Genetic Determinants of Glycated Hemoglobin in Type 1 Diabetes

Publication Description
Glycated hemoglobin (HbA ) is an important measure of glycemia in diabetes. HbA 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 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 ( ) were associated with HbA in FinnDiane at genome-wide significance < 5 × 10 ). The minor alleles of rs2085277 and rs1360072 were associated with higher HbA also in the meta-analysis with RASS < 5 × 10 ), where these variants had minor allele frequencies ≥1%. Furthermore, these SNPs were associated with HbA in an East Asian population without diabetes ( ≤ 0.013). A weighted genetic risk score created from 55 HbA -associated variants from the literature was associated with HbA in FinnDiane but explained only a small amount of variation. Understanding the genetic basis of glycemic control and HbA may lead to better prevention of diabetes complications.

Primary Author
Syreeni,Anna
Sandholm,Niina
Cao,Jingjing
Toppila,Iiro
Maahs,David M.
Rewers,Marian J.
Snell-Bergeon,Janet
Costacou,Tina
Orchard,Trevor J.
Caramori,M. L.
Mauer,Michael
Klein,Barbara E. K.
Klein,Ronald
Valo,Erkka
Parkkonen,Maija
Forsblom,Carol
Harjutsalo,Valma
Paterson,Andrew D.
Groop,Per-Henrik

Volume
68

Issue
4

Start Page
858

Other Pages
867

Publisher
American Diabetes Association

URL
https://www.ncbi.nlm.nih.gov/pubmed/30674623 https://www.ncbi.nlm.nih.gov/pubmed/30674623



Reference Type
Journal Article

Periodical Full
Diabetes (New York, N.Y.)

Publication Year
2019

Publication Date
Apr

Place of Publication
United States

ISSN/ISBN
0012-1797

Document Object Index
10.2337/db18-0573