Louis J Muglia

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

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Publications (187)1197.82 Total impact

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    ABSTRACT: Transposable elements (TEs) comprise approximately half of the human genome, and several independent lines of investigation have demonstrated their role in rewiring gene expression during development, evolution, and oncogenesis. The identification of their regulatory effects has largely been idiosyncratic, by linking activity with isolated genes. Their distribution throughout the genome raises critical questions - do these elements contribute to broad tissue-and lineage-specific regulation? If so, in what manner, as enhancers, promoters, RNAs? Here, we devise a novel approach to systematically dissect the genome-wide consequences of TE insertion on gene expression, and test the hypothesis that classes of endogenous retrovirus long terminal repeats (LTRs) exert tissue-specific regulation of adjacent genes. Using correlation of expression patterns across 18 tissue types, we reveal the tissue-specific uncoupling of gene expression due to 62 different LTR classes. These patterns are specific to the retroviral insertion, as the same genes in species without the LTRs do not exhibit the same effect. While the LTRs can be transcribed themselves, the most highly transcribed TEs do not have the largest effects on adjacent regulation of coding genes, suggesting they function predominantly as enhancers. Moreover, the tissue-specific patterns of gene expression that are detected by our method arise from a limited number of genes, rather than as a general consequence of LTR integration. These findings identify basic principles of co-opting LTRs for genome evolution, and support the utility of our method for the analysis of TE, or other specific gene sets, in relation to the rest of the genome. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Genome Biology and Evolution 03/2015; 7(4). DOI:10.1093/gbe/evv049 · 4.53 Impact Factor
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    ABSTRACT: OBJECTIVE: To test the hypothesis that exposure to fine particulate air pollution (PM2.5) is associated with stillbirth. STUDY DESIGN: Geo-spatial population-based cohort study using Ohio birth records (2006-2010) and local measures of PM2.5, recorded by the EPA (2005-2010) via 57 monitoring stations across Ohio. Geographic coordinates of the mother's residence for each birth were linked to the nearest PM2.5 monitoring station and monthly exposure averages calculated. The association between stillbirth and increased PM2.5 levels was estimated, with adjustment for maternal age, race, education level, quantity of prenatal care, smoking, and season of conception. RESULTS: There were 349,188 live births and 1,848 stillbirths of non-anomalous singletons (20-42 weeks) with residence </=10 km of a monitor station in Ohio during the study period. The mean PM2.5 level in Ohio was 13.3 mug/m3 [+/-1.8 SD, IQR(Q1: 12.1, Q3: 14.4, IQR: 2.3)], higher than the current EPA standard of 12 mug/m3. High average PM2.5 exposure through pregnancy was not associated with a significant increase in stillbirth risk, adjOR 1.21(95% CI 0.96,1.53), nor was it increased with high exposure in the 1st or 2nd trimester. However, exposure to high levels of PM2.5 in the third trimester of pregnancy was associated with 42% increased stillbirth risk, adjOR 1.42(1.06,1.91). CONCLUSIONS: Exposure to high levels of fine particulate air pollution in the third trimester of pregnancy is associated with increased stillbirth risk. Although the risk increase associated with high PM2.5 levels is modest, the potential impact on overall stillbirth rates could be robust as all pregnant women are potentially at risk.
    PLoS ONE 01/2015; 10(3):e0120594. DOI:10.1371/journal.pone.0120594 · 3.53 Impact Factor
  • James M. Greenberg, Louis J. Muglia
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    ABSTRACT: To assess the influence of birth spacing on neonatal morbidity, stratified by gestational age at birth.Study DesignPopulation-based retrospective cohort study using Ohio birth records, 2006-2011. We compared various interpregnancy interval (IPI) lengths in multiparous mothers with the rate and risk of adverse newborn outcomes. The frequency of neonatal intensive care unit (NICU) admission or neonatal transport to a tertiary care facility was calculated for births occurring after IPI lengths: <6, 6 to <12, 12 to <24, 24 to <60 and ≥60 months, and stratified by week of gestational age. Neonatal morbidity risk was calculated for each IPI compared to 12 to <24 months (referent), and adjusted for the concomitant influences gestational age at birth, maternal race, age and prior preterm birth.ResultsWe analyzed 395,146 birth outcomes of singleton non-anomalous neonates born to multiparous mothers. The frequency and adjusted odds of neonatal morbidity were lowest following IPI of 12 to <24 months (4.1%) compared to short IPIs of <6 months (5.7%, adjOR 1.40, 95% CI 1.32,1.49), 6 to <12 months (4.7%, adjOR 1.19, CI 1.13-1.25), and long IPIs 24 to <60 months (4.6%, adjOR 1.12, CI 1.08-1.17) and ≥60 months (5.8%, adjOR 1.34, CI 1.28-1.40), despite adjustment for important confounding factors including gestational age at birth. The lowest frequency of adverse neonatal outcomes occurred at 40-41 weeks for all IPI groups.The frequency of other individual immediate newborn morbidities were also increased following short and long IPIs compared to birth following a 12 to <24 month IPI.Conclusions Interpregnancy interval length is a significant contributor to neonatal morbidity, independent of gestational age at birth. Counseling women to plan an optimal amount of time between pregnancies is important for newborn health.
    American Journal of Obstetrics and Gynecology 11/2014; DOI:10.1016/j.ajog.2014.11.017 · 3.97 Impact Factor
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    ABSTRACT: Preterm birth is a leading cause of infant morbidity and mortality worldwide, but current interventions to prevent prematurity are largely ineffective. Preterm birth is increasingly recognized as an outcome that can result from a variety of pathological processes. Despite current research efforts, the mechanisms underlying these processes remain poorly understood and are influenced by a range of biological and environmental factors. Research with modern techniques is needed to understand the mechanisms responsible for preterm labor and birth and identify targets for diagnostic and therapeutic solutions. This review evaluates the state of reproductive science relevant to understanding the causes of preterm birth, identifies potential targets for prevention, and outlines challenges and opportunities for translating research findings into effective interventions.
    Science translational medicine 11/2014; 6(262):262sr5. DOI:10.1126/scitranslmed.3009871 · 14.41 Impact Factor
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    ABSTRACT: Negative feedback regulation of glucocorticoid (GC) synthesis and secretion occurs through the function of glucocorticoid receptor (GR) at sites in the hypothalamic–pituitary–adrenal (HPA) axis, as well as in brain regions such as the hippocampus, prefrontal cortex, and sympathetic nervous system. This function of GRs in negative feedback coordinates basal glucocorticoid secretion and stress-induced increases in secretion that integrate GC production with the magnitude and duration of the stressor. This review describes the effects of GR loss along major sites of negative feedback including the entire brain, the paraventricular nucleus of the hypothalamus (PVN), and the pituitary. In genetic mouse models, we evaluate circadian regulation of the HPA axis, stress-stimulated neuroendocrine response and behavioral activity, as well as the integrated response of organism metabolism. Our analysis provides information on contributions of region-specific GR-mediated negative feedback to provide insight in understanding HPA axis dysregulation and the pathogenesis of psychiatric and metabolic disorders.
    Frontiers in Neuroendocrinology 09/2014; 36. DOI:10.1016/j.yfrne.2014.09.002 · 7.58 Impact Factor
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    ABSTRACT: Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis.
    07/2014; 3(4). DOI:10.1016/j.molmet.2014.01.014
  • The Lancet 05/2014; 383(9929):1611-3. DOI:10.1016/S0140-6736(14)60583-3 · 39.21 Impact Factor
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    ABSTRACT: OBJECTIVE: Test the hypothesis that exposure to fine particles in the air (PM2.5) is associated with increased risk of preterm birth (PTB). STUDY DESIGN: Geo-spatial population-based cohort study using live birth records from Ohio(2007-2010) linked to average daily measures of PM2.5, recorded by 57 EPA network monitoring stations across the state. Geographic coordinates of the home residence for births were linked to the nearest monitoring station using ArcGIS. Association between PTB and high PM2.5 levels (above the EPA annual standard of 15ug/m3) was estimated using GEE, with adjustment for age, race, education, parity, insurance, tobacco, birth season and year, and baby gender. An exchangeable correlation matrix for the monitor stations was used in the models. Analyses limited to singleton births at 20-42 wks with no known chromosome abnormality occurring within 10km of a monitor station. RESULTS: The frequency of PTB was 8.5% and small for gestational age (SGA, BW < 2500 gm) was 6.9% in the study cohort, n= 224,921. High PM2.5 exposure > EPA recommended max occurred frequently during the study period, with 24,662 women (11%) having high exposure in all three trimesters. Pregnancies with high PM2.5 exposure through pregnancy had increased PTB risk even after adjustment for coexisting risk factors, aOR1.15(1.06-1.25). Assessed per trimester, high 3rd trimester PM2.5 had the highest PTB risk, aOR1.25(1.18-1.33). High exposure in 3rd trimester and through pregnancy also increased SGA risk, aOR1.16(1.09-1.24) and1.24(1.16-1.32) respectively. CONCLUSION: Exposure to high levels of fine particulate air pollution, PM2.5, in pregnancy is associated with increased risk of PTB and SGA. Although the risk increase associated with high PM2.5 levels is modest, the potential impact on overall PTB rates is robust as all pregnant women are potentially at risk. This may in part contribute to the higher preterm birth rates in Ohio compared to other states in the US, especially in urban areas.
    American Journal of Obstetrics and Gynecology 01/2014; 210(1):S346. DOI:10.1016/j.ajog.2013.10.736 · 3.97 Impact Factor
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    ABSTRACT: Administration of a single low dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been demonstrated to elicit long-lasting antidepressant effects in humans with depression, as well as in rodent models of depression. Although pharmacological studies have implicated the GluN2B subunit of the NMDA receptor in these effects, drugs targeting this subunit have off-target actions, and systemic administration of these compounds does not allow for delineation of specific brain regions involved. In this study, we assessed the role of GluN2B in the bed nucleus of the stria terminalis (BNST) in novelty-induced hypophagia (NIH) in mice. First, we verified that ketamine, as well as the GluN2B antagonist Ro25-6981, decreased the latency to consume food in a novel environment in a version of the NIH test. We then hypothesized that GluN2B-containing receptors within the BNST may be a target of systemic ketamine and contribute to behavioral effects. Through the combination of a GluN2B-floxed mouse line and stereotaxic delivery of lentiviral Cre recombinase, we found that targeted knockdown of this subunit within the BNST mimicked the reduction in affective behavior observed with systemic ketamine or Ro25-6981 in the NIH test. These data suggest a role for GluN2B-containing NMDARs within the BNST in the affective effects of systemic ketamine.
    Translational Psychiatry 12/2013; 3(12):e331. DOI:10.1038/tp.2013.103 · 4.36 Impact Factor
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    Louis J. Muglia, Dhavendra Kumar
    12/2013; 2. DOI:10.1016/j.atg.2013.10.003
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    ABSTRACT: It has recently been hypothesized that polygenic adaptation, resulting in modest allele frequency changes at many loci, could be a major mechanism behind the adaptation of complex phenotypes in human populations. Here we leverage the large number of variants that have been identified through genome-wide association (GWA) studies to comprehensively study signatures of natural selection on genetic variants associated with complex traits. Using population differentiation based methods, such as FST and phylogenetic branch length analyses, we systematically examined nearly 1300 SNPs associated with 38 complex phenotypes. Instead of detecting selection signatures at individual variants, we aimed to identify combined evidence of natural selection by aggregating signals across many trait associated SNPs. Our results have revealed some general features of polygenic selection on complex traits associated variants. First, natural selection acting on standing variants associated with complex traits is a common phenomenon. Second, characteristics of selection for different polygenic traits vary both temporarily and geographically. Third, some studied traits (e.g. height and urate level) could have been the primary targets of selection, as indicated by the significant correlation between the effect sizes and the estimated strength of selection in the trait associated variants; however, for most traits, the allele frequency changes in trait associated variants might have been driven by the selection on other correlated phenotypes. Fourth, the changes in allele frequencies as a result of selection can be highly stochastic, such that, polygenic adaptation may accelerate differentiation in allele frequencies among populations, but generally does not produce predictable directional changes. Fifth, multiple mechanisms (pleiotropy, hitchhiking, etc) may act together to govern the changes in allele frequencies of genetic variants associated with complex traits.
    12/2013; 2. DOI:10.1016/j.atg.2013.10.002
  • 12/2013; 1(6):e328-e330. DOI:10.1016/S2214-109X(13)70120-7
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    ABSTRACT: Preterm birth is a complex disorder defined by gestations of less than 37 weeks. While preterm birth is estimated to have a significant genetic component, relative few genes have been associated with preterm birth. Polymorphism in one such gene, follicle-stimulating hormone receptor (FSHR), has been associated with preterm birth in Finnish and African American mothers but not other populations. To refine the genetic association of FSHR with preterm birth we conducted a fine-mapping study at the FSHR locus in a Finnish cohort. We sequenced a total of 44 kb, including protein-coding and conserved non-coding regions, in 127 preterm and 135 term mothers. Overall, we identified 288 single nucleotide variants and 65 insertion/deletions of 1-2 bp across all subjects. While no common SNPs in protein-coding regions were associated with preterm birth, including one previously associated with timing of fertilization, multiple SNPs spanning the first and second intron showed the strongest associations. Analysis of the associated SNPs revealed that they form both a protective (OR = 0.50, 95% CI = 0.25-0.93) as well as a risk (OR = 1.89, 95% CI = 1.08-3.39) haplotype with independent effects. In these haplotypes, two SNPs, rs12052281 and rs72822025, were predicted to disrupt ZEB1 and ELF3 transcription factor binding sites, respectively. Our results show that multiple haplotypes at FSHR are associated with preterm birth and we discuss the frequency and structure of these haplotypes outside of the Finnish population as a potential explanation for the absence of FSHR associations in some populations.
    PLoS ONE 10/2013; 8(10):e78032. DOI:10.1371/journal.pone.0078032 · 3.53 Impact Factor
  • Gloria Laryea, Günther Schütz, Louis J Muglia
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    ABSTRACT: The glucocorticoid receptor (GR) regulates hypothalamic-pituitary-adrenal (HPA) axis activity during the stress response. The paraventricular nucleus (PVN) is a major site of negative feedback to coordinate the degree of the HPA axis activity with the magnitude of the exposed stressor. To define the function of endogenous PVN GR, we used Cre-loxP technology to disrupt different GR exons in Sim1-expressing neurons of the hypothalamus. GR exon 2 deleted mice (Sim1Cre-GRe2Δ) demonstrated 50% loss of PVN GR compared to an 80% GR loss in exon 3 deleted mice (Sim1Cre-GRe3Δ). Sim1Cre-GRe3Δ mice display stunted growth at birth but develop obesity in adulthood, and display impaired stress-induced glucose release. We observed elevated basal and stress-induced corticosterone levels in Sim1Cre-GRe3Δ mice, compared to control and Sim1Cre-GRe2Δ mice, and impaired dexamethasone suppression, indicating an inability to negatively regulate corticosterone secretion. Sim1Cre-GRe3Δ mice also showed increased corticotropin-releasing hormone mRNA in the PVN, increased basal plasma ACTH levels, and reduced locomotor behavior. We observed no differences in Sim1Cre-GRe2Δmice compared to control mice in any measure. Our behavioral data suggest that GR deletion in Sim1-expressing neurons has no effect on anxiety or despair-like behavior under basal conditions. We conclude that loss of PVN GR results in severe HPA axis hyperactivity and Cushing's syndrome-like phenotype, but does not affect anxiety and despair-like behaviors.
    Molecular Endocrinology 08/2013; 27(10). DOI:10.1210/me.2013-1187 · 4.20 Impact Factor
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    ABSTRACT: Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known. To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance. Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case--control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors. Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study.
    BMC Medical Genetics 07/2013; 14(1):77. DOI:10.1186/1471-2350-14-77 · 2.45 Impact Factor
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    ABSTRACT: Preterm birth (delivery at less than 37 weeks of gestation) is the leading cause of infant mortality worldwide. So far, the application of animal models to understand human birth timing has not substantially revealed mechanisms that could be used to prevent prematurity. However, with amassing data implicating an important role for genetics in the timing of the onset of human labor, the use of modern genomic approaches, such as genome-wide association studies, rare variant analyses using whole-exome or genome sequencing, and family-based designs, holds enormous potential. Although some progress has been made in the search for causative genes and variants associated with preterm birth, the major genetic determinants remain to be identified. Here, we review insights from and limitations of animal models for understanding the physiology of parturition, recent human genetic and genomic studies to identify genes involved in preterm birth, and emerging areas that are likely to be informative in future investigations. Further advances in understanding fundamental mechanisms, and the development of preventative measures, will depend upon the acquisition of greater numbers of carefully phenotyped pregnancies, large-scale informatics approaches combining genomic information with information on environmental exposures, and new conceptual models for studying the interaction between the maternal and fetal genomes to personalize therapies for mothers and infants. Information emerging from these advances will help us to identify new biomarkers for earlier detection of preterm labor, develop more effective therapeutic agents, and/or promote prophylactic measures even before conception.
    Genome Medicine 04/2013; 5(4):34. DOI:10.1186/gm438 · 4.94 Impact Factor
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    ABSTRACT: Our aim was to review the use of high-dimensional biology techniques, specifically transcriptomics, proteomics, and metabolomics, in amniotic fluid to elucidate the mechanisms behind preterm birth or assessment of fetal development. We performed a comprehensive MEDLINE literature search on the use of transcriptomic, proteomic, and metabolomic technologies for amniotic fluid analysis. All abstracts were reviewed for pertinence to preterm birth or fetal maturation in human subjects. Nineteen articles qualified for inclusion. Most articles described the discovery of biomarker candidates, but few larger, multicenter replication or validation studies have been done. We conclude that the use of high-dimensional systems biology techniques to analyze amniotic fluid has significant potential to elucidate the mechanisms of preterm birth and fetal maturation. However, further multicenter collaborative efforts are needed to replicate and validate candidate biomarkers before they can become useful tools for clinical practice. Ideally, amniotic fluid biomarkers should be translated to a noninvasive test performed in maternal serum or urine.
    Reproductive sciences (Thousand Oaks, Calif.) 04/2013; 21(1). DOI:10.1177/1933719113485292 · 2.18 Impact Factor
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    ABSTRACT: Our aim was to review the use of high-dimensional biology techniques, specifically transcriptomics, proteomics, and metabolomics, in amniotic fluid to elucidate the mechanisms behind preterm birth or assessment of fetal development. We performed a comprehensive MEDLINE literature search on the use of transcriptomic, proteomic, and metabolomic technologies for amniotic fluid analysis. All abstracts were reviewed for pertinence to preterm birth or fetal maturation in human subjects. Nineteen articles qualified for inclusion. Most articles described the discovery of biomarker candidates, but few larger, multicenter replication or validation studies have been done. We conclude that the use of high-dimensional systems biology techniques to analyze amniotic fluid has significant potential to elucidate the mechanisms of preterm birth and fetal maturation. However, further multicenter collaborative efforts are needed to replicate and validate candidate biomarkers before they can become useful tools for clinical practice. Ideally, amniotic fluid biomarkers should be translated to a noninvasive test performed in maternal serum or urine.
    Reproductive Sciences 04/2013; · 2.18 Impact Factor
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    ABSTRACT: Preterm birth (PTB) is a major global public health concern. However, little is known about the pathophysiology of spontaneous idiopathic PTB. We tested the hypothesis that rare variants in families would target specific genes and pathways that contribute to PTB risk in the general population. Whole-exome sequencing was performed on 10 PTB mothers from densely affected families including two mother-daughter pairs. We identified novel variants shared between the two mother-daughter pairs when compared to a 1000 Genomes Project background exome file and investigated these genes for pathway aggregation using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Genes in enriched pathways were then surveyed in the other six PTB exomes and tested for association in a larger number of nuclear families. The KEGG complement and coagulation cascade was one of the most enriched pathways in our two mother-daughter pairs. When the six genes found in this pathway (CFH, CR1, F13B, F5, CR2, and C4BPA) were examined for novel missense variants, half of all the exomes harbored at least one. Association analysis of variants in these six gene regions in nuclear families from Finland (237 cases and 328 controls) found statistically significant associations after multiple test corrections in three CR1 SNPs; the strongest in an exonic missense SNP, rs6691117, p value = 6.91e-5, OR = 1.71. Our results demonstrate the importance of the complement and coagulation cascades in the pathophysiology of PTB, and suggest potential screening and intervention approaches to prevent prematurity that target this pathway.
    Human Genetics 04/2013; 132(8). DOI:10.1007/s00439-013-1304-5 · 4.52 Impact Factor

Publication Stats

7k Citations
1,197.82 Total Impact Points

Institutions

  • 2012–2015
    • Cincinnati Children's Hospital Medical Center
      • • Department of Pediatrics
      • • Perinatal Institute
      Cincinnati, Ohio, United States
  • 2012–2014
    • University of Cincinnati
      • • College of Medicine
      • • Department of Pediatrics
      Cincinnati, Ohio, United States
  • 2013
    • University of Iowa
      • Department of Pediatrics
      Iowa City, Iowa, United States
  • 1999–2012
    • Washington University in St. Louis
      • • Department of Pediatrics
      • • Department of Obstetrics and Gynecology
      • • Department of Pathology and Immunology
      San Luis, Missouri, United States
  • 2010–2011
    • Vanderbilt University
      • Department of Pediatrics
      Nashville, MI, United States
  • 2007
    • Yale University
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      New Haven, Connecticut, United States
    • The University of Manchester
      Manchester, England, United Kingdom
    • Duke University
      Durham, North Carolina, United States
  • 2006
    • VU University Amsterdam
      • Department of Biological Psychology
      Amsterdamo, North Holland, Netherlands
  • 2002
    • University of Kentucky
      Lexington, Kentucky, United States
  • 2000
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States
  • 1995–2000
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1994–1999
    • Boston Children's Hospital
      • Division of Endocrinology
      Boston, MA, United States
  • 1997
    • Rady Children's Hospital
      San Diego, California, United States