Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes
<b>(1)</b> 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 mechan...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/13/5/869 |
| _version_ | 1797499596451086336 |
|---|---|
| author | Sara Juul Mansachs Sofie Olund Villumsen Jesper Johannesen Alexander Lind Simranjeet Kaur Flemming Pociot |
| author_facet | Sara Juul Mansachs Sofie Olund Villumsen Jesper Johannesen Alexander Lind Simranjeet Kaur Flemming Pociot |
| author_sort | Sara Juul Mansachs |
| collection | DOAJ |
| description | <b>(1)</b> 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. <b>(2)</b> 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. <b>(3)</b> Three loci (<i>DGKH</i>, <i>DCAF5</i>, and <i>LINC02261</i>) were associated with NPY-LA levels (<i>p</i>-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 <i>DCAF5</i>). The pathway analysis showed that NPY-LA was associated with changes in gene transcription, protein modification, immunological functions, and the MAPK pathway. <b>(4)</b> Conclusively, we found NPY-LA to be significantly associated with three loci (<i>DGKH</i>, <i>DCAF5</i>, and <i>LINC02261</i>), 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. |
| first_indexed | 2024-03-10T03:49:40Z |
| format | Article |
| id | doaj.art-d16792c344d847c091e07117f43ae5a4 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T03:49:40Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-d16792c344d847c091e07117f43ae5a42023-11-23T11:10:47ZengMDPI AGGenes2073-44252022-05-0113586910.3390/genes13050869Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 DiabetesSara Juul Mansachs0Sofie Olund Villumsen1Jesper Johannesen2Alexander Lind3Simranjeet Kaur4Flemming Pociot5Department of Children Adolescents, Copenhagen University Hospital Herlev, 2730 Herlev, DenmarkTranslational Type 1 Diabetes Research, Steno Diabetes Center Copenhagen, 2739 Herlev, DenmarkDepartment of Children Adolescents, Copenhagen University Hospital Herlev, 2730 Herlev, DenmarkDepartment of Clinical Sciences, Lund University CRC, Skåne University Hospital, 200 49 Malmo, SwedenTranslational Type 1 Diabetes Research, Steno Diabetes Center Copenhagen, 2739 Herlev, DenmarkDepartment of Children Adolescents, Copenhagen University Hospital Herlev, 2730 Herlev, Denmark<b>(1)</b> 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. <b>(2)</b> 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. <b>(3)</b> Three loci (<i>DGKH</i>, <i>DCAF5</i>, and <i>LINC02261</i>) were associated with NPY-LA levels (<i>p</i>-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 <i>DCAF5</i>). The pathway analysis showed that NPY-LA was associated with changes in gene transcription, protein modification, immunological functions, and the MAPK pathway. <b>(4)</b> Conclusively, we found NPY-LA to be significantly associated with three loci (<i>DGKH</i>, <i>DCAF5</i>, and <i>LINC02261</i>), 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.https://www.mdpi.com/2073-4425/13/5/869NPY-L autoantibodiesminor autoantigenautoimmunitytype 1 diabetesgenetic regulatory mechanismsGWAS |
| spellingShingle | Sara Juul Mansachs Sofie Olund Villumsen Jesper Johannesen Alexander Lind Simranjeet Kaur Flemming Pociot Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes Genes NPY-L autoantibodies minor autoantigen autoimmunity type 1 diabetes genetic regulatory mechanisms GWAS |
| title | Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes |
| title_full | Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes |
| title_fullStr | Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes |
| title_full_unstemmed | Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes |
| title_short | Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes |
| title_sort | genetic variants associated with neuropeptide y autoantibody levels in newly diagnosed individuals with type 1 diabetes |
| topic | NPY-L autoantibodies minor autoantigen autoimmunity type 1 diabetes genetic regulatory mechanisms GWAS |
| url | https://www.mdpi.com/2073-4425/13/5/869 |
| work_keys_str_mv | AT sarajuulmansachs geneticvariantsassociatedwithneuropeptideyautoantibodylevelsinnewlydiagnosedindividualswithtype1diabetes AT sofieolundvillumsen geneticvariantsassociatedwithneuropeptideyautoantibodylevelsinnewlydiagnosedindividualswithtype1diabetes AT jesperjohannesen geneticvariantsassociatedwithneuropeptideyautoantibodylevelsinnewlydiagnosedindividualswithtype1diabetes AT alexanderlind geneticvariantsassociatedwithneuropeptideyautoantibodylevelsinnewlydiagnosedindividualswithtype1diabetes AT simranjeetkaur geneticvariantsassociatedwithneuropeptideyautoantibodylevelsinnewlydiagnosedindividualswithtype1diabetes AT flemmingpociot geneticvariantsassociatedwithneuropeptideyautoantibodylevelsinnewlydiagnosedindividualswithtype1diabetes |