Scholarlink

Aims <p>This study evaluates the contribution of common variants in Maturity-Onset Diabetes of the Young (MODY) genes on type 1 diabetes (T1D), using a polygenic score (PGS) approach.</p> Methods <p>485 children and youth diagnosed with T1D from at least 1 year and 271 healthy controls (HC) were recruited. Personal information (i.e. age, sex, height, weight) were collected for each participant, and clinical information (i.e. age at diagnosis, disease duration, presence of autoantibodies and ketoacidosis at onset (DKA)) were also obtained for T1D subjects.</p> <p>Participants were genotyped using Illumina Infinium Global Screening Array. PGS based on Single Nucleotide Polymorphisms (SNPs) in 16 MODY genes were developed. The association of this PGS with T1D susceptibility and clinical disease characteristics was assessed by regression analysis.</p> Results <p>A PGS including 335 SNPs in MODY genes discriminates T1D from HC (AUC = 60.1%, AIC = 787.6). This PGS was significantly higher in T1D compared to HC (p-value = 0.0004, pseudo-R2 = 2.85%). Moreover, regression analysis between PGS and T1D clinical characteristics showed higher PGS values in T1D subjects with zinc transporter 8 autoantibodies (ZnT8A) compared with T1D subjects without ZnT8A (p-value = 0.04). A similar trend was also observed for antibodies directed against glutamic acid decarboxylase (GADA), although the association did not reach statistical significance (p-value = 0.06).</p> Conclusions <p>Our study suggests that a polygenic approach based on MODY genes may discriminate T1D from HC and may contribute to patient stratification, helping to better understand T1D heterogeneity.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Polygenic score from MODY genes is associated with type 1 diabetes and disease characteristics

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月20日

查看全文
  • Eulalia Catamo,
  • Andrea Conti,
  • Roberto Franceschi,
  • Klemen Dovc,
  • Camilla Morosini,
  • Davide Tinti,
  • Luana Aldegheri,
  • Stefania Cappellani,
  • Gianluca Tamaro,
  • Angela Zanfardino,
  • Elena Faleschini,
  • Ivana Rabbone,
  • Riccardo Bonfanti,
  • Tadej Battelino,
  • Dario Iafusco,
  • Gianluca Tornese,
  • Antonietta Robino

摘要

Aims

This study evaluates the contribution of common variants in Maturity-Onset Diabetes of the Young (MODY) genes on type 1 diabetes (T1D), using a polygenic score (PGS) approach.

Methods

485 children and youth diagnosed with T1D from at least 1 year and 271 healthy controls (HC) were recruited. Personal information (i.e. age, sex, height, weight) were collected for each participant, and clinical information (i.e. age at diagnosis, disease duration, presence of autoantibodies and ketoacidosis at onset (DKA)) were also obtained for T1D subjects.

Participants were genotyped using Illumina Infinium Global Screening Array. PGS based on Single Nucleotide Polymorphisms (SNPs) in 16 MODY genes were developed. The association of this PGS with T1D susceptibility and clinical disease characteristics was assessed by regression analysis.

Results

A PGS including 335 SNPs in MODY genes discriminates T1D from HC (AUC = 60.1%, AIC = 787.6). This PGS was significantly higher in T1D compared to HC (p-value = 0.0004, pseudo-R2 = 2.85%). Moreover, regression analysis between PGS and T1D clinical characteristics showed higher PGS values in T1D subjects with zinc transporter 8 autoantibodies (ZnT8A) compared with T1D subjects without ZnT8A (p-value = 0.04). A similar trend was also observed for antibodies directed against glutamic acid decarboxylase (GADA), although the association did not reach statistical significance (p-value = 0.06).

Conclusions

Our study suggests that a polygenic approach based on MODY genes may discriminate T1D from HC and may contribute to patient stratification, helping to better understand T1D heterogeneity.