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Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes

Mansachs, Sara Juul ; Villumsen, Sofie Olund ; Johannesen, Jesper ; Lind, Alexander LU ; Kaur, Simranjeet and Pociot, Flemming LU (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
; ; ; ; and
organization
publishing date
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
  • scopus:85130368142
  • pmid:35627254
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
2024-05-29 16:01:44
@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 &lt; 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}},
}