Molecular Epidemiology:
Center for Biomedical Research Excellence & Center for Molecular Epidemiology
COBRE Center for Molecular Epidemiology Phase III
Principal Investigator: Margaret Karagas, PhD
Funding: National Institute of General Medical Sciences (NIGMS) | NIH
Project Number: 5P30GM149408-02
Project Narrative: The primary goals of the center are to 1) evolve a state-of-the-art Biorepository and Biospecimen Resource Facility Core, 2) expand the pipeline of talented, diverse molecular epidemiologists, and provide the requisite mentorship, career development, and research resources to cultivate cutting-edge research and make investigators competitive for funding, and 3) enhance the governance structure, implementation approaches, stakeholder engagement, and evaluation to strengthen the center’s impact
Highlighted Publications
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Publication Link: Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens. This work demonstrates the potential of using breast milk as a noninvasive biomarker of breast cancer risk, improving our ability to detect early-stage disease and lowering the overall disease burden.
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Publication Link: The placenta is the organ that mediates transport of nutrients and waste materials between mother and fetus. Synchrotron X-ray fluorescence (SXRF) microanalysis is a tool for imaging the distribution and quantity of elements in biological tissue, which can be used to study metal transport across biological membranes. Our aims were to pilot placental biopsy specimen preparation techniques that could be integrated into an ongoing epidemiology birth cohort study without harming rates of sample acquisition.
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Publication Link: The intestinal microbiome plays a critical role in infant development, and delivery mode and feeding method (breast milk vs formula) are determinants of its composition. However, the importance of delivery mode beyond the first days of life is unknown, and studies of associations between infant feeding and microbiome composition have been generally limited to comparisons between exclusively breastfed and formula-fed infants, with little consideration given to combination feeding of both breast milk and formula.
We examined the associations of delivery mode and feeding method with infant intestinal microbiome composition at approximately 6 weeks of life. The infant intestinal microbiome at approximately 6 weeks of age is significantly associated with both delivery mode and feeding method, and the supplementation of breast milk feeding with formula is associated with a microbiome composition that resembles that of infants who are exclusively formula fed. These results may inform feeding choices and shed light on the mechanisms behind the lifelong health consequences of delivery and infant feeding modalities.
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Publication Link: Throughout their lifespans, humans continually interact with the microbial world, including those organisms which live in and on the human body. Research in this domain has revealed the extensive links between the human-associated microbiota and health. In particular, the microbiota of the human gut plays essential roles in digestion, nutrient metabolism, immune maturation and homeostasis, neurological signaling, and endocrine regulation. Microbial interaction networks are frequently estimated from data and are an indispensable tool for representing and understanding the conditional correlation between the microbes. In this high-dimensional setting, zero-inflation and unit-sum constraint for relative abundance data pose challenges to the reliable estimation of microbial interaction networks.
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Publication Link: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potential metabolic disruptors of concern for infants. Mothers participating in the New Hampshire Birth Cohort Study (NHBCS) provided a plasma sample during pregnancy to measure concentrations of seven PFAS, and infant weight and length were abstracted from well-child visits between birth and 12 months. Sex-specific growth patterns of child body mass index (BMI) were fit using a growth mixture model (GMM) and the relative risk ratios (RRR) and 95% Confidence Intervals (95% CI) for the association of maternal plasma PFAS with BMI growth patterns during infancy were estimated by using multinomial logistic model for the group probabilities in the GMM. Four growth patterns were identified: Group 1) a steep increase in BMI during the first 6 months, then a leveling off; Group 2) a gradual increase in BMI across the year; Group 3) a steep increase in BMI during months 1-3, then stable BMI; and Group 4) a gradual increase in BMI with plateau around 3 months (reference group). For boys, higher maternal pregnancy perfluorooctanoate concentrations were associated with a 60% decreased chance of being in group 3 as compared to group 4, after adjusting for potential confounding variables (RRR = 0.4; 95% CI: 0.1, 0.9). For girls, higher maternal perfluorooctane sulfonate (PFOS) concentrations during pregnancy were associated with a higher likelihood of following the growth pattern of groups 2 (RRR = 2.5; 95% CI: 1.0, 6.1) and 3 (RRR = 2.8; 95% CI: 1.0, 7.6) as compared to group 4, adjusting for potential confounding variables. In this cohort, sex-specific associations of maternal plasma PFAS concentrations during pregnancy with growth patterns during the first year of life were observed, with greater BMI growth observed among infant girls born to mothers with higher pregnancy concentrations of PFOS.
Prevalence and persistence of the ETV6/RUNX1
Principal Investigator: Margaret Karagas, PhD
Funding: National Institute of General Medical Sciences
Source of Support: University of Minnesota
Project Number: 5R01CA269393-02
Highlighted Publications
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Publication Link: Digital PCR (dPCR) can quantify cell-free viral DNA (DNAemia), a biomarker of active viral infection. To accelerate epidemiologic investigation into low-level viral reactivation in chronic disease, we have evaluated the performance of dPCR to detect cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia across platforms and blood matrices.
Project Narrative: This will include delivery of newborn dried blood spot (DBS) material from participants in the New Hampshire Birth Cohort Study (NHBCS) to the University of Minnesota (UMN) where RNA will be extracted to test for the presence of the ETV6/RUNX1 translocation. Dr. Karagas will be a key partner in the analysis and interpretation of results, and dissemination of study findings.