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[Preprint]. 2023 Feb 5:2023.02.03.526066.
doi: 10.1101/2023.02.03.526066.

Leveraging type 1 diabetes human genetic and genomic data in the T1D Knowledge Portal

Parul Kudtarkar  1 , Maria C Costanzo  2   3 , Ying Sun  1 , Dongkeun Jang  2   3 , Ryan Koesterer  2   3 , Josyf C Mychaleckyj  4 , Uma Nayak  4 , Suna Onengut-Gumuscu  4 , Stephen S Rich  4 , Jason A Flannick  2   3   5   6 , Kyle J Gaulton  1 , Noël P Burtt  2   3
Affiliations

Leveraging type 1 diabetes human genetic and genomic data in the T1D Knowledge Portal

Parul Kudtarkar et al. bioRxiv. .

Update in

Abstract

Translating genetic discoveries for type 1 diabetes (T1D) into mechanistic insight can reveal novel biology and therapeutic targets but remains a major challenge. We developed the T1D Knowledge Portal (T1DKP), a disease-specific resource of genetic and functional annotation data that enables users to develop hypotheses for T1D-based research and target discovery. The T1DKP can be used to query genes and genomic regions for genetic associations, identify epigenomic features, access results of bioinformatic analyses, and obtain expert-curated resources. The T1DKP is available at http://t1d.hugeamp.org .

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Figures

Figure 1.
Figure 1.. Data content of the T1DKP.
The T1DKP provides genetic and genomic data, pre-computed bioinformatics results, and curated resources such as candidate effector gene lists to the T1D community.
Figure 2.
Figure 2.. Distilled evidence supporting T1D candidate genes in the T1DKP.
The T1DKP provides distillations of human genetic results for researchers who are not experts in human genetics. (A) The summary page for the CTLA4 gene provides evidence that this gene affects T1D risk, including results providing ‘very strong’ support from the HuGE calculator (Dornbos et al) and strong evidence for T1D association from MAGMA analyses (de Leeuw et al). (B) A ‘T1D effector genes’ list (Onengut-Gumuscu and Rich) predicts CTLA4 as a ‘causal’ gene for T1D based on genetic, perturbational, and gene regulatory evidence.
Figure 3.
Figure 3.. Predicting causal mechanisms at T1D risk loci in the T1DKP.
Predicting causal mechanisms at the 6q15 locus. (top) Prioritizing variants with evidence for affecting T1D risk based on significant association and 99% credible sets. (middle) Prioritizing variants overlapping cCREs active in T1D-enriched cell types and tissues. (bottom) Prioritizing genes linked to variants in cCREs in specific cell types and tissues. From these analyses two variants are predicted as causal candidates for T1D risk at this locus, which are linked to multiple candidate genes including BACH2 in immune cells.
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References

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