Genetic factors and risk of type 2 diabetes among women with a history of gestational diabetes: Findings from two independent populations

Mengying Li, Mohammad L. Rahman, Jing Wu, Ming DIng, Jorge E. Chavarro, Yuan Lin, Sylvia H. Ley, Wei Bao, Louise G. Grunnet, Stefanie N. Hinkle, Anne Cathrine B. Thuesen, Edwina Yeung, Robert E. Gore-Langton, Seth Sherman, Line Hjort, Freja Bach Kampmann, Anne Ahrendt Bjerregaard, Peter Damm, Fasil Tekola-Ayele, Aiyi LiuJames L. Mills, Allan Vaag, Sjurdur F. Olsen, Frank B. Hu, Cuilin Zhang

Research output: Contribution to journalArticle

Abstract

Objective Women with a history of gestational diabetes mellitus (GDM) have an exceptionally high risk for type 2 diabetes (T2D). Yet, little is known about genetic determinants for T2D in this population. We examined the association of a genetic risk score (GRS) with risk of T2D in two independent populations of women with a history of GDM and how this association might be modified by non-genetic determinants for T2D. Research design and methods This cohort study included 2434 white women with a history of GDM from the Nurses' Health Study II (NHSII, n=1884) and the Danish National Birth Cohort (DNBC, n=550). A GRS for T2D was calculated using 59 candidate single nucleotide polymorphisms for T2D identified from genome-wide association studies in European populations. An alternate healthy eating index (AHEI) score was derived to reflect dietary quality after the pregnancy affected by GDM. Results Women on average were followed for 21 years in NHSII and 13 years in DNBC, during which 446 (23.7%) and 155 (28.2%) developed T2D, respectively. The GRS was generally positively associated with T2D risk in both cohorts. In the pooled analysis, the relative risks (RRs) for increasing quartiles of GRS were 1.00, 0.97, 1.25 and 1.19 (p trend=0.02). In both cohorts, the association appeared to be stronger among women with poorer (AHEI <median) than better dietary quality (AHEI ≥median), although the interaction was not significant. For example, in NHSII, the RRs across increasing quartiles of GRS were 1.00, 0.99, 1.51 and 1.29 (p trend=0.06) among women with poorer dietary quality and 1.00, 0.83, 0.81 and 0.94 (p trend=0.79) among women with better dietary quality (p interaction=0.11). Conclusions Among white women with a history of GDM, higher GRS for T2D was associated with an increased risk of T2D.

Original languageEnglish (US)
Article numbere000850
JournalBMJ Open Diabetes Research and Care
Volume8
Issue number1
DOIs
StatePublished - Feb 13 2020

Keywords

  • dietary quality
  • genetic risk score
  • gestational diabetes
  • prospective cohort studies
  • type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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    Li, M., Rahman, M. L., Wu, J., DIng, M., Chavarro, J. E., Lin, Y., Ley, S. H., Bao, W., Grunnet, L. G., Hinkle, S. N., Thuesen, A. C. B., Yeung, E., Gore-Langton, R. E., Sherman, S., Hjort, L., Kampmann, F. B., Bjerregaard, A. A., Damm, P., Tekola-Ayele, F., ... Zhang, C. (2020). Genetic factors and risk of type 2 diabetes among women with a history of gestational diabetes: Findings from two independent populations. BMJ Open Diabetes Research and Care, 8(1), [e000850]. https://doi.org/10.1136/bmjdrc-2019-000850