (3) , (2) , (1) , (2) , (1) , , , , , , , (4) , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

1
2
3
4

Ganna Leonenko

Function : Author
PersonId : 1348728
ORCID : 0000-0001-8025-661X

Cardiff University

Rebecca Sims

Function : Author

Cardiff University

Maryam Shoai

Function : Author

University College of London [London]

Aura Frizzati

Function : Author

Cardiff University

Paola Bossù

Function : Author

Fondazione Santa Lucia [IRCCS]

Gianfranco Spalletta

Function : Author

Fondazione Santa Lucia [IRCCS]

Nick C Fox

Function : Author

University College of London [London]

Julie Williams

Function : Author

Cardiff University

John Hardy

Function : Author

University College of London [London]

Valentina Escott-Price

Function : Author

Cardiff University

Magda Tsolaki

Function : Author

David Craig

Function : Author

Despoina Avramidou

Function : Author

Antonia Germanou

Function : Author

Maria Koutroumani

Function : Author

Olymbia Gkatzima

Function : Author

Harald Hampel

Function : Author

Institut du Cerveau = Paris Brain Institute

Patrick G Kehoe

Function : Author

Seth Love

Function : Author

David C Rubinsztein

Function : Author

Lutz Frölich

Function : Author

Bernadette Mcguinness

Function : Author

Janet A Johnston

Function : Author

Peter Passmore

Function : Author

Dmitriy Drichel

Function : Author

Martin Rossor

Function : Author

Jonathan M Schott

Function : Author

Jason D Warren

Function : Author

Jose Bras

Function : Author

Rita Guerreiro

Function : Author

Amit Kawalia Joseph T Hughes

Function : Author

Yogen Patel

Function : Author

Michelle K Lupton

Function : Author

Petra Proitsi

Function : Author

John Powell

Function : Author

John S K Kauwe

Function : Author

Michelangelo Mancuso

Function : Author

Ubaldo Bonuccelli

Function : Author

James Uphill

Function : Author

Elizabeth Fisher

Function : Author

Carlo Masullo

Function : Author

Hilkka Soininen

Function : Author

Gina Bisceglio

Function : Author

Li Ma

Function : Author

Dennis W Dickson

Function : Author

Neill R Graff-Radford

Function : Author

Minerva M Carrasquillo

Function : Author

Steven G Younkin

Function : Author

Sandro Sorbi

Function : Author

Makrina Daniilidou

Function : Author

Angela Hodges

Function : Author

Daniela Galimberti

Function : Author

Elio Scarpini

Function : Author

Martin Scherer

Function : Author

Oliver Peters

Function : Author

Alfredo Ramirez

Function : Author

Markus Leber

Function : Author

Sabrina Pichler

Function : Author

Manuel Mayhaus

Function : Author

Wei Gu

Function : Author

Matthias Riemenschneider

Function : Author

Jens Wiltfang

Function : Author

Reinhard Heun

Function : Author

Heike Kölsch

Function : Author

Johannes Kornhuber

Function : Author

Isabella Heuser

Function : Author

Dan Rujescu

Function : Author

Annette M Hartmann

Function : Author

Ina Giegling

Function : Author

Michael Hüll

Function : Author

Simon Lovestone

Function : Author

Carlos Cruchaga

Function : Author

John Morris

Function : Author

Kevin Mayo

Function : Author

Thomas Feulner

Function : Author

Rebecca Sussams

Function : Author

Clive Holmes

Function : Author

David Mann

Function : Author

Stuart Pickering-Brown

Function : Author

Nigel M Hooper

Function : Author

Andrew Mcquillin

Function : Author

Gill Livingston

Function : Author

Nicholas J Bass

Function : Author

Maria Vronskaya

Function : Author

Taniesha Morgan

Function : Author

Nicola Denning

Function : Author

Thomas D Cushion

Function : Author

Lesley Jones

Function : Author

Rachel Marshall

Function : Author

Alun Meggy

Function : Author

Georgina Menzies

Function : Author

Detelina Grozeva

Function : Author

Michael C O'Donovan

Function : Author

Michael J Owen

Function : Author

Peter A Holmans

Function : Author

Francesca Salani

Function : Author

Giancarlo Russo

Function : Author

Wolfgang Maier

Function : Author

Frank Jessen

Function : Author

H-Erich Wichmann

Function : Author

Kevin Morgan

Function : Author

Alison M Goate

Function : Author

Bruno Vellas

Function : Author
PersonId : 933362
ORCID : 0000-0002-7678-5065
IdRef : 03566729X

Emma Vardy

Function : Author

Susanne Moebus

Function : Author

Karl-Heinz Jöckel

Function : Author

Martin Dichgans

Function : Author

Norman Klopp

Function : Author

James Turton

Function : Author

Jenny Lord

Function : Author

Kristelle Brown

Function : Author

Christopher Medway

Function : Author

Markus M Nöthen

Function : Author

Per Hoffmann

Function : Author

Antonio Daniele

Function : Author

Anthony Bayer

Function : Author

John Gallacher

Function : Author

Hendrik van Den Bussche

Function : Author

Carol Brayne

Function : Author

Steffi Riedel-Heller

Function : Author

John F Powell

Function : Author

Ammar Al-Chalabi

Function : Author

Christopher E Shaw

Function : Author

Iwona Kloszewska

Function : Author

Pau Pastor

Function : Author

Monica Diez-Fairen

Function : Author

Aoibhinn Lynch

Function : Author

Brian Lawlor

Function : Author

Michael Gill

Function : Author

Eliecer Coto

Function : Author

Victoria Alvarez

Function : Author

Andrew B Singleton

Function : Author

John Collinge

Function : Author

Simon Mead

Function : Author

Natalie Ryan

Function : Author

Benedetta Nacmias

Function : Author

Sara Ortega-Cubero

Function : Author

Eloy Rodriguez-Rodriguez

Function : Author

Pascual Sanchez-Juan

Function : Author

Jacob Shofany

Function : Author

Nerisa Banaj

Function : Author

Valentina Ciullo

Function : Author

Eleonora Sacchinelli

Function : Author

Robert Clarke

Function : Author

a David Smith

Function : Author

Donald Warden

Function : Author

Yoav Ben-Shlomo

Function : Author

Chiara Cupidi

Function : Author

Raffaele Giovanni Maletta

Function : Author

Amalia Cecilia Bruni

Function : Author

Maura Gallo

Function : Author

Denise Harold

Function : Author

Roberta Cecchetti

Function : Author

Patrizia Mecocci

Function : Author

Virginia Boccardi

Function : Author

Nick Warner

Function : Author

Gordon Wilcock

Function : Author

Panagiotis Deloukas

Function : Author

Rhian Gwilliam

Function : Author

Chris Corcoran

Function : Author

Joann Tschanz

Function : Author

Ron Munger

Function : Author

Abstract

Abstract Objective Genome‐wide association studies ( GWAS ) have identified over 30 susceptibility loci associated with Alzheimer's disease ( AD ). Using AD GWAS data from the International Genomics of Alzheimer's Project ( IGAP ), Polygenic Risk Score ( PRS ) was successfully applied to predict life time risk of AD development. A recently introduced Polygenic Hazard Score ( PHS ) is able to quantify individuals with age‐specific genetic risk for AD . The aim of this study was to quantify the age‐specific genetic risk for AD with PRS and compare the results generated by PRS with those from PHS . Methods Quantification of individual differences in age‐specific genetic risk for AD identified by the PRS , was performed with Cox Regression on 9903 (2626 cases and 7277 controls) individuals from the Genetic and Environmental Risk in Alzheimer's Disease consortium ( GERAD ). Polygenic Hazard Scores were generated for the same individuals. The age‐specific genetic risk for AD identified by the PRS was compared with that generated by the PHS . This was repeated using varying SNP s P ‐value thresholds for disease association. Results Polygenic Risk Score significantly predicted the risk associated with age at AD onset when SNP s were preselected for association to AD at P ≤ 0.001. The strongest effect ( B = 0.28, SE = 0.04, P = 2.5 × 10 −12 ) was observed for PRS based upon genome‐wide significant SNP s ( P ≤ 5 × 10 −8 ). The strength of association was weaker with less stringent SNP selection thresholds. Interpretation Both PRS and PHS can be used to predict an age‐specific risk for developing AD . The PHS approach uses SNP effect sizes derived with the Cox Proportional Hazard Regression model. When SNP s were selected based upon AD GWAS case/control P ≤ 10 −3 , we found no advantage of using SNP effects sizes calculated with the Cox Proportional Hazard Regression model in our study. When SNP s are selected for association with AD risk at P > 10 −3 , the age‐specific risk prediction results are not significant for either PRS or PHS . However PHS could be more advantageous than PRS of age specific AD risk predictions when SNP s are prioritized for association with AD age at onset (i.e., powerful Cox Regression GWAS study).

Domains

Human health and pathology

Fichier principal

Ann Clin Transl Neurol - 2019 - Leonenko - Polygenic risk and hazard scores for Alzheimer s disease prediction.pdf (432.96 Ko)

Origin	Publication funded by an institution
Licence	Attribution

Gestionnaire HAL 5 Sorbonne Université : Connect in order to contact the contributor

https://hal.sorbonne-universite.fr/hal-04444983

Submitted on : Wednesday, February 7, 2024-5:26:03 PM

Last modification on : Friday, March 15, 2024-9:24:40 AM

Dates and versions

hal-04444983 , version 1 (07-02-2024)

Licence

Attribution

Identifiers

HAL Id : hal-04444983 , version 1
DOI : 10.1002/acn3.716
PUBMED : 30911569
PUBMEDCENTRAL : PMC6414493

Cite

Ganna Leonenko, Rebecca Sims, Maryam Shoai, Aura Frizzati, Paola Bossù, et al.. Polygenic risk and hazard scores for Alzheimer's disease prediction. Annals of Clinical and Translational Neurology, 2019, 6 (3), pp.456-465. ⟨10.1002/acn3.716⟩. ⟨hal-04444983⟩

Export

BibTeX XML-TEI Dublin Core DC Terms EndNote DataCite

Collections

CNRS ICM SORBONNE-UNIVERSITE SU-MEDECINE

40 View

16 Download

Polygenic risk and hazard scores for Alzheimer's disease prediction

Abstract

Domains

Dates and versions

Licence

Identifiers

Cite

Export

Collections

Altmetric

Share