Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s disease
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 de...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-022-08617-2 |
| _version_ | 1818213839892643840 |
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| author | Michael Vacher Vincent Doré Tenielle Porter Lidija Milicic Victor L. Villemagne Pierrick Bourgeat Sam C. Burnham Timothy Cox Colin L. Masters Christopher C. Rowe Jurgen Fripp James D. Doecke Simon M. Laws |
| author_facet | Michael Vacher Vincent Doré Tenielle Porter Lidija Milicic Victor L. Villemagne Pierrick Bourgeat Sam C. Burnham Timothy Cox Colin L. Masters Christopher C. Rowe Jurgen Fripp James D. Doecke Simon M. Laws |
| author_sort | Michael Vacher |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T06:10:40Z |
| format | Article |
| id | doaj.art-922fd30cfa5d4aa2bb78f823a53ae0a8 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-12T06:10:40Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-922fd30cfa5d4aa2bb78f823a53ae0a82022-12-22T00:35:10ZengBMCBMC Genomics1471-21642022-05-012311810.1186/s12864-022-08617-2Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s diseaseMichael Vacher0Vincent Doré1Tenielle Porter2Lidija Milicic3Victor L. Villemagne4Pierrick Bourgeat5Sam C. Burnham6Timothy Cox7Colin L. Masters8Christopher C. Rowe9Jurgen Fripp10James D. Doecke11Simon M. Laws12Australian e-Health Research Centre, CSIROAustralian e-Health Research Centre, CSIROCentre for Precision Health, Edith Cowan UniversityCentre for Precision Health, Edith Cowan UniversityCentre for Precision Health, Edith Cowan UniversityAustralian e-Health Research Centre, CSIROCentre for Precision Health, Edith Cowan UniversityAustralian e-Health Research Centre, CSIROFlorey Institute, The University of MelbourneDepartment of Molecular Imaging & Therapy and Centre for PET, Austin HealthAustralian e-Health Research Centre, CSIROCentre for Precision Health, Edith Cowan UniversityCentre for Precision Health, Edith Cowan UniversityAbstract 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.https://doi.org/10.1186/s12864-022-08617-2Alzheimer’s diseasePolygenic hazard scoreBrain atrophyAD onset |
| spellingShingle | Michael Vacher Vincent Doré Tenielle Porter Lidija Milicic Victor L. Villemagne Pierrick Bourgeat Sam C. Burnham Timothy Cox Colin L. Masters Christopher C. Rowe Jurgen Fripp James D. Doecke Simon M. Laws Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s disease BMC Genomics Alzheimer’s disease Polygenic hazard score Brain atrophy AD onset |
| title | Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s disease |
| title_full | Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s disease |
| title_fullStr | Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s disease |
| title_full_unstemmed | Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s disease |
| title_short | Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer’s disease |
| title_sort | assessment of a polygenic hazard score for the onset of pre clinical alzheimer s disease |
| topic | Alzheimer’s disease Polygenic hazard score Brain atrophy AD onset |
| url | https://doi.org/10.1186/s12864-022-08617-2 |
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