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2. Metabolomic data presents challenges for epidemiological meta-analysis: a case study of childhood body mass index from the ECHO consortium

Author

Prince, Nicole, Liang, Donghai, Tan, Youran, Alshawabkeh, Akram, Angel, Elizabeth Esther, Busgang, Stefanie A, Chu, Su H, Cordero, José F, Curtin, Paul, Dunlop, Anne L, Gilbert-Diamond, Diane, Giulivi, Cecilia, Hoen, Anne G, Karagas, Margaret R, Kirchner, David, Litonjua, Augusto A, Manjourides, Justin, McRitchie, Susan, Meeker, John D, Pathmasiri, Wimal, Perng, Wei, Schmidt, Rebecca J, Watkins, Deborah J, Weiss, Scott T, Zens, Michael S, Zhu, Yeyi, Lasky-Su, Jessica A, and Kelly, Rachel S

Subjects
Medical Biochemistry and Metabolomics, Reproductive Medicine, Biomedical and Clinical Sciences, Women's Health, Clinical Research, Pediatric, Reproductive health and childbirth, Child, Female, Pregnancy, Humans, Child, Preschool, Body Mass Index, Reproducibility of Results, Metabolomics, Linear Models, Lysine, Metabolomic meta-analysis, Metabolomic epidemiology, Maternal metabolites, Childhood obesity, Analytical Chemistry, Biochemistry and Cell Biology, Clinical Sciences, Biochemistry and cell biology, Medical biochemistry and metabolomics, Analytical chemistry
Abstract

IntroductionMeta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility.ObjectiveThe objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework.MethodsWe used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure.ResultsOnly 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P  100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology.

Published
2024

5. Greater Gestational Vitamin D Status is Associated with Reduced Childhood Behavioral Problems in the Environmental Influences on Child Health Outcomes Program

Author

Melough, Melissa M, Li, Mingyi, Hamra, Ghassan, Palmore, Meredith, Sauder, Katherine A, Dunlop, Anne L, LeWinn, Kaja Z, Zhao, Qi, Kelly, Rachel S, Switkowski, Karen M, Hipwell, Alison E, Korrick, Susan A, Collett, Brent R, MacKenzie, Debra, Nozadi, Sara S, Kerver, Jean M, Schmidt, Rebecca J, McGrath, Monica, Sathyanarayana, Sheela, and Outcomes, program collaborators for Environmental influences on Child Health

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Complementary and Integrative Health, Nutrition, Clinical Research, Behavioral and Social Science, Neurosciences, Pediatric, Prevention, Prevention of disease and conditions, and promotion of well-being, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Reproductive health and childbirth, Good Health and Well Being, Child, Pregnancy, Humans, Female, Child, Preschool, Vitamin D, Problem Behavior, Vitamin D Deficiency, Child Development, Outcome Assessment, Health Care, program collaborators for Environmental influences on Child Health Outcomes, 25-hydroxyvitamin D, behavioral problems, externalizing behaviors, internalizing behaviors, pregnancy, prenatal nutrition, vitamin D, Animal Production, Food Sciences, Nutrition & Dietetics, Animal production, Food sciences, Nutrition and dietetics
Abstract

BackgroundVitamin D deficiency is common in pregnancy. Vitamin D plays an important role in the developing brain, and deficiency may impair childhood behavioral development.ObjectivesThis study examined the relationship between gestational 25(OH)D concentrations and childhood behavior in the Environmental influences on Child Health Outcomes (ECHO) Program.MethodsMother-child dyads from ECHO cohorts with data available on prenatal (first trimester through delivery) or cord blood 25(OH)D and childhood behavioral outcomes were included. Behavior was assessed using the Strengths and Difficulties Questionnaire or the Child Behavior Checklist, and data were harmonized using a crosswalk conversion. Linear mixed-effects models examined associations of 25(OH)D with total, internalizing, and externalizing problem scores while adjusting for important confounders, including age, sex, and socioeconomic and lifestyle factors. The effect modification by maternal race was also assessed.ResultsEarly (1.5-5 y) and middle childhood (6-13 y) outcomes were examined in 1688 and 1480 dyads, respectively. Approximately 45% were vitamin D deficient [25(OH)D < 20 ng/mL], with Black women overrepresented in this group. In fully adjusted models, 25(OH)D concentrations in prenatal or cord blood were negatively associated with externalizing behavior T-scores in middle childhood [-0.73 (95% CI: -1.36, -0.10) per 10 ng/mL increase in gestational 25(OH)D]. We found no evidence of effect modification by race. In a sensitivity analysis restricted to those with 25(OH)D assessed in prenatal maternal samples, 25(OH)D was negatively associated with externalizing and total behavioral problems in early childhood.ConclusionsThis study confirmed a high prevalence of vitamin D deficiency in pregnancy, particularly among Black women, and revealed evidence of an association between lower gestational 25(OH)D and childhood behavioral problems. Associations were more apparent in analyses restricted to prenatal rather than cord blood samples. Interventions to correct vitamin D deficiency during pregnancy should be explored as a strategy to improve childhood behavioral outcomes.

Published
2023

6. Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations

Author

Feofanova, Elena V, Brown, Michael R, Alkis, Taryn, Manuel, Astrid M, Li, Xihao, Tahir, Usman A, Li, Zilin, Mendez, Kevin M, Kelly, Rachel S, Qi, Qibin, Chen, Han, Larson, Martin G, Lemaitre, Rozenn N, Morrison, Alanna C, Grieser, Charles, Wong, Kari E, Gersztern, Robert E, Zhao, Zhongming, Lasky-Su, Jessica, and Yu, Bing

Subjects
Genetics, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Good Health and Well Being, Humans, Quantitative Trait Loci, Ethnicity, Metabolome, Genome-Wide Association Study, Polymorphism, Single Nucleotide, NHLBI Trans-Omics for Precision Medicine
Abstract

Circulating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs and their biologically plausible genes. Among those novel replicated variant-metabolite pairs, follow-up analyses have revealed that 26 metabolites have colocalized with 21 tissues, seven metabolite-disease outcome associations have been putatively causal, and 7 metabolites might be regulated by plasma protein levels. Our results have depicted the genetic contribution to circulating metabolite levels, providing additional insights into understanding human disease.

Published
2023

7. Opportunities for understanding the COVID-19 pandemic and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) program

Author

Bekelman, Traci A, Trasande, Leonardo, Law, Andrew, Blackwell, Courtney K, Jacobson, Lisa P, Bastain, Theresa M, Breton, Carrie V, Elliott, Amy J, Ferrara, Assiamira, Karagas, Margaret R, Aschner, Judy L, Bornkamp, Nicole, Camargo, Carlos A, Comstock, Sarah S, Dunlop, Anne L, Ganiban, Jody M, Gern, James E, Karr, Catherine J, Kelly, Rachel S, Lyall, Kristen, O’Shea, T Michael, Schweitzer, Julie B, and LeWinn, Kaja Z

Subjects
Paediatrics, Biomedical and Clinical Sciences, Neurosciences, Prevention, Pediatric, Clinical Research, Health Services, American Indian or Alaska Native, Pediatric Research Initiative, 2.4 Surveillance and distribution, Aetiology, Good Health and Well Being, life course approach, environmental exposures, health disparities, parent-child dyads, pediatric health, health behaviors, Paediatrics and Reproductive Medicine, Other Medical and Health Sciences
Abstract

ObjectiveOngoing pediatric cohort studies offer opportunities to investigate the impact of the COVID-19 pandemic on children's health. With well-characterized data from tens of thousands of US children, the Environmental influences on Child Health Outcomes (ECHO) Program offers such an opportunity.MethodsECHO enrolled children and their caregivers from community- and clinic-based pediatric cohort studies. Extant data from each of the cohorts were pooled and harmonized. In 2019, cohorts began collecting data under a common protocol, and data collection is ongoing with a focus on early life environmental exposures and five child health domains: birth outcomes, neurodevelopment, obesity, respiratory, and positive health. In April of 2020, ECHO began collecting a questionnaire designed to assess COVID-19 infection and the pandemic's impact on families. We describe and summarize the characteristics of children who participated in the ECHO Program during the COVID-19 pandemic and novel opportunities for scientific advancement.ResultsThis sample (n = 13,725) was diverse by child age (31% early childhood, 41% middle childhood, and 16% adolescence up to age 21), sex (49% female), race (64% White, 15% Black, 3% Asian, 2% American Indian or Alaska Native,

Published
2023

9. Cardiometabolic Pregnancy Complications in Association With Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO

Author

Lyall, Kristen, Ning, Xuejuan, Aschner, Judy L, Avalos, Lyndsay A, Bennett, Deborah H, Bilder, Deborah A, Bush, Nicole R, Carroll, Kecia N, Chu, Su H, Croen, Lisa A, Dabelea, Dana, Daniels, Julie L, Duarte, Christiane, Elliott, Amy J, Fallin, M Daniele, Ferrara, Assiamira, Hertz-Picciotto, Irva, Hipwell, Alison E, Jensen, Elizabeth T, Johnson, Susan L, Joseph, Robert M, Karagas, Margaret, Kelly, Rachel S, Lester, Barry M, Margolis, Amy, McEvoy, Cindy T, Messinger, Daniel, Neiderhiser, Jenae M, O’Connor, Thomas G, Oken, Emily, Sathyanarayana, Sheela, Schmidt, Rebecca J, Sheinkopf, Stephen J, Talge, Nicole M, Turi, Kedir N, Wright, Rosalind J, Zhao, Qi, Newschaffer, Craig, Volk, Heather E, Ladd-Acosta, Christine, and Outcomes, on behalf of program collaborators for Environmental Influences on Child Health

Subjects
Epidemiology, Health Sciences, Perinatal Period - Conditions Originating in Perinatal Period, Mental Health, Autism, Contraception/Reproduction, Intellectual and Developmental Disabilities (IDD), Pediatric, Brain Disorders, Clinical Research, Prevention, Aetiology, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Metabolic and endocrine, Reproductive health and childbirth, Autism Spectrum Disorder, Autistic Disorder, Cardiovascular Diseases, Child, Diabetes, Gestational, Female, Humans, Infant, Newborn, Pregnancy, Premature Birth, autism, cardiometabolic complications, obesity, pregnancy complications, Social Responsiveness Scale, Mathematical Sciences, Medical and Health Sciences
Abstract

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (β = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (β = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.

Published
2022

10. Urinary eicosanoid levels in early life and risk of atopic disease in childhood

Author

Chen, Liang, Brustad, Nicklas, Kim, Min, Luo, Yang, Wang, Tingting, Ali, Mina, Prince, Nicole, Chen, Yulu, Chu, Su, Begum, Sofina, Mendez, Kevin, Kelly, Rachel S., Schoos, Ann-Marie, Rasmussen, Morten A., Zurita, Javier, Kolmert, Johan, Stokholm, Jakob, Litonjua, Augusto, Weiss, Scott T., Bønnelykke, Klaus, Wheelock, Craig E., Lasky-Su, Jessica, and Chawes, Bo

Published
2024
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11. Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma

Author

Mendez, Kevin M., Begum, Sofina, Tiwari, Anshul, Sharma, Rinku, Chen, Qingwen, Kelly, Rachel S., Prince, Nicole, Huang, Mengna, Kachroo, Priyadarshini, Chu, Su H., Chen, Yulu, Lee-Sarwar, Kathleen, Broadhurst, David I., Reinke, Stacey N., Gerszten, Robert, Clish, Clary, Avila, Lydiana, Celedón, Juan C., Wheelock, Craig E., Weiss, Scott T., McGeachie, Michael, and Lasky-Su, Jessica A.

Published
2024
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12. Pharmacometabolomics of Asthma as a Road Map to Precision Medicine

Author

Kelly, Rachel S., Cote, Margaret F., Begum, Sofina, Lasky-Su, Jessica, Michel, Martin C., Editor-in-Chief, Barrett, James E., Editorial Board Member, Centurión, David, Editorial Board Member, Flockerzi, Veit, Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Meier, Kathryn Elaine, Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, Ghini, Veronica, editor, Stringer, Kathleen A., editor, and Luchinat, Claudio, editor

Published
2023
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20. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Kachroo, Priyadarshini, Hecker, Julian, Chawes, Bo L, Ahluwalia, Tarunveer S, Cho, Michael H, Qiao, Dandi, Kelly, Rachel S, Chu, Su H, Virkud, Yamini V, Huang, Mengna, Barnes, Kathleen C, Burchard, Esteban G, Eng, Celeste, Hu, Donglei, Celedón, Juan C, Daya, Michelle, Levin, Albert M, Gui, Hongsheng, Williams, L Keoki, Forno, Erick, Mak, Angel CY, Avila, Lydiana, Soto-Quiros, Manuel E, Cloutier, Michelle M, Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A, Lange, Christoph, Weiss, Scott T, Lasky-Su, Jessica A, National Heart, Lung, Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Allred, Nicholette Palmer, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, and Das, Sayantan

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Research, Asthma, Genetics, Pediatric, Biotechnology, Human Genome, Lung, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Cell Adhesion Molecules, Child, Child, Preschool, Costa Rica, Female, Forced Expiratory Volume, Humans, Interferon Regulatory Factors, Male, Middle Aged, Respiratory Physiological Phenomena, Vital Capacity, Whole Genome Sequencing, Young Adult, airway hyperresponsiveness, asthma, lung function, whole genome sequencing, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

BackgroundAsthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma.MethodsWGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes.ResultsA genome-wide significant association was identified between baseline FEV1/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10-8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10-6). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV1 (P = 3.3 × 10-3), postbronchodilator (PB) FEV1 (7.3 × 10-3), and PB FEV1/FVC ratio (P = 2.7 × 10-3). The identified baseline FEV1/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR.ConclusionsThese findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

Published
2019

21. Prediagnostic plasma metabolomics and the risk of amyotrophic lateral sclerosis

Author

Bjornevik, Kjetil, Zhang, Zhongli, O'Reilly, Éilis J, Berry, James D, Clish, Clary B, Deik, Amy, Jeanfavre, Sarah, Kato, Ikuko, Kelly, Rachel S, Kolonel, Laurence N, Liang, Liming, Marchand, Loic Le, McCullough, Marjorie L, Paganoni, Sabrina, Pierce, Kerry A, Schwarzschild, Michael A, Shadyab, Aladdin H, Wactawski-Wende, Jean, Wang, Dong D, Wang, Ying, Manson, JoAnn E, and Ascherio, Alberto

Subjects
Neurodegenerative, Rare Diseases, Brain Disorders, Neurosciences, ALS, Clinical Research, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Amyotrophic Lateral Sclerosis, Case-Control Studies, Chromatography, Liquid, Female, Humans, Incidence, Male, Mass Spectrometry, Metabolome, Metabolomics, Middle Aged, Prospective Studies, Risk, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo identify prediagnostic plasma metabolomic biomarkers associated with amyotrophic lateral sclerosis (ALS).MethodsWe conducted a global metabolomic study using a nested case-control study design within 5 prospective cohorts and identified 275 individuals who developed ALS during follow-up. We profiled plasma metabolites using liquid chromatography-mass spectrometry and identified 404 known metabolites. We used conditional logistic regression to evaluate the associations between metabolites and ALS risk. Further, we used machine learning analyses to determine whether the prediagnostic metabolomic profile could discriminate ALS cases from controls.ResultsA total of 31 out of 404 identified metabolites were associated with ALS risk (p < 0.05). We observed inverse associations (n = 27) with plasma levels of diacylglycerides and triacylglycerides, urate, purine nucleosides, and some organic acids and derivatives, while we found positive associations for a cholesteryl ester, 2 phosphatidylcholines, and a sphingomyelin. The number of significant associations increased to 67 (63 inverse) in analyses restricted to cases with blood samples collected within 5 years of onset. None of these associations remained significant after multiple comparison adjustment. Further, we were not able to reliably distinguish individuals who became cases from controls based on their metabolomic profile using partial least squares discriminant analysis, elastic net regression, random forest, support vector machine, or weighted correlation network analyses.ConclusionsAlthough the metabolomic profile in blood samples collected years before ALS diagnosis did not reliably separate presymptomatic ALS cases from controls, our results suggest that ALS is preceded by a broad, but poorly defined, metabolic dysregulation years before the disease onset.

Published
2019

23. Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma

Author

Kachroo, Priyadarshini, Stewart, Isobel D., Kelly, Rachel S., Stav, Meryl, Mendez, Kevin, Dahlin, Amber, Soeteman, Djøra I., Chu, Su H., Huang, Mengna, Cote, Margaret, Knihtilä, Hanna M., Lee-Sarwar, Kathleen, McGeachie, Michael, Wang, Alberta, Wu, Ann Chen, Virkud, Yamini, Zhang, Pei, Wareham, Nicholas J., Karlson, Elizabeth W., Wheelock, Craig E., Clish, Clary, Weiss, Scott T., Langenberg, Claudia, and Lasky-Su, Jessica A.

Published
2022
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24. Immunomodulatory metabolites in IgE‐mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling.

Author

Virkud, Yamini V., Styles, Jennifer N., Kelly, Rachel S., Patil, Sarita U., Ruiter, Bert, Smith, Neal P., Clish, Clary, Wheelock, Craig E., Celedón, Juan C., Litonjua, Augusto A., Bunyavanich, Supinda, Weiss, Scott T., Baker, Erin S., Lasky‐Su, Jessica A., and Shreffler, Wayne G.

Abstract

Background: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE‐mediated food allergy are unknown. Objective: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT. Methods: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes. Results: Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10−20) and linoleic acid derivatives (q = 3.8 × 10−5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10−8), eicosanoids (q = 7.9 × 10−7), and histidine pathways (q =.015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p =.0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p =.01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p =.0015) were higher in SU. Conclusions: We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T‐cell subsets, suggesting potential mechanisms of tolerance in immunotherapy. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Neighborhood Food Access in Early Life and Trajectories of Child Body Mass Index and Obesity.

Author

Aris, Izzuddin M., Wu, Allison J., Lin, Pi-I D., Zhang, Mingyu, Farid, Huma, Hedderson, Monique M., Zhu, Yeyi, Ferrara, Assiamira, Chehab, Rana F., Barrett, Emily S., Carnell, Susan, Camargo Jr, Carlos A., Chu, Su H., Mirzakhani, Hooman, Kelly, Rachel S., Comstock, Sarah S., Strakovsky, Rita S., O'Connor, Thomas G., Ganiban, Jody M., and Dunlop, Anne L.

Published
2024
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26. Gestational diabetes mellitus, prenatal maternal depression, and risk for postpartum depression: an Environmental influences on Child Health Outcomes (ECHO) Study

Author

Shuffrey, Lauren C., Lucchini, Maristella, Morales, Santiago, Sania, Ayesha, Hockett, Christine, Barrett, Emily, Carroll, Kecia N., Cioffi, Camille C., Dabelea, Dana, Deoni, Sean, Dunlop, Anne L., Deutsch, Arielle, Fifer, William P., Firestein, Morgan R., Hedderson, Monique M., Jacobson, Melanie, Kelly, Rachel S., Kerver, Jean M., Mason, W. Alex, Mirzakhani, Hooman, O’Connor, Thomas G., Trasande, Leonardo, Weiss, Scott, Wright, Rosalind, Zhu, Yeyi, Crum, Rosa M., Lee, Seonjoo, Elliott, Amy J., and Monk, Catherine

Published
2022
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28. Biomarkers in Obstructive Airway Diseases

Author

Kelly, Rachel S., Stringer, Kathleen A., Wendt, Chris H., Rounds, Sharon I.S., Series Editor, Dixon, Anne, Series Editor, Schnapp, Lynn M., Series Editor, Gomez, Jose L., editor, Himes, Blanca E., editor, and Kaminski, Naftali, editor

Published
2020
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30. NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review

Author

Oldham, William M., Hemnes, Anna R., Aldred, Micheala A., Barnard, John, Brittain, Evan L., Chan, Stephen Y., Cheng, Feixiong, Cho, Michael H., Desai, Ankit A., Garcia, Joe G.N., Geraci, Mark W., Ghiassian, Susan D., Hall, Kathryn T., Horn, Evelyn M., Jain, Mohit, Kelly, Rachel S., Leopold, Jane A., Lindstrom, Sara, Modena, Brian D., Nichols, William C., Rhodes, Christopher J., Sun, Wei, Sweatt, Andrew J., Vanderpool, Rebecca R., Wilkins, Martin R., Wilmot, Beth, Zamanian, Roham T., Fessel, Joshua P., Aggarwal, Neil R., Loscalzo, Joseph, and Xiao, Lei

Published
2021
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31. Acylcarnitines are associated with lower depressive symptomatology in a mainland puerto rican cohort.

Author

Palacios, Natalia, Bhupathiraju, Shilpa N., Kelly, Rachel S., Lee, Jong Soo, Ordovas, Jose M., and Tucker, Katherine L.

Subjects
CENTER for Epidemiologic Studies Depression Scale, PUERTO Ricans, GENE regulatory networks, OLDER people, MULTIPLE comparisons (Statistics)
Abstract

Introduction: Recent studies have implicated acetyl-l-carnitine as well as other acylcarnitines in depression. To our knowledge, no untargeted metabolomics studies have been conducted among US mainland Puerto Ricans. Objectives: We conducted untargeted metabolomic profiling on plasma from 736 participants of the Boston Puerto Rican Health Study. Methods: Using Weighted Gene Co-expression Network Analysis, we identified metabolite modules associated with depressive symptomatology, assessed via the Center for Epidemiologic Studies Depression scale. We identified metabolites contributing to these modules and assessed the relationship between these metabolites and depressive symptomatology. Results: 621 annotated metabolites clustered into eight metabolite modules, of which one, the acylcarnitine module, was significantly inversely associated with depressive symptomatology (β = − 27.7 (95% CI (− 54.5—0.8); p = 0.043). Several metabolite hub features in the acylcarnitine module were significantly associated with depressive symptomatology, after correction for multiple comparisons. Conclusions: In this untargeted plasma metabolomics study among mainland Puerto Rican older adults, acylcarnitines, as a metabolite module were inversely associated with depressive symptomatology. [ABSTRACT FROM AUTHOR]

Published
2024
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35. An Unhealthy Dietary Pattern during Pregnancy is Associated with Neurodevelopmental Disorders in Childhood and Adolescence

Author

Horner, David, primary, Jepsen, Jens Richardt M., additional, Chawes, Bo, additional, Aagaard, Kristina, additional, Rosenberg, Julie B., additional, Mohammadzadeh, Parisa, additional, Sevelsted, Astrid, additional, Følsgaard, Nilo, additional, Vinding, Rebecca, additional, Fagerlund, Birgitte, additional, Pantelis, Christos, additional, Bilenberg, Niels, additional, Pedersen, Casper-Emil T., additional, Eliasen, Anders, additional, Chen, Yulu, additional, Prince, Nicole, additional, Chu, Su H., additional, Kelly, Rachel S., additional, Lasky-Su, Jessica, additional, Halldorsson, Thorhallur I., additional, Glenthøj, Birte Y., additional, Bønnelykke, Klaus, additional, Ebdrup, Bjørn H., additional, Stokholm, Jakob, additional, and Rasmussen, Morten Arendt, additional

Published
2024
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37. Mirnaome-Metabolome Wide Association Study Reveals Effects of Mirna Regulation in Eosinophilia and Airflow Obstruction in Childhood Asthma

Author

Sharma, Rinku, primary, Mendez, Kevin, additional, Begum, Sofina, additional, Chu, Su H., additional, Prince, Nicole, additional, Hecker, Julian, additional, Kelly, Rachel S., additional, Chen, Qingwen, additional, Wheelock, Craig E., additional, Celedón, Juan, additional, Clish, Clary, additional, Gertszen, Robert, additional, Tantisira, Kelan G., additional, Weiss, Scott T., additional, Lasky-Su, Jessica A., additional, and McGeachie, Michael, additional

Published
2024
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38. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Author

Machiela, Mitchell J, Lan, Qing, Slager, Susan L, Vermeulen, Roel CH, Teras, Lauren R, Camp, Nicola J, Cerhan, James R, Spinelli, John J, Wang, Sophia S, Nieters, Alexandra, Vijai, Joseph, Yeager, Meredith, Wang, Zhaoming, Ghesquières, Hervé, McKay, James, Conde, Lucia, de Bakker, Paul IW, Cox, David G, Burdett, Laurie, Monnereau, Alain, Flowers, Christopher R, De Roos, Anneclaire J, Brooks-Wilson, Angela R, Giles, Graham G, Melbye, Mads, Gu, Jian, Jackson, Rebecca D, Kane, Eleanor, Purdue, Mark P, Vajdic, Claire M, Albanes, Demetrius, Kelly, Rachel S, Zucca, Mariagrazia, Bertrand, Kimberly A, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Hutchinson, Amy, Zhi, Degui, Habermann, Thomas M, Link, Brian K, Novak, Anne J, Dogan, Ahmet, Asmann, Yan W, Liebow, Mark, Thompson, Carrie A, Ansell, Stephen M, Witzig, Thomas E, Tilly, Hervé, Haioun, Corinne, Molina, Thierry J, Hjalgrim, Henrik, Glimelius, Bengt, Adami, Hans-Olov, Roos, Göran, Bracci, Paige M, Riby, Jacques, Smith, Martyn T, Holly, Elizabeth A, Cozen, Wendy, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Tinker, Lesley F, North, Kari E, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, Lightfoot, Tracy, Crouch, Simon, Smith, Alex, Roman, Eve, Diver, W Ryan, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Villano, Danylo J, Zheng, Tongzhang, Zhang, Yawei, Holford, Theodore R, Turner, Jenny, Southey, Melissa C, Clavel, Jacqueline, Virtamo, Jarmo, Weinstein, Stephanie, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Boeing, Heiner, Tjønneland, Anne, Angelucci, Emanuele, Di Lollo, Simonetta, Rais, Marco, De Vivo, Immaculata, Giovannucci, Edward, Kraft, Peter, and Huang, Jinyan

Subjects
Clinical Research, Rare Diseases, Genetics, Cancer, Hematology, Lymphoma, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Lymphoma, B-Cell, Male, Middle Aged, Prospective Studies, Telomere, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

Published
2016

39. A genome-wide association study of marginal zone lymphoma shows association to the HLA region.

Author

Vijai, Joseph, Wang, Zhaoming, Berndt, Sonja I, Skibola, Christine F, Slager, Susan L, de Sanjose, Silvia, Melbye, Mads, Glimelius, Bengt, Bracci, Paige M, Conde, Lucia, Birmann, Brenda M, Wang, Sophia S, Brooks-Wilson, Angela R, Lan, Qing, de Bakker, Paul IW, Vermeulen, Roel CH, Portlock, Carol, Ansell, Stephen M, Link, Brian K, Riby, Jacques, North, Kari E, Gu, Jian, Hjalgrim, Henrik, Cozen, Wendy, Becker, Nikolaus, Teras, Lauren R, Spinelli, John J, Turner, Jenny, Zhang, Yawei, Purdue, Mark P, Giles, Graham G, Kelly, Rachel S, Zeleniuch-Jacquotte, Anne, Ennas, Maria Grazia, Monnereau, Alain, Bertrand, Kimberly A, Albanes, Demetrius, Lightfoot, Tracy, Yeager, Meredith, Chung, Charles C, Burdett, Laurie, Hutchinson, Amy, Lawrence, Charles, Montalvan, Rebecca, Liang, Liming, Huang, Jinyan, Ma, Baoshan, Villano, Danylo J, Maria, Ann, Corines, Marina, Thomas, Tinu, Novak, Anne J, Dogan, Ahmet, Liebow, Mark, Thompson, Carrie A, Witzig, Thomas E, Habermann, Thomas M, Weiner, George J, Smith, Martyn T, Holly, Elizabeth A, Jackson, Rebecca D, Tinker, Lesley F, Ye, Yuanqing, Adami, Hans-Olov, Smedby, Karin E, De Roos, Anneclaire J, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, McKay, James, Staines, Anthony, Diver, W Ryan, Vajdic, Claire M, Armstrong, Bruce K, Kricker, Anne, Zheng, Tongzhang, Holford, Theodore R, Severi, Gianluca, Vineis, Paolo, Ferri, Giovanni M, Ricco, Rosalia, Miligi, Lucia, Clavel, Jacqueline, Giovannucci, Edward, Kraft, Peter, Virtamo, Jarmo, Smith, Alex, Kane, Eleanor, Roman, Eve, Chiu, Brian CH, Fraumeni, Joseph F, Wu, Xifeng, Cerhan, James R, Offit, Kenneth, and Chanock, Stephen J

Subjects
Humans, Membrane Glycoproteins, Computational Biology, Major Histocompatibility Complex, Genotype, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Lymphoma, B-Cell, Marginal Zone, Genome-Wide Association Study, Butyrophilins, Polymorphism, Single Nucleotide, Lymphoma, B-Cell, Marginal Zone
Abstract

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.

Published
2015

43. Whole Genome Sequencing Identifies CRISPLD2 as a Lung Function Gene in Children With Asthma

Author

Abe, Namiko, Abecasis, Goncalo, Albert, Christine, Palmer Allred, Nicholette (Nichole), Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Arking, Dan, Arnett, Donna K., Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Beaty, Terri, Becker, Diane, Becker, Lewis, Beer, Rebecca, Begum, Ferdouse, Beitelshees, Amber, Benjamin, Emelia, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Boerwinkle, Eric, Borecki, Ingrid, Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Bunting, Karen, Burchard, Esteban, Cardwell, Jonathan, Carty, Cara, Casaburi, Richard, Casella, James, Chaffin, Mark, Chang, Christy, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Chen, Yii-Der Ida, Cho, Michael H., Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, Das, Sayantan, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Do, Ron, Duan, Qing, Duggirala, Ravi, Durda, Peter, Dutcher, Susan, Eaton, Charles, Ekunwe, Lynette, Ellinor, Patrick, Emery, Leslie, Farber, Charles, Farnam, Leanna, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Yan, Gass, Margery, Gelb, Bruce, Geng, Xiaoqi (Priscilla), Germer, Soren, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Haessler, Jeff, Hall, Michael, Harris, Daniel, Hawley, Nicola, He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hokanson, John, Holly, Kramer, Hong, Elliott, Hoth, Karin, (Agnes) Hsiung, Chao, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Jhun, Min A., Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kachroo, Priyadarshini, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kathiresan, Sekar, Kaufman, Laura, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Krauter, Stephanie, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Seunggeun Shawn, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Yun, Lin, Honghuang, Lin, Keng Han, Liu, Simin, Liu, Yongmei, Loos, Ruth, Lubitz, Steven, Lunetta, Kathryn, Luo, James, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manson, JoAnn, Margolin, Lauren, Martin, Lisa, Mathai, Susan, Mathias, Rasika, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, Mei, Hao, Meyers, Deborah A., Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L., Mitchell, Braxton, Montasser, May E., Musani, Solomon, Mwasongwe, Stanford, Mychaleckyj, Josyf C., Nadkarni, Girish, Naik, Rakhi, Natarajan, Pradeep, Nekhai, Sergei, Nickerson, Deborah, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Pankow, James, Papanicolaou, George, Parker, Margaret, Parsa, Afshin, Penchev, Sara, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S., Phillips, Sam, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Prokopenko, Dmitry, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Ramachandran, Vasan, Rao, D.C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Regan, Elizabeth, Reiner, Alex, Rice, Ken, Rich, Stephen, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sakornsakolpat, Phuwanat, Salimi, Shabnam, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay, Scheller, Christopher, Schmidt, Ellen, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sheehan, Vivien, Shetty, Amol, Shetty, Aniket, Sheu, Wayne Hui-Heng, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne, Streeten, Elizabeth, Sung, Yun Ju, Su-Lasky, Jessica, Sylvia, Jody, Szpiro, Adam, Sztalryd, Carole, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Tinker, Lesley, Tirschwell, David, Tiwari, Hemant, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wan, Emily, Wang, Fei Fei, Watson, Karol, Weeks, Daniel E., Weir, Bruce, Weiss, Scott, Weng, Lu-Chen, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Wong, Quenna, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yang, Rongze, Zaghloul, Norann, Zekavat, Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zheng, Xiuwen, Zhi, Degui, Zhou, Xiang, Zody, Michael, Zoellner, Sebastian, Hecker, Julian, Chawes, Bo L., Ahluwalia, Tarunveer S., Kelly, Rachel S., Chu, Su H., Virkud, Yamini V., Huang, Mengna, Barnes, Kathleen C., Burchard, Esteban G., Eng, Celeste, Hu, Donglei, Celedón, Juan C., Levin, Albert M., Gui, Hongsheng, Forno, Erick, Mak, Angel C.Y., Avila, Lydiana, Soto-Quiros, Manuel E., Cloutier, Michelle M., Acosta-Pérez, Edna, Canino, Glorisa, Bønnelykke, Klaus, Bisgaard, Hans, Raby, Benjamin A., Weiss, Scott T., and Lasky-Su, Jessica A.

Published
2019
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46. Author Correction: Metabolomic profiling reveals extensive adrenal suppression due to inhaled corticosteroid therapy in asthma

Author

Kachroo, Priyadarshini, Stewart, Isobel D., Kelly, Rachel S., Stav, Meryl, Mendez, Kevin, Dahlin, Amber, Soeteman, Djøra I., Chu, Su H., Huang, Mengna, Cote, Margaret, Knihtilä, Hanna M., Lee-Sarwar, Kathleen, McGeachie, Michael, Wang, Alberta, Wu, Ann Chen, Virkud, Yamini, Zhang, Pei, Wareham, Nicholas J., Karlson, Elizabeth W., Wheelock, Craig E., Clish, Clary, Weiss, Scott T., Langenberg, Claudia, and Lasky-Su, Jessica A.

Published
2022
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47. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Author

Cerhan, James R, Berndt, Sonja I, Vijai, Joseph, Ghesquières, Hervé, McKay, James, Wang, Sophia S, Wang, Zhaoming, Yeager, Meredith, Conde, Lucia, de Bakker, Paul IW, Nieters, Alexandra, Cox, David, Burdett, Laurie, Monnereau, Alain, Flowers, Christopher R, De Roos, Anneclaire J, Brooks-Wilson, Angela R, Lan, Qing, Severi, Gianluca, Melbye, Mads, Gu, Jian, Jackson, Rebecca D, Kane, Eleanor, Teras, Lauren R, Purdue, Mark P, Vajdic, Claire M, Spinelli, John J, Giles, Graham G, Albanes, Demetrius, Kelly, Rachel S, Zucca, Mariagrazia, Bertrand, Kimberly A, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Hutchinson, Amy, Zhi, Degui, Habermann, Thomas M, Link, Brian K, Novak, Anne J, Dogan, Ahmet, Asmann, Yan W, Liebow, Mark, Thompson, Carrie A, Ansell, Stephen M, Witzig, Thomas E, Weiner, George J, Veron, Amelie S, Zelenika, Diana, Tilly, Hervé, Haioun, Corinne, Molina, Thierry Jo, Hjalgrim, Henrik, Glimelius, Bengt, Adami, Hans-Olov, Bracci, Paige M, Riby, Jacques, Smith, Martyn T, Holly, Elizabeth A, Cozen, Wendy, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Tinker, Lesley F, North, Kari E, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, Lightfoot, Tracy, Crouch, Simon, Smith, Alex, Roman, Eve, Diver, W Ryan, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Villano, Danylo J, Zheng, Tongzhang, Zhang, Yawei, Holford, Theodore R, Kricker, Anne, Turner, Jenny, Southey, Melissa C, Clavel, Jacqueline, Virtamo, Jarmo, Weinstein, Stephanie, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Trichopoulos, Dimitrios, Vermeulen, Roel CH, Boeing, Heiner, Tjonneland, Anne, Angelucci, Emanuele, Di Lollo, Simonetta, Rais, Marco, and Birmann, Brenda M

Subjects
Human Genome, Rare Diseases, Genetics, Cancer, Hematology, Lymphoma, Aetiology, 2.1 Biological and endogenous factors, Chromosome Mapping, Computational Biology, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Likelihood Functions, Lymphoma, Large B-Cell, Diffuse, Polymorphism, Single Nucleotide, Quantitative Trait Loci, White People, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

Published
2014

48. Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

Author

Skibola, Christine F, Berndt, Sonja I, Vijai, Joseph, Conde, Lucia, Wang, Zhaoming, Yeager, Meredith, de Bakker, Paul IW, Birmann, Brenda M, Vajdic, Claire M, Foo, Jia-Nee, Bracci, Paige M, Vermeulen, Roel CH, Slager, Susan L, de Sanjose, Silvia, Wang, Sophia S, Linet, Martha S, Salles, Gilles, Lan, Qing, Severi, Gianluca, Hjalgrim, Henrik, Lightfoot, Tracy, Melbye, Mads, Gu, Jian, Ghesquières, Hervé, Link, Brian K, Morton, Lindsay M, Holly, Elizabeth A, Smith, Alex, Tinker, Lesley F, Teras, Lauren R, Kricker, Anne, Becker, Nikolaus, Purdue, Mark P, Spinelli, John J, Zhang, Yawei, Giles, Graham G, Vineis, Paolo, Monnereau, Alain, Bertrand, Kimberly A, Albanes, Demetrius, Zeleniuch-Jacquotte, Anne, Gabbas, Attilio, Chung, Charles C, Burdett, Laurie, Hutchinson, Amy, Lawrence, Charles, Montalvan, Rebecca, Liang, Liming, Huang, Jinyan, Ma, Baoshan, Liu, Jianjun, Adami, Hans-Olov, Glimelius, Bengt, Ye, Yuanqing, Nowakowski, Grzegorz S, Dogan, Ahmet, Thompson, Carrie A, Habermann, Thomas M, Novak, Anne J, Liebow, Mark, Witzig, Thomas E, Weiner, George J, Schenk, Maryjean, Hartge, Patricia, De Roos, Anneclaire J, Cozen, Wendy, Zhi, Degui, Akers, Nicholas K, Riby, Jacques, Smith, Martyn T, Lacher, Mortimer, Villano, Danylo J, Maria, Ann, Roman, Eve, Kane, Eleanor, Jackson, Rebecca D, North, Kari E, Diver, W Ryan, Turner, Jenny, Armstrong, Bruce K, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, McKay, James, Brooks-Wilson, Angela R, Zheng, Tongzhang, Holford, Theodore R, Chamosa, Saioa, Kaaks, Rudolph, Kelly, Rachel S, Ohlsson, Bodil, Travis, Ruth C, Weiderpass, Elisabete, Clavel, Jacqueline, Giovannucci, Edward, Kraft, Peter, and Virtamo, Jarmo

Subjects
Hematology, Cancer, Clinical Research, Human Genome, Lymphoma, Genetics, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Alleles, Biomarkers, Tumor, Case-Control Studies, Chromosomes, Human, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA Antigens, Haplotypes, Humans, Lymphoma, Follicular, Polymorphism, Single Nucleotide, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

Published
2014

50. Sphingolipid classes and the interrelationship with pediatric asthma and asthma risk factors

Author

Chen, Yulu, primary, Checa, Antonio, additional, Zhang, Pei, additional, Huang, Mengna, additional, Kelly, Rachel S., additional, Kim, Min, additional, Chen, Yih‐Chieh S., additional, Lee‐Sarwar, Kathleen A., additional, Prince, Nicole, additional, Mendez, Kevin M., additional, Begum, Sofina, additional, Kachroo, Priyadarshini, additional, Chu, Su H., additional, Stokholm, Jakob, additional, Bønnelykke, Klaus, additional, Litonjua, Augusto A., additional, Bisgaard, Hans, additional, Weiss, Scott T., additional, Chawes, Bo L., additional, Wheelock, Craig E., additional, and Lasky‐Su, Jessica A., additional

Published
2023
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