Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

Qian Zhang; Julia Sidorenko; Baptiste Couvy-Duchesne; Riccardo E Marioni; Margaret J Wright; Alison M Goate; Edoardo Marcora; Kuan-Lin Huang; Tenielle Porter; Simon M Laws; Colin L Masters; Ashley I Bush; Christopher Fowler; David Darby; Kelly Pertile; Carolina Restrepo; Blaine Roberts; Jo Robertson; Rebecca Rumble; Tim Ryan; Steven Collins; Christine Thai; Brett Trounson; Kate Lennon; Qiao-Xin Li; Fernanda Yevenes Ugarte; Irene Volitakis; Michael Vovos; Rob Williams; Jenalle Baker; Alyce Russell; Madeline Peretti; Lidija Milicic; Lucy Lim; Mark Rodrigues; Kevin Taddei; Tania Taddei; Eugene Hone; Florence Lim; Shane Fernandez; Stephanie Rainey-Smith; Steve Pedrini; Ralph Martins; James Doecke; Pierrick Bourgeat; Jurgen Fripp; Simon Gibson; Hugo Leroux; David Hanson; Vincent Dore; Ping Zhang; Samantha Burnham; Christopher C Rowe; Victor L Villemagne; Paul Yates; Sveltana Bozin Pejoska; Gareth Jones; David Ames; Elizabeth Cyarto; Nicola Lautenschlager; Kevin Barnham; Lesley Cheng; Andy Hill; Neil Killeen; Paul Maruff; Brendan Silbert; Belinda Brown; Harmid Sohrabi; Greg Savage; Michael Vacher; Perminder S Sachdev; Karen A Mather; Nicola J Armstrong; Anbupalam Thalamuthu; Henry Brodaty; Loic Yengo; Jian Yang; Naomi R Wray; Allan F Mcrae; Peter M Visscher

doi:10.1038/s41467-020-18534-1

Journal Articles Nature Communications Year : 2020

Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

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Qian Zhang

Function : Author

The University of Queensland

Julia Sidorenko

Function : Author
PersonId : 1367554
ORCID : 0000-0003-1494-6772

The University of Queensland

Baptiste Couvy-Duchesne

Function : Author
PersonId : 739328
IdHAL : baptiste-couvy-duchesne
ORCID : 0000-0002-0719-9302

Institut du Cerveau = Paris Brain Institute

The University of Queensland

Riccardo E Marioni

Function : Author

Margaret J Wright

Function : Author
PersonId : 1188332
ORCID : 0000-0001-7133-4970

Alison M Goate

Function : Author
PersonId : 761457
ORCID : 0000-0002-0576-2472
IdRef : 186309759

Edoardo Marcora

Function : Author
PersonId : 1367555
ORCID : 0000-0002-3829-4927

Kuan-Lin Huang

Function : Author
PersonId : 1367556
ORCID : 0000-0002-5537-5817

Tenielle Porter

Function : Author

Simon M Laws

Function : Author
PersonId : 1305603
ORCID : 0000-0002-4355-7082

Colin L Masters

Function : Author

Ashley I Bush

Function : Author

Christopher Fowler

Function : Author

David Darby

Function : Author

Kelly Pertile

Function : Author

Carolina Restrepo

Function : Author

Blaine Roberts

Function : Author

Jo Robertson

Function : Author

Rebecca Rumble

Function : Author

Tim Ryan

Function : Author

Steven Collins

Function : Author

Christine Thai

Function : Author

Brett Trounson

Function : Author

Kate Lennon

Function : Author

Qiao-Xin Li

Function : Author

Fernanda Yevenes Ugarte

Function : Author

Irene Volitakis

Function : Author

Michael Vovos

Function : Author

Rob Williams

Function : Author

Jenalle Baker

Function : Author

Alyce Russell

Function : Author

Madeline Peretti

Function : Author

Lidija Milicic

Function : Author

Lucy Lim

Function : Author

Mark Rodrigues

Function : Author

Kevin Taddei

Function : Author

Tania Taddei

Function : Author

Eugene Hone

Function : Author

Florence Lim

Function : Author

Shane Fernandez

Function : Author

Stephanie Rainey-Smith

Function : Author

Steve Pedrini

Function : Author

Ralph Martins

Function : Author

James Doecke

Function : Author

Pierrick Bourgeat

Function : Author

Jurgen Fripp

Function : Author

Simon Gibson

Function : Author

Hugo Leroux

Function : Author

David Hanson

Function : Author

Vincent Dore

Function : Author

Ping Zhang

Function : Author

Samantha Burnham

Function : Author

Christopher C Rowe

Function : Author

Victor L Villemagne

Function : Author

Paul Yates

Function : Author

Sveltana Bozin Pejoska

Function : Author

Gareth Jones

Function : Author

David Ames

Function : Author

Elizabeth Cyarto

Function : Author

Nicola Lautenschlager

Function : Author

Kevin Barnham

Function : Author

Lesley Cheng

Function : Author

Andy Hill

Function : Author

Neil Killeen

Function : Author

Paul Maruff

Function : Author

Brendan Silbert

Function : Author

Belinda Brown

Function : Author

Harmid Sohrabi

Function : Author

Greg Savage

Function : Author

Michael Vacher

Function : Author

Perminder S Sachdev

Function : Author
PersonId : 778032
ORCID : 0000-0002-9595-3220
IdRef : 076727041

Karen A Mather

Function : Author

Nicola J Armstrong

Function : Author

Anbupalam Thalamuthu

Function : Author

Henry Brodaty

Function : Author
PersonId : 1305601
ORCID : 0000-0001-9487-6617

Loic Yengo

Function : Author

The University of Queensland

Jian Yang

Function : Author
PersonId : 1215658
ORCID : 0000-0003-2001-2474

The University of Queensland

Naomi R Wray

Function : Author
PersonId : 1215628
ORCID : 0000-0001-7421-3357

The University of Queensland

Allan F Mcrae

Function : Author

The University of Queensland

Peter M Visscher

Function : Author
PersonId : 1060516

The University of Queensland

Abstract

Abstract Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P -threshold ( P optimal ) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.

Domains

Human health and pathology

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s41467-020-18534-1.pdf (1.7 Mo)

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Gestionnaire HAL 2 Sorbonne Université : Connect in order to contact the contributor

https://hal.sorbonne-universite.fr/hal-04520268

Submitted on : Monday, March 25, 2024-3:45:54 PM

Last modification on : Wednesday, September 18, 2024-1:20:37 PM

Long-term archiving on : Wednesday, June 26, 2024-7:17:04 PM

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hal-04520268 , version 1 (25-03-2024)

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HAL Id : hal-04520268 , version 1
DOI : 10.1038/s41467-020-18534-1
PUBMED : 32968074
PUBMEDCENTRAL : PMC7511365

Cite

Qian Zhang, Julia Sidorenko, Baptiste Couvy-Duchesne, Riccardo E Marioni, Margaret J Wright, et al.. Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture. Nature Communications, 2020, 11 (1), pp.4799. ⟨10.1038/s41467-020-18534-1⟩. ⟨hal-04520268⟩

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Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

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