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Article

Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies

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Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
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Department of Epidemiology, University of Colorado School of Public Health, Aurora, CO 80045, USA
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Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA
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Diabetes Unit, Massachusetts General Hospital, Boston, MA 02114, USA
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Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, CO 80045, USA
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Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Aurora, CO 80045, USA
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Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA
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Veterans Affairs Eastern Colorado Healthcare System, Aurora, CO 80045, USA
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Author to whom correspondence should be addressed.
Academic Editor: Pietro Vajro
Received: 20 April 2021 / Revised: 18 May 2021 / Accepted: 21 May 2021 / Published: 1 June 2021
To examine whether BMI-associated genetic risk variants modify the association of intrauterine diabetes exposure with childhood BMI z-scores, we assessed the interaction between 95 BMI-associated genetic variants and in utero exposure to maternal diabetes among 459 children in the Exploring Perinatal Outcomes among Children historical prospective cohort study (n = 86 exposed; 373 unexposed) in relation to age- and sex-standardized childhood BMI z-scores (mean age = 10.3 years, standard deviation = 1.5 years). For the genetic variants showing a nominally significant interaction, we assessed the relationship in an additional 621 children in Project Viva, which is an independent longitudinal cohort study, and used meta-analysis to combine the results for the two studies. Seven of the ninety-five genetic variants tested exhibited a nominally significant interaction with in utero exposure to maternal diabetes in relation to the offspring BMI z-score in EPOCH. Five of the seven variants exhibited a consistent direction of interaction effect across both EPOCH and Project Viva. While none achieved statistical significance in the meta-analysis after accounting for multiple testing, three variants exhibited a nominally significant interaction with in utero exposure to maternal diabetes in relation to offspring BMI z-score: rs10733682 near LMX1B (interaction β = 0.39; standard error (SE) = 0.17), rs17001654 near SCARB2 (β = 0.53; SE = 0.22), and rs16951275 near MAP2K5 (β = 0.37; SE = 0.17). BMI-associated genetic variants may enhance the association between exposure to in utero diabetes and higher childhood BMI, but larger studies of in utero exposures are necessary to confirm the observed nominally significant relationships. View Full-Text
Keywords: pediatric obesity; genetics; epidemiology; diabetes pediatric obesity; genetics; epidemiology; diabetes
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MDPI and ACS Style

Stanislawski, M.A.; Litkowski, E.; Fore, R.; Rifas-Shiman, S.L.; Oken, E.; Hivert, M.-F.; Lange, E.M.; Lange, L.A.; Dabelea, D.; Raghavan, S. Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies. Pediatr. Rep. 2021, 13, 279-288. https://0-doi-org.brum.beds.ac.uk/10.3390/pediatric13020036

AMA Style

Stanislawski MA, Litkowski E, Fore R, Rifas-Shiman SL, Oken E, Hivert M-F, Lange EM, Lange LA, Dabelea D, Raghavan S. Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies. Pediatric Reports. 2021; 13(2):279-288. https://0-doi-org.brum.beds.ac.uk/10.3390/pediatric13020036

Chicago/Turabian Style

Stanislawski, Maggie A., Elizabeth Litkowski, Ruby Fore, Sheryl L. Rifas-Shiman, Emily Oken, Marie-France Hivert, Ethan M. Lange, Leslie A. Lange, Dana Dabelea, and Sridharan Raghavan. 2021. "Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies" Pediatric Reports 13, no. 2: 279-288. https://0-doi-org.brum.beds.ac.uk/10.3390/pediatric13020036

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