eprintid: 10161825
rev_number: 6
eprint_status: archive
userid: 699
dir: disk0/10/16/18/25
datestamp: 2022-12-15 09:18:55
lastmod: 2022-12-15 09:18:55
status_changed: 2022-12-15 09:18:55
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Mukadam, Naaheed
creators_name: Giannakopoulou, Olga
creators_name: Bass, Nick
creators_name: Kuchenbaecker, Karoline
creators_name: McQuillin, Andrew
title: Genetic risk scores and dementia risk across different ethnic groups in UK Biobank
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D79
divisions: FH4
divisions: FH5
keywords: Humans, Biological Specimen Banks, Social Group, Risk Factors, Dementia, United Kingdom
note: © 2022 Mukadam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
abstract: BACKGROUND: Genetic Risk Scores (GRS) for predicting dementia risk have mostly been used in people of European ancestry with limited testing in other ancestry groups. METHODS: We conducted a logistic regression with all-cause dementia as the outcome and z-standardised GRS as the exposure across diverse ethnic groups. FINDINGS: There was variation in frequency of APOE alleles across ethnic groups. Per standard deviation (SD) increase in z-GRS including APOE, the odds ratio (OR) for dementia was 1.73 (95%CI 1.69-1.77). Z-GRS excluding APOE also increased dementia risk (OR 1.21 per SD increase, 95% CI 1.18-1.24) and there was no evidence that ethnicity modified this association. Prediction of secondary outcomes was less robust in those not of European ancestry when APOE was excluded from the GRS. INTERPRETATION: z-GRS derived from studies in people of European ancestry can be used to quantify genetic risk in people from more diverse ancestry groups. Urgent work is needed to include people from diverse ancestries in future genetic risk studies to make this field more inclusive.
date: 2022-12-07
date_type: published
publisher: Public Library of Science (PLoS)
official_url: https://doi.org/10.1371/journal.pone.0277378
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1995236
doi: 10.1371/journal.pone.0277378
medium: Electronic-eCollection
pii: PONE-D-22-19235
lyricists_name: Bass, Nicholas James
lyricists_name: Kuchenbaecker, Karoline
lyricists_name: Mukadam, Naaheed
lyricists_id: NJBAS95
lyricists_id: KBEKK98
lyricists_id: NMUKA20
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
funding_acknowledgements: AS-SF-18b-001 [Alzheimer's Society]
full_text_status: public
publication: PLoS One
volume: 17
number: 12
article_number: e0277378
event_location: United States
issn: 1932-6203
citation:        Mukadam, Naaheed;    Giannakopoulou, Olga;    Bass, Nick;    Kuchenbaecker, Karoline;    McQuillin, Andrew;      (2022)    Genetic risk scores and dementia risk across different ethnic groups in UK Biobank.                   PLoS One , 17  (12)    , Article e0277378.  10.1371/journal.pone.0277378 <https://doi.org/10.1371/journal.pone.0277378>.       Green open access   
 
document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10161825/1/journal.pone.0277378.pdf