Document Type

Journal Article

Publication Title

BMC Genomics

Volume

23

Issue

1

PubMed ID

35619096

Publisher

Springer

School

School of Medical and Health Sciences / Centre for Precision Health

RAS ID

44432

Funders

National Health and Medical Research Council Grant GNT1161706 / Commonwealth Scientific Industrial and research Organisation (CSIRO) / Edith Cowan University / Austin Health / CogState Ltd.

Grant Number

NHMRC Number : GNT1161706

Comments

Vacher, M., Doré, V., Porter, T., Milicic, L., Villemagne, V. L., Bourgeat, P., ... & Laws, S. M. (2022). Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s disease. BMC genomics, 23(1), 1-8. https://doi.org/10.1186/s12864-022-08617-2

Abstract

Background: With a growing number of loci associated with late-onset (sporadic) Alzheimer’s disease (AD), the polygenic contribution to AD is now well established. The development of polygenic risk score approaches have shown promising results for identifying individuals at higher risk of developing AD, thereby facilitating the development of preventative and therapeutic strategies. A polygenic hazard score (PHS) has been proposed to quantify age-specific genetic risk for AD. In this study, we assessed the predictive power and transferability of this PHS in an independent cohort, to support its clinical utility. Results: Using genotype and imaging data from 780 individuals enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, we investigated associations between the PHS and several AD-related traits, including 1) cross-sectional Aβ-amyloid (Aβ) deposition, 2) longitudinal brain atrophy, 3) longitudinal cognitive decline, 4) age of onset. Except in the cognitive domain, we obtained results that were consistent with previously published findings. The PHS was associated with increased Aβ burden, faster regional brain atrophy and an earlier age of onset. Conclusion: Overall, the results support the predictive power of a PHS, however, with only marginal improvement compared to apolipoprotein E alone.

DOI

10.1186/s12864-022-08617-2

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Research Themes

Health

Priority Areas

Multidisciplinary biological approaches to personalised disease diagnosis, prognosis and management

Included in

Diseases Commons

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