Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.

Journal Article (Journal Article)

Maternal metabolism during pregnancy impacts the developing fetus, affecting offspring birth weight and adiposity. This has important implications for metabolic health later in life (e.g., offspring of mothers with pre-existing or gestational diabetes mellitus have an increased risk of metabolic disorders in childhood). To identify genetic loci associated with measures of maternal metabolism obtained during an oral glucose tolerance test at ∼28 weeks' gestation, we performed a genome-wide association study of 4,437 pregnant mothers of European (n = 1,367), Thai (n = 1,178), Afro-Caribbean (n = 1,075), and Hispanic (n = 817) ancestry, along with replication of top signals in three additional European ancestry cohorts. In addition to identifying associations with genes previously implicated with measures of glucose metabolism in nonpregnant populations, we identified two novel genome-wide significant associations: 2-h plasma glucose and HKDC1, and fasting C-peptide and BACE2. These results suggest that the genetic architecture underlying glucose metabolism may differ, in part, in pregnancy.

Full Text

Duke Authors

Cited Authors

  • Hayes, MG; Urbanek, M; Hivert, M-F; Armstrong, LL; Morrison, J; Guo, C; Lowe, LP; Scheftner, DA; Pluzhnikov, A; Levine, DM; McHugh, CP; Ackerman, CM; Bouchard, L; Brisson, D; Layden, BT; Mirel, D; Doheny, KF; Leya, MV; Lown-Hecht, RN; Dyer, AR; Metzger, BE; Reddy, TE; Cox, NJ; Lowe, WL; HAPO Study Cooperative Research Group,

Published Date

  • September 2013

Published In

Volume / Issue

  • 62 / 9

Start / End Page

  • 3282 - 3291

PubMed ID

  • 23903356

Pubmed Central ID

  • PMC3749326

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

Digital Object Identifier (DOI)

  • 10.2337/db12-1692


  • eng

Conference Location

  • United States