TY - JOUR

T1 - Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes

AU - Mansachs, Sara Juul

AU - Villumsen, Sofie Olund

AU - Johannesen, Jesper

AU - Lind, Alexander

AU - Kaur, Simranjeet

AU - Pociot, Flemming

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - (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.

AB - (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.

KW - autoimmunity

KW - genetic regulatory mechanisms

KW - GWAS

KW - minor autoantigen

KW - NPY-L autoantibodies

KW - type 1 diabetes

U2 - 10.3390/genes13050869

DO - 10.3390/genes13050869

M3 - Journal article

C2 - 35627254

AN - SCOPUS:85130368142

VL - 13

JO - Genes

JF - Genes

SN - 2073-4425

IS - 5

M1 - 869

ER -