title: Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.
abstract: 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.
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. ghayes@northwestern.edu
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
authors.forename: Margrit
authors.initials: M
authors.lastname: Urbanek
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hivert
authors.forename: Loren L
authors.initials: LL
authors.lastname: Armstrong
authors.forename: Jean
authors.initials: J
authors.lastname: Morrison
authors.forename: Cong
authors.initials: C
authors.lastname: Guo
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Lowe
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Scheftner
authors.forename: Anna
authors.initials: A
authors.lastname: Pluzhnikov
authors.forename: David M
authors.initials: DM
authors.lastname: Levine
authors.forename: Caitlin P
authors.initials: CP
authors.lastname: McHugh
authors.forename: Christine M
authors.initials: CM
authors.lastname: Ackerman
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
authors.forename: Diane
authors.initials: D
authors.lastname: Brisson
authors.forename: Brian T
authors.initials: BT
authors.lastname: Layden
authors.forename: Daniel
authors.initials: D
authors.lastname: Mirel
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Marysa V
authors.initials: MV
authors.lastname: Leya
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Lown-Hecht
authors.forename: Alan R
authors.initials: AR
authors.lastname: Dyer
authors.forename: Boyd E
authors.initials: BE
authors.lastname: Metzger
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Reddy
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: William L
authors.initials: WL
authors.lastname: Lowe
mesh_terms: D000293:Adolescent; D000328:Adult; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000502:physiology; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000502:physiology; D001786:Blood Glucose / Q000235:genetics*; D002096:C-Peptide / Q000097:blood; D005215:Fasting / Q000097:blood; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D011247:Pregnancy; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human
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