Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia

R. Restuadi; F.C. Garton; B. Benyamin; T. Lin; K.L. Williams; A. Vinkhuyzen; W. van Rheenen; Z. Zhu; N.G. Laing; K.A. Mather; P.S. Sachdev; S.T. Ngo; F.J. Steyn; L. Wallace; A.K. Henders; P.M. Visscher; M. Needham; S. Mathers; G. Nicholson; D.B. Rowe; R.D. Henderson; P.A. McCombe; R. Pamphlett; I.P. Blair; N.R. Wray; A.F. McRae

doi:10.1038/s41431-021-00885-y

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Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia

Journal article

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Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia

R. Restuadi, F.C. Garton, B. Benyamin, T. Lin, K.L. Williams, A. Vinkhuyzen, W. van Rheenen, Z. Zhu, N.G. Laing, K.A. Mather, …

European Journal of Human Genetics

2021

DOI: https://doi.org/10.1038/s41431-021-00885-y

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Abstract

Amyotrophic Lateral Sclerosis (ALS) is recognised to be a complex neurodegenerative disease involving both genetic and non-genetic risk factors. The underlying causes and risk factors for the majority of cases remain unknown; however, ever-larger genetic data studies and methodologies promise an enhanced understanding. Recent analyses using published summary statistics from the largest ALS genome-wide association study (GWAS) (20,806 ALS cases and 59,804 healthy controls) identified that schizophrenia (SCZ), cognitive performance (CP) and educational attainment (EA) related traits were genetically correlated with ALS. To provide additional evidence for these correlations, we built single and multi-trait genetic predictors using GWAS summary statistics for ALS and these traits, (SCZ, CP, EA) in an independent Australian cohort (846 ALS cases and 665 healthy controls). We compared methods for generating the risk predictors and found that the combination of traits improved the prediction (Nagelkerke-R2) of the case–control logistic regression. The combination of ALS, SCZ, CP, and EA, using the SBayesR predictor method gave the highest prediction (Nagelkerke-R2) of 0.027 (P value = 4.6 × 10−8), with the odds-ratio for estimated disease risk between the highest and lowest deciles of individuals being 3.15 (95% CI 1.96–5.05). These results support the genetic correlation between ALS, SCZ, CP and EA providing a better understanding of the complexity of ALS.

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Title: Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia
Authors/Creators: R. Restuadi (Author/Creator) - The University of Queensland
F.C. Garton (Author/Creator) - The University of Queensland
B. Benyamin (Author/Creator) - University of South Australia
T. Lin (Author/Creator) - The University of Queensland
K.L. Williams (Author/Creator) - Macquarie University
A. Vinkhuyzen (Author/Creator)
W. van Rheenen (Author/Creator) - University Medical Center Utrecht
Z. Zhu (Author/Creator) - The University of Queensland
N.G. Laing (Author/Creator) - The University of Western Australia
K.A. Mather (Author/Creator) - UNSW Sydney
P.S. Sachdev (Author/Creator) - Prince of Wales Hospital
S.T. Ngo (Author/Creator) - The University of Queensland
F.J. Steyn (Author/Creator) - The University of Queensland
L. Wallace (Author/Creator) - The University of Queensland
A.K. Henders (Author/Creator) - The University of Queensland
P.M. Visscher (Author/Creator) - The University of Queensland
M. Needham (Author/Creator) - Fiona Stanley Hospital
S. Mathers (Author/Creator) - Calvary Health Care Bethlehem
G. Nicholson (Author/Creator) - Concord Repatriation General Hospital
D.B. Rowe (Author/Creator) - Macquarie University
R.D. Henderson (Author/Creator) - Royal Brisbane and Women's Hospital
P.A. McCombe (Author/Creator) - Royal Brisbane and Women's Hospital
R. Pamphlett (Author/Creator) - The University of Sydney
I.P. Blair (Author/Creator) - Macquarie University
N.R. Wray (Author/Creator) - The University of Queensland
A.F. McRae (Author/Creator) - The University of Queensland
Publication Details: European Journal of Human Genetics
Publisher: Nature Publishing Group
Identifiers: 991005542238407891
Copyright: © 2021 Springer Nature Limited
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.765 ALS Mechanisms
Web Of Science research areas: Biochemistry & Molecular Biology; Genetics & Heredity
ESI research areas: Molecular Biology & Genetics