Association of Genetic Predisposition and Physical Activity With Risk of Gestational Diabetes in Nulliparous Women

• Published in: JAMA network open 2022-08, Vol.5 (8), p.e2229158
• Main Authors: Pagel, Kymberleigh A, Chu, Hoyin, Ramola, Rashika, Guerrero, Rafael F, Chung, Judith H, Parry, Samuel, Reddy, Uma M, Silver, Robert M, Steller, Jonathan G, Yee, Lynn M, Wapner, Ronald J, Hahn, Matthew W, Natarajan, Sriraam, Haas, David M, Radivojac, Predrag
• Format: Article
• Language: English
• Subjects: Adult; Cohort Studies; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes, Gestational - epidemiology; Diabetes, Gestational - genetics; Exercise; Female; Genetic Predisposition to Disease; Genetics and Genomics; Gestational diabetes; Humans; Online Only; Original Investigation; Pregnancy
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2022.29158

Polygenic risk scores (PRS) for type 2 diabetes (T2D) can improve risk prediction for gestational diabetes (GD), yet the strength of the association between genetic and lifestyle risk factors has not been quantified. To assess the association of PRS and physical activity in existing GD risk models and identify patient subgroups who may receive the most benefits from a PRS or physical activity intervention. The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort was established to study individuals without previous pregnancy lasting at least 20 weeks (nulliparous) and to elucidate factors associated with adverse pregnancy outcomes. A subcohort of 3533 participants with European ancestry was used for risk assessment and performance evaluation. Participants were enrolled from October 5, 2010, to December 3, 2013, and underwent genotyping between February 19, 2019, and February 28, 2020. Data were analyzed from September 15, 2020, to November 10, 2021. Self-reported total physical activity in early pregnancy was quantified as metabolic equivalents of task (METs). Polygenic risk scores were calculated for T2D using contributions of 84 single nucleotide variants, weighted by their association in the Diabetes Genetics Replication and Meta-analysis Consortium data. Estimation of the development of GD from clinical, genetic, and environmental variables collected in early pregnancy, assessed using measures of model discrimination. Odds ratios and positive likelihood ratios were used to evaluate the association of PRS and physical activity with GD risk. A total of 3533 women were included in this analysis (mean [SD] age, 28.6 [4.9] years). In high-risk population subgroups (body mass index ≥25 or aged ≥35 years), individuals with high PRS (top 25th percentile) or low activity levels (METs