| Title: | Stratification of Type 2 Diabetes by Age of Diagnosis in the UK Biobank Reveals Subgroup-Specific Genetic Associations and Causal Risk Profiles |
| Journal: | Diabetes |
| Published: | 10 May 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33972266/ |
| DOI: | https://doi.org/10.2337/db20-0602 |
| URL: | https://diabetesjournals.org/diabetes/article-pdf/70/8/1816/629683/db200602.pdf |
| Citations: | 18 (11 in last 2 years) as of 8 Aug 2024 |
Publication 5778
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
The pathogenesis of type 2 diabetes (T2D) might change with increasing age. Here, we used a stratification based on age of diagnosis to gain insight into the genetics and causal risk factors of T2D across different age-groups. We performed genome-wide association studies (GWAS) on T2D and T2D subgroups based on age of diagnosis (<50, 50-60, 60-70, and >70 years) (total of 24,986 cases). As control subjects, participants were at least 70 years of age at the end of follow-up without developing T2D (N =187,130). GWAS identified 208 independent lead single nucleotide polymorphism (SNPs) mapping to 69 loci associated with T2D (P < 1.0e-8). Among others, SNPs mapped to CDKN2B-AS1 and multiple independent SNPs mapped to TCF7L2 were more strongly associated with cases diagnosed after age 70 years than with cases diagnosed before age 50 years. Based on the different case groups, we performed two-sample Mendelian randomization. Most notably, we observed that of the investigated risk factors, the association between BMI and T2D attenuated with increasing age of diagnosis. Collectively, our results indicate that stratification of T2D based on age of diag-nosis reveals subgroup-specific genetics and causal determinants, supporting the hypothesis that the pathogenesis of T2D changes with increasing age.</p>
16 Keywords
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Biological Specimen Banks
- Diabetes Mellitus, Type 2
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Genotype
- Humans
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Transcription Factor 7-Like 2 Protein
- United Kingdom
14 Authors
- Raymond Noordam
- Kristi Läll
- Roelof A.J. Smit
- Triin Laisk
- Andres Metspalu
- Tõnu Esko
- Lili Milani
- Ruth J.F. Loos
- Reedik Mägi
- Ko Willems van Dijk
- Diana van Heemst
- Andres Metspalu
- Tõnu Esko
- Lili Milani
Enabling scientific discoveries that improve human health