TY - JOUR
T1 - Disparities in ABO blood type determination across diverse ancestries
T2 - a systematic review and validation in the All of Us Research Program
AU - Martinez, Kiana L.
AU - Klein, Andrew
AU - Martin, Jennifer R
AU - Sampson, Chinwuwanuju U.
AU - Giles, Jason B.
AU - Beck, Madison L.
AU - Bhakta, Krupa
AU - Quatraro, Gino
AU - Farol, Juvie
AU - Karnes, Jason H.
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: [email protected].
PY - 2024/12/1
Y1 - 2024/12/1
N2 - OBJECTIVES: ABO blood types have widespread clinical use and robust associations with disease. The purpose of this study is to evaluate the portability and suitability of tag single-nucleotide polymorphisms (tSNPs) used to determine ABO alleles and blood types across diverse populations in published literature. MATERIALS AND METHODS: Bibliographic databases were searched for studies using tSNPs to determine ABO alleles. We calculated linkage between tSNPs and functional variants across inferred continental ancestry groups from 1000 Genomes. We compared r2 across ancestry and assessed real-world consequences by comparing tSNP-derived blood types to serology in a diverse population from the All of Us Research Program. RESULTS: Linkage between functional variants and O allele tSNPs was significantly lower in African (median r2 = 0.443) compared to East Asian (r2 = 0.946, P = 1.1 × 10-5) and European (r2 = 0.869, P = .023) populations. In All of Us, discordance between tSNP-derived blood types and serology was high across all SNPs in African ancestry individuals and linkage was strongly correlated with discordance across all ancestries (ρ = -0.90, P = 3.08 × 10-23). DISCUSSION: Many studies determine ABO blood types using tSNPs. However, tSNPs with low linkage disequilibrium promote misinference of ABO blood types, particularly in diverse populations. We observe common use of inappropriate tSNPs to determine ABO blood type, particularly for O alleles and with some tSNPs mistyping up to 58% of individuals. CONCLUSION: Our results highlight the lack of transferability of tSNPs across ancestries and potential exacerbation of disparities in genomic research for underrepresented populations. This is especially relevant as more diverse cohorts are made publicly available.
AB - OBJECTIVES: ABO blood types have widespread clinical use and robust associations with disease. The purpose of this study is to evaluate the portability and suitability of tag single-nucleotide polymorphisms (tSNPs) used to determine ABO alleles and blood types across diverse populations in published literature. MATERIALS AND METHODS: Bibliographic databases were searched for studies using tSNPs to determine ABO alleles. We calculated linkage between tSNPs and functional variants across inferred continental ancestry groups from 1000 Genomes. We compared r2 across ancestry and assessed real-world consequences by comparing tSNP-derived blood types to serology in a diverse population from the All of Us Research Program. RESULTS: Linkage between functional variants and O allele tSNPs was significantly lower in African (median r2 = 0.443) compared to East Asian (r2 = 0.946, P = 1.1 × 10-5) and European (r2 = 0.869, P = .023) populations. In All of Us, discordance between tSNP-derived blood types and serology was high across all SNPs in African ancestry individuals and linkage was strongly correlated with discordance across all ancestries (ρ = -0.90, P = 3.08 × 10-23). DISCUSSION: Many studies determine ABO blood types using tSNPs. However, tSNPs with low linkage disequilibrium promote misinference of ABO blood types, particularly in diverse populations. We observe common use of inappropriate tSNPs to determine ABO blood type, particularly for O alleles and with some tSNPs mistyping up to 58% of individuals. CONCLUSION: Our results highlight the lack of transferability of tSNPs across ancestries and potential exacerbation of disparities in genomic research for underrepresented populations. This is especially relevant as more diverse cohorts are made publicly available.
KW - All of Us Research Program
KW - ABO blood type
KW - health disparities
KW - linkage
KW - tag single-nucleotide polymorphisms
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U2 - 10.1093/jamia/ocae161
DO - 10.1093/jamia/ocae161
M3 - Article
C2 - 38917427
AN - SCOPUS:85212457316
SN - 1067-5027
VL - 31
SP - 3022
EP - 3031
JO - Journal of the American Medical Informatics Association : JAMIA
JF - Journal of the American Medical Informatics Association : JAMIA
IS - 12
ER -