ABO

ABO Blood type analysis

We developed HLA/ABO frequency map for visualization of the ABO bloodtype and HLA allelotype frequency data.

Summary

Recently, Zhao et al.[1] reported ABO blood type frequency differences between the COVID-19 patients and the control population. To replicate their findings using an independent set of unrelated individuals, and to provide a reference panel for ABO blood type frequencies across diverse populations, we aggregated the ABO blood type information. Given that the haplotype at ABO locus that define the four major ABO antigen is tagged by 3 SNPs[2,3], we extracted the genotype information at those variants, computed the frequencies of the haplotypes and the blood types across 9 population groups (White British, Non-British white, African, South Asian, East Asian, self-reported Chinese, self-reported Indian, self-reported Pakistani, and self-reported Bangladeshi).

Please check out initial draft of host genetics of COVID-19, Initial review and analysis of COVID-19 host genetics and associated phenotypes for more about the analysis.

ABO allele	rs8176746	rs687289	rs507666
A1	G	A	A
A2	G	A	G
B	T	A	G
O	G	G	G

Table: the list of tag SNPs used for the ABO blood type analysis.

List of files in this directory

Results files

• ABO_external_studies_freq.tsv: this file contains the ABO frequency information from a previous study[1].
• ABO_UKB_freq.tsv: this file contains our estimates of the frequencies of ABO blood types (haplotype, ABO_allele, and ABO_allele_full columns) in population groups (population column) in UK Biobank. The n column is the number of individuals, frequency is the estimated frequency, and SE represents the standard error.
• ABO_combined_freq.tsv: this file contains the ABO blood frequency information for both external studies and UK Biobank.
• ABO_OR.tsv: this file contains the results of frequency comparison.

New files (still part of the internal testing)

We have estimates of the ABO blood type frequency estimate based on the haplotypes at the ABO locus. For this analysis, we used a LD proxy, rs687621 (9:136137065:A:G), instead of rs687289 (9:136137106:G:A) on the phased array genotyped dataset in UK Biobank. The r2 between those two variants were 0.99319 in White British.

ABO allele	rs8176746	rs687621	rs507666
A1	G	G	A
A2	G	G	G
B	T	G	G
O	G	A	G

The results of ABO blod type frequency estimates are written in the following two files:

• ABO.UKB.population.freq.tsv
• ABO.UKB.country_of_birth.freq.tsv

The first column is population or country of birth, the second column is the number of individuals in that group, and the third to 6th columns (freq_A, freq_B, freq_AB, and freq_O) are the formatted frequency estimates with 95% confidence interval, followed by 3 sets of 4 columns: n_<ABO bood type> (the number of individuals), f_<ABO bood type> (frequency), and ci_<ABO bood type> (the length of the confidence interval). The 95% confidence intervals are computed based on Binomial model (CI = 1.96 * sqrt((f * (1-f))/N)) and [f_<ABO bood type> - ci_<ABO bood type>, f_<ABO bood type> + ci_<ABO bood type>] should give you the CI.

Scripts and notebook

• 1_prep_plink_data.sh: we extract the three variants (defined in 1_prep_plink_data.var.lst) from the genotype dataset and prepare files for plink version 1.07.
• 2_hap_freq.sh: phase (estimate the haplotype) and estimate their frequencies with plink 1.07.
• 3_compute_hap_freq.R and 3_compute_hap_freq.sh: compute the estimated blood type frequencies.
• 4_ABO_freq_combine.R: combine the estimated blood type frequencies into a file (ABO_UKB_freq.tsv).
• 5_ABO_comparison.ipynb: compare the ABO blood type frequencies. The results are written to ABO_OR.tsv.
• sample_qc_v3.2.self_reported_pop_def.ipynb: this notebook illustrates our procedure to define additional population groups of unrelated invidiuals in UK Biobank using the self-reported ethnicity data. The population size is recorded in UKB_population_n.tsv.
• ABO_functions.R: this file contains functions used in the R scripts.

Acknowledgement

We thank Mike Inouye (@minouye271) for pointing the reference[3].

Reference

1. Zhao, J. et al. Relationship between the ABO Blood Group and the COVID-19 Susceptibility. medRxiv 2020.03.11.20031096 (2020).
2. Paré, G. et al. Novel Association of ABO Histo-Blood Group Antigen with Soluble ICAM-1: Results of a Genome-Wide Association Study of 6,578 Women. PLOS Genetics 4, e1000118 (2008).
3. Johansson, Å., Alfredsson, J., Eriksson, N., Wallentin, L. & Siegbahn, A. Genome-Wide Association Study Identifies That the ABO Blood Group System Influences Interleukin-10 Levels and the Risk of Clinical Events in Patients with Acute Coronary Syndrome. PLOS ONE 10, e0142518 (2015).
4. Purcell, S. et al. PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. The American Journal of Human Genetics 81, 559–575 (2007).