HLA-associated type 1 diabetes in world populations

Project name: HLA-associated type 1 diabetes in world populations

Project leader(s): J. Noble

Detailed project description:

HLA association with type 1 diabetes has been studied by both individual groups and large consortia for more than 40 years, yet a dearth of information still exists in populations other than those of European descent. We have collected a set of samples, including 100 T1D patients and 200 controls per country, from six under-resourced countries. In this project, we propose to:

  1. Generate 11-locus, whole-gene HLA genotyping data on existing samples, including Azerbaijan, Bangladesh, Haiti, Mali, Pakistan, and Sudan.
  2. Invite submission of samples from additional countries for genotyping.
  3. Invite submission of existing HLA NGS data from other countries as appropriate.
  4. Analyze T1D association for each population separately.
  5. Perform meta-analysis of all data at both allele and amino acid level.

Preliminary, moderate resolution data for DRB1 have shown that the T1D associated alleles vary among countries and that geographic proximity does not necessarily correlate with HLA-associated T1D genetic risk. We wish to extend these data to include all classical HLA loci with high-resolution, whole gene HLA genotyping data.

Milestones in years:

2019: Assemble existing and begin collecting new samples for genotyping. Collect existing data where appropriately generated.

2020: Begin genotyping and continue collection through June. Continue genotyping until December. Perform single population analyses as data are available.

2021: Complete single population analyses and perform meta-analyses

Patient/sample description (if applicable, details, inclusion/exclusion criteria):

Patients and controls from under-studied countries.

Patients: Youth with diagnosis of type 1 diabetes. Exclude known type 2 diabetes, MODY, other forms of diabetes.

Controls: 1) any age, both parents born in country of interest (no recent immigrants), no diabetes or relative with diabetes, unrelated to each other. Alternatively, affected family-based controls from family data.

Data required (number, type of data, inclusion/exclusion criteria):

11-locus, whole gene NGS-based HLA genotyping data.

Samples required (if applicable, number, type of samples, inclusion/exclusion criteria):

Ideally, at least 100 patients and 100 controls from each population, as described above.

Reagents/additional assays required:

DNA collection cards for new collections

DNA preparation reagents for new collections

NGS “whole gene” genotyping reagents for all samples

Data infrastructure required:

Consistent reporting of at least 2 and up to 4-field allele designations.