Genetic Determinants of Glycated Hemoglobin in Type 1 Diabetes.

Glycated hemoglobin (HbA1c ) is an important measure of glycemia in diabetes. HbA1c is influenced by environmental and genetic factors, both in people with and without diabetes. We performed a genome-wide association study (GWAS) for HbA1c in a Finnish type 1 diabetes cohort, FinnDiane. Top results were examined for replication in type 1 diabetes cohorts DCCT/EDIC, WESDR, CACTI, EDC and RASS and a meta-analysis was performed. Three SNPs in high LD on chromosome 13 near relaxin family peptide receptor 2 ( RXFP2 ) were associated with HbA1c in FinnDiane at genome-wide significance (P <5×10-8 ). The minor alleles of rs2085277 and rs1360072 were associated with higher HbA1c also in the meta-analysis with RASS (P <5×10-8 ), where these variants had minor allele frequencies ≥1%. Furthermore, these SNPs were associated with HbA1c in a non-diabetic East Asian population ( P ≤0.013). A weighted genetic risk score created from 55 HbA1c associated variants from the literature was associated with HbA1c in FinnDiane but explained only a small amount of variation. Understanding the genetic basis of glycemic control and HbA1c may lead to better prevention of diabetic complications.