TY - JOUR
T1 - Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies
AU - Hayes, M. Geoffrey
AU - Urbanek, Margrit
AU - Hivert, Marie France
AU - Armstrong, Loren L.
AU - Morrison, Jean
AU - Guo, Cong
AU - Lowe, Lynn P.
AU - Scheftner, Douglas A.
AU - Pluzhnikov, Anna
AU - Levine, David M.
AU - McHugh, Caitlin P.
AU - Ackerman, Christine M.
AU - Bouchard, Luigi
AU - Brisson, Diane
AU - Layden, Brian T.
AU - Mirel, Daniel
AU - Doheny, Kimberly F.
AU - Leya, Marysa V.
AU - Lown-Hecht, Rachel N.
AU - Dyer, Alan R.
AU - Metzger, Boyd E.
AU - Reddy, Timothy E.
AU - Cox, Nancy J.
AU - Lowe, William L.
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
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U2 - 10.2337/db12-1692
DO - 10.2337/db12-1692
M3 - Article
C2 - 23903356
AN - SCOPUS:84887369859
SN - 0012-1797
VL - 62
SP - 3282
EP - 3291
JO - Diabetes
JF - Diabetes
IS - 9
ER -