| 1. |
- Greenwald, WW, et al.
(författare)
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Pancreatic islet chromatin accessibility and conformation reveals distal enhancer networks of type 2 diabetes risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2078-
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants affecting pancreatic islet enhancers are central to T2D risk, but the gene targets of islet enhancer activity are largely unknown. We generate a high-resolution map of islet chromatin loops using Hi-C assays in three islet samples and use loops to annotate target genes of islet enhancers defined using ATAC-seq and published ChIP-seq data. We identify candidate target genes for thousands of islet enhancers, and find that enhancer looping is correlated with islet-specific gene expression. We fine-map T2D risk variants affecting islet enhancers, and find that candidate target genes of these variants defined using chromatin looping and eQTL mapping are enriched in protein transport and secretion pathways. At IGF2BP2, a fine-mapped T2D variant reduces islet enhancer activity and IGF2BP2 expression, and conditional inactivation of IGF2BP2 in mouse islets impairs glucose-stimulated insulin secretion. Our findings provide a resource for studying islet enhancer function and identifying genes involved in T2D risk.
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| 2. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 3. |
- Gorkin, Pamela, et al.
(författare)
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Thin sequences and the Gram matrix
- 2014
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Ingår i: Archiv der Mathematik. - : Springer Science and Business Media LLC. - 0003-889X .- 1420-8938. ; 103:1, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- We provide a new proof of Volberg's Theorem characterizing thin interpolating sequences as those for which the Gram matrix associated to the normalized reproducing kernels is a compact perturbation of the identity. In the same paper, Volberg characterized sequences for which the Gram matrix is a compact perturbation of a unitary as well as those for which the Gram matrix is a Schatten-2 class perturbation of a unitary operator. We extend this characterization from 2 to p, where 2 <= p <= infinity.
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| 4. |
- Gorkin, Pamela, et al.
(författare)
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Thin sequences and their role in H-p theory, model spaces, and uniform algebras
- 2015
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Ingår i: Revista Matemática Iberoamericana. - 2235-0616. ; 31:3, s. 841-864
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we revisit some facts about thin interpolating sequences in the unit disc from three perspectives: uniform algebras, model spaces, and H-p spaces. We extend the notion of asymptotic interpolation to H-p spaces, for 1 <= p <= infinity, providing several new ways to think about these sequences.
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