Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies
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 Perinata...
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doaj-b7d9d4d201d74ee1a40702b5ee8685142021-06-30T23:00:20ZengMDPI AGPediatric Reports2036-75032021-06-01133627928810.3390/pediatric13020036Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva StudiesMaggie A. Stanislawski0Elizabeth Litkowski1Ruby Fore2Sheryl L. Rifas-Shiman3Emily Oken4Marie-France Hivert5Ethan M. Lange6Leslie A. Lange7Dana Dabelea8Sridharan Raghavan9Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USADivision of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA 02215, USADepartment of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA 02215, USADepartment of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA 02215, USADepartment of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA 02215, USADivision of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USADivision of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USADepartment of Epidemiology, University of Colorado School of Public Health, Aurora, CO 80045, USADivision of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USATo 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 <i>LMX1B</i> (interaction β = 0.39; standard error (SE) = 0.17), rs17001654 near <i>SCARB2</i> (β = 0.53; SE = 0.22), and rs16951275 near <i>MAP2K5</i> (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.https://www.mdpi.com/2036-7503/13/2/36pediatric obesitygeneticsepidemiologydiabetes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maggie A. Stanislawski Elizabeth Litkowski Ruby Fore Sheryl L. Rifas-Shiman Emily Oken Marie-France Hivert Ethan M. Lange Leslie A. Lange Dana Dabelea Sridharan Raghavan |
spellingShingle |
Maggie A. Stanislawski Elizabeth Litkowski Ruby Fore Sheryl L. Rifas-Shiman Emily Oken Marie-France Hivert Ethan M. Lange Leslie A. Lange Dana Dabelea Sridharan Raghavan Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies Pediatric Reports pediatric obesity genetics epidemiology diabetes |
author_facet |
Maggie A. Stanislawski Elizabeth Litkowski Ruby Fore Sheryl L. Rifas-Shiman Emily Oken Marie-France Hivert Ethan M. Lange Leslie A. Lange Dana Dabelea Sridharan Raghavan |
author_sort |
Maggie A. Stanislawski |
title |
Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies |
title_short |
Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies |
title_full |
Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies |
title_fullStr |
Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies |
title_full_unstemmed |
Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies |
title_sort |
genetic interactions with intrauterine diabetes exposure in relation to obesity: the epoch and project viva studies |
publisher |
MDPI AG |
series |
Pediatric Reports |
issn |
2036-7503 |
publishDate |
2021-06-01 |
description |
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 <i>LMX1B</i> (interaction β = 0.39; standard error (SE) = 0.17), rs17001654 near <i>SCARB2</i> (β = 0.53; SE = 0.22), and rs16951275 near <i>MAP2K5</i> (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. |
topic |
pediatric obesity genetics epidemiology diabetes |
url |
https://www.mdpi.com/2036-7503/13/2/36 |
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