Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design
<b>Background/Objectives</b>: Genes and environments were transmitted across generations. Parents’ genetics influence the environments of their offspring; these two modes of inheritance can produce a genetic nurture effect, also known as indirect genetic effects. Such indirect effects ma...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/1/120 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588981401812992 |
|---|---|
| author | Xiaoyi Li Zechen Zhou Yujia Ma Kexin Ding Han Xiao Tao Wu Dafang Chen Yiqun Wu |
| author_facet | Xiaoyi Li Zechen Zhou Yujia Ma Kexin Ding Han Xiao Tao Wu Dafang Chen Yiqun Wu |
| author_sort | Xiaoyi Li |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Genes and environments were transmitted across generations. Parents’ genetics influence the environments of their offspring; these two modes of inheritance can produce a genetic nurture effect, also known as indirect genetic effects. Such indirect effects may partly account for estimated genetic variance in T2D. However, the well-established specific genetic risk factors about genetic nurture effect for T2D are not fully understood. This study aimed to investigate the genetic nurture effect on type 2 diabetes and reveal the potential underlying mechanism using publicly available data. <b>Methods</b>: Whole-genome genotyping data of 881 offspring and/or their parents were collected. We assessed SNP-level, gene-based, and pathway-based associations for different types of genetic effects. <b>Results</b>: Rs3805116 (β: 0.54, <i>p</i> = 4.39 × 10<sup>−8</sup>) was significant for paternal genetic nurture effects. <i>MRPS33</i> (<i>p</i> = 1.58 × 10<sup>−6</sup>), <i>PIH1D2</i> (<i>p</i> = 6.76 × 10<sup>−7</sup>), and <i>SD1HD</i> (<i>p</i> = 2.67 × 10<sup>−6</sup>) revealed significantly positive paternal genetic nurture effects. Five ontologies were identified as enrichment in both direct and indirect genetic effects, including flavonoid metabolic process and antigen processing and presentation via the MHC class Ib pathway. Two pathways were only enriched in paternal genetic nurture effects, including the transforming growth factor beta pathway. Tissue enrichment of type 2 diabetes-associated genes on different genetic effect types was performed using publicly available gene expression data from the Human Protein Atlas database. We observed significant gene enrichment in paternal genetic nurture effects in the gallbladder, smooth muscle, and adrenal gland tissues. <b>Conclusions</b>: <i>MRPS33</i>, <i>PIH1D2</i>, and <i>SD1HD</i> are associated with increased T2D risk through the environment influenced by paternal genotype, suggesting a novel perspective on paternal contributions to the T2D predisposition. |
| format | Article |
| id | doaj-art-74c21aba77774467b7f061bc752a86ad |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-74c21aba77774467b7f061bc752a86ad2025-01-24T13:24:05ZengMDPI AGBiomedicines2227-90592025-01-0113112010.3390/biomedicines13010120Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based DesignXiaoyi Li0Zechen Zhou1Yujia Ma2Kexin Ding3Han Xiao4Tao Wu5Dafang Chen6Yiqun Wu7Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaThe Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China<b>Background/Objectives</b>: Genes and environments were transmitted across generations. Parents’ genetics influence the environments of their offspring; these two modes of inheritance can produce a genetic nurture effect, also known as indirect genetic effects. Such indirect effects may partly account for estimated genetic variance in T2D. However, the well-established specific genetic risk factors about genetic nurture effect for T2D are not fully understood. This study aimed to investigate the genetic nurture effect on type 2 diabetes and reveal the potential underlying mechanism using publicly available data. <b>Methods</b>: Whole-genome genotyping data of 881 offspring and/or their parents were collected. We assessed SNP-level, gene-based, and pathway-based associations for different types of genetic effects. <b>Results</b>: Rs3805116 (β: 0.54, <i>p</i> = 4.39 × 10<sup>−8</sup>) was significant for paternal genetic nurture effects. <i>MRPS33</i> (<i>p</i> = 1.58 × 10<sup>−6</sup>), <i>PIH1D2</i> (<i>p</i> = 6.76 × 10<sup>−7</sup>), and <i>SD1HD</i> (<i>p</i> = 2.67 × 10<sup>−6</sup>) revealed significantly positive paternal genetic nurture effects. Five ontologies were identified as enrichment in both direct and indirect genetic effects, including flavonoid metabolic process and antigen processing and presentation via the MHC class Ib pathway. Two pathways were only enriched in paternal genetic nurture effects, including the transforming growth factor beta pathway. Tissue enrichment of type 2 diabetes-associated genes on different genetic effect types was performed using publicly available gene expression data from the Human Protein Atlas database. We observed significant gene enrichment in paternal genetic nurture effects in the gallbladder, smooth muscle, and adrenal gland tissues. <b>Conclusions</b>: <i>MRPS33</i>, <i>PIH1D2</i>, and <i>SD1HD</i> are associated with increased T2D risk through the environment influenced by paternal genotype, suggesting a novel perspective on paternal contributions to the T2D predisposition.https://www.mdpi.com/2227-9059/13/1/120type 2 diabetes mellitusgenetic susceptibilitygenegenetic nurture effectpaternal nurture effect |
| spellingShingle | Xiaoyi Li Zechen Zhou Yujia Ma Kexin Ding Han Xiao Tao Wu Dafang Chen Yiqun Wu Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design Biomedicines type 2 diabetes mellitus genetic susceptibility gene genetic nurture effect paternal nurture effect |
| title | Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design |
| title_full | Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design |
| title_fullStr | Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design |
| title_full_unstemmed | Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design |
| title_short | Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design |
| title_sort | genetic nurture effects on type 2 diabetes among chinese han adults a family based design |
| topic | type 2 diabetes mellitus genetic susceptibility gene genetic nurture effect paternal nurture effect |
| url | https://www.mdpi.com/2227-9059/13/1/120 |
| work_keys_str_mv | AT xiaoyili geneticnurtureeffectsontype2diabetesamongchinesehanadultsafamilybaseddesign AT zechenzhou geneticnurtureeffectsontype2diabetesamongchinesehanadultsafamilybaseddesign AT yujiama geneticnurtureeffectsontype2diabetesamongchinesehanadultsafamilybaseddesign AT kexinding geneticnurtureeffectsontype2diabetesamongchinesehanadultsafamilybaseddesign AT hanxiao geneticnurtureeffectsontype2diabetesamongchinesehanadultsafamilybaseddesign AT taowu geneticnurtureeffectsontype2diabetesamongchinesehanadultsafamilybaseddesign AT dafangchen geneticnurtureeffectsontype2diabetesamongchinesehanadultsafamilybaseddesign AT yiqunwu geneticnurtureeffectsontype2diabetesamongchinesehanadultsafamilybaseddesign |