Genetic determinants of glycated hemoglobin in type 1 diabetes

DCCT/EDIC Research Group, Per-Henrik Groop, FinnDiane Study Group

Research output: Contribution to journalArticle

Abstract

Glycated hemoglobin (HbA 1c ) is an important measure of glycemia in diabetes. HbA 1c is influenced by environmental and genetic factors both in people with and in people without diabetes. We performed a genome-wide association study (GWAS) for HbA 1c in a Finnish type 1 diabetes (T1D) cohort, FinnDiane. Top results were examined for replication in T1D cohorts DCCT/EDIC, WESDR, CACTI, EDC, and RASS, and a meta-analysis was performed. Three SNPs in high linkage disequilibrium on chromosome 13 near relaxin family peptide receptor 2 (RXFP2) were associated with HbA 1c in FinnDiane at genome-wide significance (P < 5 3 10 28 ). The minor alleles of rs2085277 and rs1360072 were associated with higher HbA 1c also in the meta-analysis with RASS (P < 5 3 10 28 ), where these variants had minor allele frequencies ‡1%. Furthermore, these SNPs were associated with HbA 1c in an East Asian population without diabetes (P £ 0.013). A weighted genetic risk score created from 55 HbA 1c -associated variants from the literature was associated with HbA 1c in FinnDiane but explained only a small amount of variation. Understanding the genetic basis of glycemic control and HbA 1c may lead to better prevention of diabetes complications.

Original languageEnglish (US)
Pages (from-to)858-867
Number of pages10
JournalDiabetes
Volume68
Issue number4
DOIs
StatePublished - Apr 1 2019

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Glycosylated Hemoglobin A
Type 1 Diabetes Mellitus
Single Nucleotide Polymorphism
Meta-Analysis
Relaxin
Chromosomes, Human, Pair 13
Peptide Receptors
Genome-Wide Association Study
Linkage Disequilibrium
Diabetes Complications
Gene Frequency
Alleles
Genome
Population

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DCCT/EDIC Research Group, Per-Henrik Groop, & FinnDiane Study Group (2019). Genetic determinants of glycated hemoglobin in type 1 diabetes. Diabetes, 68(4), 858-867. https://doi.org/10.2337/db18-0573

Genetic determinants of glycated hemoglobin in type 1 diabetes. / DCCT/EDIC Research Group; Per-Henrik Groop; FinnDiane Study Group.

In: Diabetes, Vol. 68, No. 4, 01.04.2019, p. 858-867.

Research output: Contribution to journalArticle

DCCT/EDIC Research Group, Per-Henrik Groop & FinnDiane Study Group 2019, 'Genetic determinants of glycated hemoglobin in type 1 diabetes' Diabetes, vol. 68, no. 4, pp. 858-867. https://doi.org/10.2337/db18-0573
DCCT/EDIC Research Group, Per-Henrik Groop, FinnDiane Study Group. Genetic determinants of glycated hemoglobin in type 1 diabetes. Diabetes. 2019 Apr 1;68(4):858-867. https://doi.org/10.2337/db18-0573
DCCT/EDIC Research Group ; Per-Henrik Groop ; FinnDiane Study Group. / Genetic determinants of glycated hemoglobin in type 1 diabetes. In: Diabetes. 2019 ; Vol. 68, No. 4. pp. 858-867.
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