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 Liu; James L Mills; Allan Vaag; Sjurdur F Olsen; Frank B Hu; Cuilin Zhang

doi:10.1136/bmjdrc-2019-000850

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

BMJ Open Diabetes Res Care. 2020 Jan;8(1):e000850. doi: 10.1136/bmjdrc-2019-000850.

Authors

Mengying Li^#¹, Mohammad L Rahman^#^{1

2}, Jing Wu³, Ming Ding⁴, Jorge E Chavarro^{4

5}, Yuan Lin⁶, Sylvia H Ley^{4

7}, Wei Bao⁸, Louise G Grunnet⁹, Stefanie N Hinkle¹, Anne Cathrine B Thuesen^{10

11}, Edwina Yeung¹, Robert E Gore-Langton¹², Seth Sherman¹², Line Hjort^{9

13}, Freja Bach Kampmann^{9

14}, Anne Ahrendt Bjerregaard¹⁵, Peter Damm^{13

16}, Fasil Tekola-Ayele¹, Aiyi Liu¹, James L Mills¹, Allan Vaag¹⁷, Sjurdur F Olsen¹⁵, Frank B Hu^{4

5}, Cuilin Zhang¹⁸

Affiliations

¹ Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
² Department of Population Medicine and Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, Massachusetts, USA.
³ Glotech, Rockville, Maryland, USA.
⁴ Department of Nutrition, Harvard University T.H. Chan School of Public Health, Boston, Massachusetts, USA.
⁵ Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁶ Epidemiology Department, Richard M. Fairbanks School of Public Health, Indiana University, Bloomington, Indiana, USA.
⁷ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
⁸ Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
⁹ Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
¹⁰ Steno Diabetes Center Copenhagen, Gentofte, Denmark.
¹¹ Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
¹² The Emmes Company, LLC, Rockville, Maryland, USA.
¹³ Departments of Obstetrics, Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark.
¹⁴ Division for Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Lyngby, Denmark.
¹⁵ Nutrition Group, Statens Serum Institut, Copenhagen, Denmark.
¹⁶ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹⁷ Early Clinical Development and Innovative Medicines, AstraZeneca, Mölndal, Sweden.
¹⁸ Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA zhangcu@mail.nih.gov.

^# Contributed equally.

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.

Keywords: dietary quality; genetic risk score; gestational diabetes; prospective cohort studies; type 2 diabetes.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Diabetes Mellitus, Type 2* / epidemiology
Diabetes Mellitus, Type 2* / genetics
Diabetes, Gestational* / epidemiology
Diabetes, Gestational* / genetics
Female
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide
Pregnancy

Abstract

Publication types

MeSH terms

Grants and funding