Whole-exome and whole-genome sequencing of 1064 individuals with type 1 diabetes reveals novel genes for diabetic kidney disease
Authors' conclusion
Our sequencing-based meta-analysis revealed multiple genes, variants and regulatory regions that were suggestively associated with DKD. However, as no variant or gene reached genome-wide significance, further studies are needed to validate the findings.
Study context
- Population
- Individuals with T1D; Whole-exome sequencing (WES) in 498 and whole-genome sequencing (WGS) in 599after quality control
- Participants
- 1,064 individuals
- Comparison
- Diabetic kidney disease (DKD) vs normal albumin excretion despite long T1D duration
- DKDn = 541
- Normal albumin excretionn = 523reference
- Outcome
- Association of low-frequency and common variants, genes and regulatory regions with DKD
Methodological detailswhole-exome and whole-genome sequencing meta-analysis, case-control, WES and WGS meta-analysis, single-variant and gene-aggregate tests, replication in FinnGen genome-wide association study (GWAS)
- Whole-exome and whole-genome sequencing meta-analysis
- Case-control
- WES and WGS meta-analysis
- Single-variant and gene-aggregate tests
- Replication in FinnGen GWAS
Pooled result
As reported in the abstract
- THAP7 rs369250 (minor allele frequency (MAF)=49%), suggestive association, replicated in FinnGen GWAS for CKD and DKD phenotypes
- p=1.50 × 10-5
- Gene-aggregate meta-analysis: suggestive evidence at four genes; NAT16 (MAFPAV≤10%) and LTA (MAFPAV≤5%) replicated in FinnGen
- p<4.0 × 10-4
- Enhancer on chromosome 18q12.3 (MAFvariants≤5%), interacting with METTL4; lead variant replicated, predicted to alter MafB binding
- p=3.94 × 10-5
Further pooled results
LTA rs2229092 C allele and serum TNFR1, TNFR2, TNFR3
- Significantly lower TNFR1, TNFR2 and TNFR3 serum levels with the C allele in a subset of FinnDiane participants
Original publication
Whole-exome and whole-genome sequencing of 1064 individuals with type 1 diabetes reveals novel genes for diabetic kidney disease. Diabetologia. Published 6 August 2024. doi:10.
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