Phasing Classical HLA Alleles

Question

[jacob]

Hello,

I am trying to calculate "Type 1 Diabetes Genetic Risk Score 2" for participants in the UK Biobank. This algorithm takes into account HLA-DR-DQ haplotypes haplotypes to determine risk via DQA1-DQB1 alleles, meaning that classical HLA alleles must be phased in order to compute the score. However, UK Biobank HLA imputation values are not phased and data for parent haplotypes is not available.

Would anyone be able to point me to a software that would be able to phase the classical HLA alleles based on genotypes (i.e. if DQA1^501, DQA1^301, DQB1^201, and DQB1^302 are all present, the haplotypes are likely DQA1^501-DQB1^201 and DQA1^301-DQB1^302)? If not, can anyone share methodology for this can be done using population frequencies for known haplotypes?

Thank you for your help,

Jacob

PS: I used ^ instead of asterisks because the asterisks would not appear and would instead set the font to italics.

Here is the reference for the risk score I wish to compute:

Sharp SA, Rich SS, Wood AR, Jones SE, Beaumont RN, Harrison JW, Schneider DA, Locke JM, Tyrrell J, Weedon MN, Hagopian WA, Oram RA. Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis. Diabetes Care. 2019 Feb;42(2):200-207. doi: 10.2337/dc18-1785. PMID: 30655379; PMCID: PMC6341291.

Answer 1

[Ming Tommy Tang]

This paper was just out Tutorial: a statistical genetics guide to identifying HLA alleles driving complex disease https://www.nature.com/articles/s41596-023-00853-4

Also, take a look at https://github.com/mourisl/T1K this works with raw sequencing data

Answer 2

[Trombone Engineer]

I have had success with HLA-HD as well as xHLA software for HLA typing of Illumina WGS data. HLA-HD took more effort to get to successfully run, as well as a lot more computation time than xHLA. Meanwhile, xHLA was pretty fast to run as well to figure out. Accuracy has been harder for me to assess outside of benchmarking papers of HLA typing bioinformatics, but there is literature that covers both of these tools and more.

Answer 3

[4galaxy77]

The Michigan Imputation Server does HLA imputation and phasing.