The value of genetic data from 665,460 individuals in managing iron deficiency anaemia and suitability to donate blood.
GWAS
Hb-deferral
PRS
genetic risk
iron deficiency anaemia
statistical inference
Journal
Vox sanguinis
ISSN: 1423-0410
Titre abrégé: Vox Sang
Pays: England
ID NLM: 0413606
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
revised:
15
08
2023
received:
24
01
2023
accepted:
30
10
2023
medline:
29
11
2023
pubmed:
29
11
2023
entrez:
29
11
2023
Statut:
aheadofprint
Résumé
Although the genetic determinants of haemoglobin and ferritin have been widely studied, those of the clinically and globally relevant iron deficiency anaemia (IDA) and deferral due to hypohaemoglobinemia (Hb-deferral) are unclear. In this investigation, we aimed to quantify the value of genetic information in predicting IDA and Hb-deferral. We analysed genetic data from up to 665,460 participants of the FinnGen, Blood Service Biobank and UK Biobank, and used INTERVAL (N = 39,979) for validation. We performed genome-wide association studies (GWASs) of IDA and Hb-deferral and utilized publicly available genetic associations to compute polygenic scores for IDA, ferritin and Hb. We fitted models to estimate the effect sizes of these polygenic risk scores (PRSs) on IDA and Hb-deferral risk while accounting for the individual's age, sex, weight, height, smoking status and blood donation history. Significant variants in GWASs of IDA and Hb-deferral appear to be a small subset of variants associated with ferritin and Hb. Effect sizes of genetic predictors of IDA and Hb-deferral are similar to those of age and weight which are typically used in blood donor management. A total genetic score for Hb-deferral was estimated for each individual. The odds ratio estimate between first decile against that at ninth decile of total genetic score distribution ranged from 1.4 to 2.2. The value of genetic data in predicting IDA or suitability to donate blood appears to be on a practically useful level.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
Although the genetic determinants of haemoglobin and ferritin have been widely studied, those of the clinically and globally relevant iron deficiency anaemia (IDA) and deferral due to hypohaemoglobinemia (Hb-deferral) are unclear. In this investigation, we aimed to quantify the value of genetic information in predicting IDA and Hb-deferral.
MATERIALS AND METHODS
METHODS
We analysed genetic data from up to 665,460 participants of the FinnGen, Blood Service Biobank and UK Biobank, and used INTERVAL (N = 39,979) for validation. We performed genome-wide association studies (GWASs) of IDA and Hb-deferral and utilized publicly available genetic associations to compute polygenic scores for IDA, ferritin and Hb. We fitted models to estimate the effect sizes of these polygenic risk scores (PRSs) on IDA and Hb-deferral risk while accounting for the individual's age, sex, weight, height, smoking status and blood donation history.
RESULTS
RESULTS
Significant variants in GWASs of IDA and Hb-deferral appear to be a small subset of variants associated with ferritin and Hb. Effect sizes of genetic predictors of IDA and Hb-deferral are similar to those of age and weight which are typically used in blood donor management. A total genetic score for Hb-deferral was estimated for each individual. The odds ratio estimate between first decile against that at ninth decile of total genetic score distribution ranged from 1.4 to 2.2.
CONCLUSION
CONCLUSIONS
The value of genetic data in predicting IDA or suitability to donate blood appears to be on a practically useful level.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : BHF Programme Grant (RG/18/13/33946)
Informations de copyright
© 2023 Finnish Red Cross Blood Service and The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.
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