Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes
(2022) In Genes 13(5).- Abstract
(1) Autoantibodies to the leucine variant of neuropeptide Y (NPY-LA) have been found in individuals with type 1 diabetes (T1D). We investigated the association between the levels of NPY-LA and single nucleotide polymorphisms (SNP) to better understand the genetic regulatory mechanisms of autoimmunity in T1D and the functional impacts of increased NPY-LA levels. (2) NPY-LA measurements from serum and SNP genotyping were done on 560 newly diagnosed individuals with T1D. SNP imputation with the 1000 Genomes reference panel was followed by an association analysis between the SNPs and measured NPY-LA levels. Additionally, functional enrichment and pathway analyses were done. (3) Three loci (DGKH, DCAF5, and LINC02261) were associated with... (More)
(1) Autoantibodies to the leucine variant of neuropeptide Y (NPY-LA) have been found in individuals with type 1 diabetes (T1D). We investigated the association between the levels of NPY-LA and single nucleotide polymorphisms (SNP) to better understand the genetic regulatory mechanisms of autoimmunity in T1D and the functional impacts of increased NPY-LA levels. (2) NPY-LA measurements from serum and SNP genotyping were done on 560 newly diagnosed individuals with T1D. SNP imputation with the 1000 Genomes reference panel was followed by an association analysis between the SNPs and measured NPY-LA levels. Additionally, functional enrichment and pathway analyses were done. (3) Three loci (DGKH, DCAF5, and LINC02261) were associated with NPY-LA levels (p-value < 1.5 × 10−6), which indicates an association with neurologic and vascular disorders. SNPs associated with variations in expression levels were found in six genes (including DCAF5). The pathway analysis showed that NPY-LA was associated with changes in gene tran-scription, protein modification, immunological functions, and the MAPK pathway. (4) Conclu-sively, we found NPY-LA to be significantly associated with three loci (DGKH, DCAF5, and LINC02261), and based on our findings we hypothesize that the presence of NPY-LA is associated with the regulation of the immune system and possibly neurologic and vascular disorders.
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- author
- Mansachs, Sara Juul ; Villumsen, Sofie Olund ; Johannesen, Jesper ; Lind, Alexander LU ; Kaur, Simranjeet and Pociot, Flemming LU
- organization
- publishing date
- 2022-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- autoimmunity, genetic regulatory mechanisms, GWAS, minor autoantigen, NPY-L autoantibodies, type 1 diabetes
- in
- Genes
- volume
- 13
- issue
- 5
- article number
- 869
- publisher
- MDPI AG
- external identifiers
-
- pmid:35627254
- scopus:85130368142
- ISSN
- 2073-4425
- DOI
- 10.3390/genes13050869
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
- id
- bacbeb2f-b8f4-4ca0-bafd-94a9dc3f73e5
- date added to LUP
- 2022-12-08 11:19:19
- date last changed
- 2024-09-19 02:07:13
@article{bacbeb2f-b8f4-4ca0-bafd-94a9dc3f73e5, abstract = {{<p>(1) Autoantibodies to the leucine variant of neuropeptide Y (NPY-LA) have been found in individuals with type 1 diabetes (T1D). We investigated the association between the levels of NPY-LA and single nucleotide polymorphisms (SNP) to better understand the genetic regulatory mechanisms of autoimmunity in T1D and the functional impacts of increased NPY-LA levels. (2) NPY-LA measurements from serum and SNP genotyping were done on 560 newly diagnosed individuals with T1D. SNP imputation with the 1000 Genomes reference panel was followed by an association analysis between the SNPs and measured NPY-LA levels. Additionally, functional enrichment and pathway analyses were done. (3) Three loci (DGKH, DCAF5, and LINC02261) were associated with NPY-LA levels (p-value < 1.5 × 10<sup>−6</sup>), which indicates an association with neurologic and vascular disorders. SNPs associated with variations in expression levels were found in six genes (including DCAF5). The pathway analysis showed that NPY-LA was associated with changes in gene tran-scription, protein modification, immunological functions, and the MAPK pathway. (4) Conclu-sively, we found NPY-LA to be significantly associated with three loci (DGKH, DCAF5, and LINC02261), and based on our findings we hypothesize that the presence of NPY-LA is associated with the regulation of the immune system and possibly neurologic and vascular disorders.</p>}}, author = {{Mansachs, Sara Juul and Villumsen, Sofie Olund and Johannesen, Jesper and Lind, Alexander and Kaur, Simranjeet and Pociot, Flemming}}, issn = {{2073-4425}}, keywords = {{autoimmunity; genetic regulatory mechanisms; GWAS; minor autoantigen; NPY-L autoantibodies; type 1 diabetes}}, language = {{eng}}, number = {{5}}, publisher = {{MDPI AG}}, series = {{Genes}}, title = {{Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes}}, url = {{http://dx.doi.org/10.3390/genes13050869}}, doi = {{10.3390/genes13050869}}, volume = {{13}}, year = {{2022}}, }