Dementias Platform UK: Bringing genetics into life.
dementia
genetic data
harmonization
imputation
polygenic risk scores
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
20 Mar 2024
20 Mar 2024
Historique:
revised:
21
12
2023
received:
06
09
2023
accepted:
29
01
2024
medline:
20
3
2024
pubmed:
20
3
2024
entrez:
20
3
2024
Statut:
aheadofprint
Résumé
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. 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. 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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : MRC
ID : MR/L023784/2
Organisme : MRC
ID : MR/T033371/1
Organisme : MRC
ID : MR/L010305/1
Organisme : MRC
ID : UKDRI-3003
Organisme : Alzheimer's disease
ID : ARUK-PG2014-2
Organisme : Brains for Dementia Research
ID : ARUK-EXT2017A-1
Informations de copyright
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Bauermeister S, Orton C, Thompson S, et al. The Dementias Platform UK (DPUK) data portal. Eur J Epidemiol. 2020;35:601-611. doi:10.1007/s10654-020-00633-4
Chen W, Hu Y, Ju D. Gene therapy for neurodegenerative disorders: advances, insights and prospects. Acta Pharm Sin B. 2020:10:1347-1359. doi:10.1016/j.apsb.2020.01.015
Escott-Price V, Shoai M, Pither R, Williams J, Hardy J. Polygenic score prediction captures nearly all common genetic risk for Alzheimer's disease. Neurobiol Aging. 2017;49:214.e7-214.e11. doi:10.1016/j.neurobiolaging.2016.07.018
Escott-Price V, Myers AJ, Huentelman M, Hardy J. Polygenic risk score analysis of pathologically confirmed Alzheimer disease. Ann Neurol. 2017;82:311-314. doi:10.1002/ana.24999
Creese B, Vassos E, Bergh S, et al. Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer's disease. Transl Psychiatry. 2019;9. doi:10.1038/S41398-019-0592-5
Bellou E, Stevenson-Hoare J, Escott-Price V. Polygenic risk and pleiotropy in neurodegenerative diseases. Neurobiol Dis. 2020;142. doi:10.1016/J.NBD.2020.104953
Sudlow C, Gallacher J, Allen N, et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12(3). doi:10.1371/journal.pmed.1001779
Caulfield M, Davies J, Dennys M, et al. National Genomic Research Library. figshare. Dataset. 2017. doi:10.6084/m9.figshare.4530893.v7
Kunkle BW, Grenier-Boley B, Sims R, et al. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet. 2019;51:44-430. doi:10.1038/s41588-019-0358-2
Nalls MA, Blauwendraat C, Vallerga CL, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019;18:1091-1102. doi:10.1016/S1474-4422(19)30320-5
Ferrari R, Hernandez DG, Nalls MA, et al. Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol. 2014;13:686-699. doi:10.1016/S1474-4422(14)70065-1
van Rheenen W, van der Spek RAA, Bakker MK, et al. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology. Nat Genet. 2021;53:1636-1648. doi:10.1038/s41588-021-00973-1
Chia R, Sabir MS, Bandres-Ciga S, et al. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nat Genet. 2021;53:294-303. doi:10.1038/s41588-021-00785-3
Chang CC, Chow CC, Tellier LCCAM, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4:7. doi:10.1186/s13742-015-0047-8
Francis PT, Costello H, Hayes GM. Brains for dementia research: evolution in a longitudinal brain donation cohort to maximize current and future value. J Alzheimer's Dis. 2018;66:1635-1644. doi:10.3233/JAD-180699
Young J, Gallagher E, Koska K, et al. Genome-wide association findings from the brains for dementia research cohort. Neurobiol Aging. 2021;107:159-167. doi:10.1016/J.NEUROBIOLAGING.2021.05.014
Smith BH, Campbell A, Linksted P, et al. Cohort profile: Generation Scotland: Scottish Family Health Study (GS:SFHS). The study, its participants and their potential for genetic research on health and illness. Int J Epidemiol. 2013;42:689-700. doi:10.1093/IJE/DYS084
Hayat SA, Luben R, Keevil VL, et al. Cohort profile: a prospective cohort study of objective physical and cognitive capability and visual health in an ageing population of men and women in Norfolk (EPIC-Norfolk 3). Int J Epidemiol. 2014;43:1063-1072. doi:10.1093/IJE/DYT086
Wadsworth M, Kuh D, Richards M, Hardy R. Cohort profile: the 1946 National Birth Cohort (MRC National Survey of Health and Development). Int J Epidemiol. 2006;35:49-54. doi:10.1093/IJE/DYI201
Elliott P, Vergnaud AC, Singh D, Neasham D, Spear J, Heard A. The Airwave Health Monitoring Study of police officers and staff in Great Britain: rationale, design and methods. Environ Res. 2014;134:280-285. doi:10.1016/J.ENVRES.2014.07.025
Anderson CA, Pettersson FH, Clarke GM, Cardon LR, Morris AP, Zondervan KT. Data quality control in genetic case-control association studies. Nat Protoc. 2010;5:1564-1573. doi:10.1038/nprot.2010.116.20105:9
Howie B, Fuchsberger C, Stephens M, Marchini J, Abecasis GR. Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet. 2012;44:955-959. doi:10.1038/ng.2354
Das S, Forer L, Schönherr S, et al. Next-generation genotype imputation service and methods. Nat Genet. 2016;48:1284-1287. doi:10.1038/ng.3656
Li Y, Willer CJ, Ding J, Scheet P, MaCH AbecasisGR. Using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol. 2010;34:816-834. doi:10.1002/gepi.20533
The Haplotype Reference Consortium. A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet. 2016;48:1279-1283. doi:10.1038/ng.3643
Das S, Forer L, Schönherr S, et al. Next-generation genotype imputation service and methods. Nat Genet. 2016;48:1284-1287. doi:10.1038/ng.3656.201648:10
Bellenguez C, Küçükali F, Jansen IE, et al. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nat Genet. 2022;54:412-436. doi:10.1038/s41588-022-01024-z
Ge T, Chen CY, Ni Y, Feng YCA, Smoller JW. Polygenic prediction via Bayesian regression and continuous shrinkage priors. Nat Commun. 2019;-1. doi:10.1038/s41467-019-09718-5
Ni G, Zeng J, Revez JA, et al. A comparison of ten polygenic score methods for psychiatric disorders applied across multiple cohorts. Biol Psychiatry. 2021;90:611-620. doi:10.1016/j.biopsych.2021.04.018
Purcell SM, Wray NR, Stone JL, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009;460:748-752. doi:10.1038/nature08185
Leonenko G, Baker E, Stevenson-Hoare J, et al. Identifying individuals with high risk of Alzheimer's disease using polygenic risk scores. Nat Commun. 2021;12. doi:10.1038/s41467-021-24082-z
Choi SW, Mak TSH, Hoggart CJ, O'reilly PF. EraSOR: a software tool to eliminate inflation caused by sample overlap in polygenic score analyses. Gigascience. 2022;12:1-11. doi:10.1093/GIGASCIENCE/GIAD043
Escott-Price V, Hardy J. Genome-wide association studies for Alzheimer's disease: bigger is not always better. Brain Commun. 2022;4:1-7. doi:10.1093/BRAINCOMMS/FCAC125
Grotzinger AD, la FuenteJde, Privé F, Nivard MG, Tucker-Drob EM. Pervasive downward bias in estimates of liability-scale heritability in genome-wide association study meta-analysis: a simple solution. Biol Psychiatry. 2023;93:29-36. doi:10.1016/J.BIOPSYCH.2022.05.029
Sun Z, Wu Y, Fetcher JM, Lu Q. Pervasive biases in proxy GWAS based on parental history of Alzheimer's disease. Alzheimer's Dement. 2023;19(Suppl.12):e080435. doi:10.1002/alz.080435