Genetic risk scores and dementia risk across different ethnic groups in UK Biobank

Genetic Risk Scores (GRS) for predicting dementia risk have mostly been used in people of European ancestry with limited testing in other ancestry groups. We conducted a logistic regression with all-cause dementia as the outcome and z-standardised GRS as the exposure across diverse ethnic groups. Th...

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Bibliographic Details
Published in:PloS one 2022-12, Vol.17 (12), p.e0277378-e0277378
Main Authors: Mukadam, Naaheed, Giannakopoulou, Olga, Bass, Nick, Kuchenbaecker, Karoline, McQuillin, Andrew
Format: Article
Language:English
Subjects:
Apolipoprotein E
Biobanks
Biological Specimen Banks
Biology and Life Sciences
Dementia
Dementia - epidemiology
Dementia - genetics
Dementia disorders
Diagnosis
Ethnic factors
Ethnic groups
Ethnicity
Frequency variation
Gene frequency
Genetic aspects
Genomes
Health aspects
Health risk assessment
Health risks
Hispanic Americans
Humans
Medicine and Health Sciences
Minority & ethnic groups
People and Places
Quality control
Risk
Risk Factors
Social Sciences
United Kingdom - epidemiology
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Summary:Genetic Risk Scores (GRS) for predicting dementia risk have mostly been used in people of European ancestry with limited testing in other ancestry groups. We conducted a logistic regression with all-cause dementia as the outcome and z-standardised GRS as the exposure across diverse ethnic groups. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0277378