Identification of HKDC1 and BACE2 as Genes Influencing Glycemic Traits During Pregnancy Through Genome-Wide Association Studies.
Hayes MG, Urbanek M, Hivert MF, 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 Jr; for the HAPO Study Cooperative Research Group.
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.