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. 2024 May;20(5):3281-3289.
doi: 10.1002/alz.13782. Epub 2024 Mar 20.

Dementias Platform UK: Bringing genetics into life

Ganna Leonenko  1 , Sarah Bauermeister  2 , Dipanwita Ghanti  2 , Joshua Stevenson-Hoare  3 , Emily Simmonds  1 , Keeley Brookes  4 , Kevin Morgan  5 , Nishi Chaturvedi  6 , Paul Elliott  7   8 , Alan Thomas  9 , Nicholas Wareham  10 , John Gallacher  2 , Valentina Escott-Price  1   3
Affiliations

Dementias Platform UK: Bringing genetics into life

Ganna Leonenko et al. Alzheimers Dement. 2024 May.

Abstract

Introduction: The Dementias Platform UK (DPUK) Data Portal is a data repository bringing together a wide range of cohorts. Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and an overlapping genetic component that is poorly understood. The DPUK collection of independent cohorts can facilitate research in neurodegeneration by combining their genetic and phenotypic data.

Methods: For genetic data processing, pipelines were generated to perform quality control analysis, genetic imputation, and polygenic risk score (PRS) derivation with six genome-wide association studies of neurodegenerative diseases. Pipelines were applied to five cohorts.

Discussion: The data processing pipelines, research-ready imputed genetic data, and PRS scores are now available on the DPUK platform and can be accessed upon request though the DPUK application process. Harmonizing genome-wide data for multiple datasets increases scientific opportunity and allows the wider research community to access and process data at scale and pace.

Keywords: dementia; genetic data; harmonization; imputation; polygenic risk scores.

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Conflict of interest statement

All authors have declared no conflicts of interest. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Flowchart of DPUK application process. DPUK, Dementias Platform UK; VDI, virtual desktop interface.
FIGURE 2
FIGURE 2
Workflow of the imputation protocol for genotyped data. HWE, Hardy–Weinberg equilibrium; MAF, minor allele frequency; SNP, single nucleotide polymorphism.
FIGURE 3
FIGURE 3
Workflow of the PRS generation protocol. APOE, apolipoprotein E; BDR, Brains for Dementia Research cohort; NSHD‐MRC Medical Research Council National Survey of Health and Development cohort; PCA, principal component analysis; PC, principal components; PRS‐CS, polygenic risk score approach calculated with 1000 Genomes reference panel.
FIGURE 4
FIGURE 4
Matrix of Pearson's correlation of PRS‐CS scores that have been calculated with six GWAS summary statistics: AD, ADRD, FTD, PD, ALS, LBD, with and without I region (AD, ADRD) in the combined cohort. APOE, apolipoprotein E; AD—clinical Alzheimer's disease GWAS; AD_no_APOE, Alzheimer's disease GWAS without APOE region; ADRD—Alzheimer's disease clinical/proxy GWAS and related dementias; ADRD_no_APOE—Alzheimer's disease clinical/proxy GWAS without APOE region; ALS, amyotrophic lateral sclerosis GWAS; FTD, frontotemporal dementia GWAS; GWAS, genome‐wide association study; LBD, Lewy body dementia; PD, Parkinson's disease GWAS.
FIGURE 5
FIGURE 5
Standardized PRS distributions calculated with AD (left) and ADRD (right) summary statistics on combined dataset split by cohort (BDR, EN, GS, NSHD, AW1, AW2, 1000G). 1000G, 1000 Genomes European population cohort; AD, Alzheimer's disease; ADRD, Alzheimer's disease and related dementias; AW, Airwave Health Monitoring Study BDR, Brains for Dementia Research; EN, Epic Norfolk; GS, Generation Scotland; NSHD, Medical Research Council National Survey of Health and Development.
See this image and copyright information in PMC

References

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