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. 2023 Aug 10;21(8):e3002233.
doi: 10.1371/journal.pbio.3002233. eCollection 2023 Aug.

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. PLoS Biol. .

Abstract

To address the challenge of translating genetic discoveries for type 1 diabetes (T1D) into mechanistic insight, we have developed the T1D Knowledge Portal (T1DKP), an open-access resource for hypothesis development and target discovery in T1D.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: KG holds stock in Neurocrine biosciences and has done consulting for Genentech.

Figures

Fig 1
Fig 1. Data content of the T1DKP.
The T1DKP provides genetic and genomic data, pre-computed bioinformatics results, and expert-curated resources such as candidate gene lists to the T1D community.
Fig 2
Fig 2. Distilled evidence supporting T1D variants and candidate genes in the T1DKP.
The T1DKP provides distillations of human genetic results for researchers. (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 and strong evidence for T1D association from MAGMA. (B) A “T1D effector genes” list predicts CTLA4 as a “causal” gene for T1D based on genetic, perturbation, and gene regulatory evidence. (C) 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, 2 variants are predicted as causal candidates for T1D at this locus, which are linked to multiple candidate genes including BACH2 in immune cells.
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