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

M. Geoffrey Hayes*, Margrit Urbanek, Marie France Hivert, Loren L. Armstrong, Jean Morrison, Cong Guo, Lynn P. Lowe, Douglas A. Scheftner, Anna Pluzhnikov, David M. Levine, Caitlin P. McHugh, Christine M. Ackerman, Luigi Bouchard, Diane Brisson, Brian T. Layden, Daniel Mirel, Kimberly F. Doheny, Marysa V. Leya, Rachel N. Lown-Hecht, Alan R. DyerBoyd E. Metzger, Timothy E. Reddy, Nancy J. Cox, William L. Lowe

*Corresponding author for this work

Research output: Contribution to journalArticle

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3282-3291
Number of pages10
JournalDiabetes
Volume62
Issue number9
DOIs
StatePublished - Sep 1 2013

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Hayes, M. G., Urbanek, M., Hivert, M. F., Armstrong, L. L., Morrison, J., Guo, C., Lowe, L. P., Scheftner, D. A., Pluzhnikov, A., Levine, D. M., McHugh, C. P., Ackerman, C. M., Bouchard, L., Brisson, D., Layden, B. T., Mirel, D., Doheny, K. F., Leya, M. V., Lown-Hecht, R. N., ... Lowe, W. L. (2013). Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. Diabetes, 62(9), 3282-3291. https://doi.org/10.2337/db12-1692