Search

Your search keyword '"Barfield, Richard"' showing total 197 results
Start Over Author "Barfield, Richard"
197 results on '"Barfield, Richard"'

2. Late gene expression-deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV

Author

Hansen, Scott G, Womack, Jennie L, Perez, Wilma, Schmidt, Kimberli A, Marshall, Emily, Iyer, Ravi F, Cleveland-Rubeor, Hillary, Otero, Claire E, Taher, Husam, Burgt, Nathan H Vande, Barfield, Richard, Randall, Kurt T, Morrow, David, Hughes, Colette M, Selseth, Andrea N, Gilbride, Roxanne M, Ford, Julia C, Caposio, Patrizia, Tarantal, Alice, Chan, Cliburn, Malouli, Daniel, Barry, Peter A, Permar, Sallie R, Picker, Louis J, and Frueh, Klaus

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Vaccine Related (AIDS), Genetics, Vaccine Related, Biotechnology, Immunization, Prevention, Good Health and Well Being, Animals, Humans, Cytomegalovirus, Simian Immunodeficiency Virus, Macaca mulatta, Gene Expression, Simian immunodeficiency virus, AIDS vaccine, AIDS/HIV, T cells, Virology, Biomedical and clinical sciences, Health sciences
Abstract

Rhesus cytomegalovirus-based (RhCMV-based) vaccine vectors induce immune responses that protect ~60% of rhesus macaques (RMs) from SIVmac239 challenge. This efficacy depends on induction of effector memory-based (EM-biased) CD8+ T cells recognizing SIV peptides presented by major histocompatibility complex-E (MHC-E) instead of MHC-Ia. The phenotype, durability, and efficacy of RhCMV/SIV-elicited cellular immune responses were maintained when vector spread was severely reduced by deleting the antihost intrinsic immunity factor phosphoprotein 71 (pp71). Here, we examined the impact of an even more stringent attenuation strategy on vector-induced immune protection against SIV. Fusion of the FK506-binding protein (FKBP) degradation domain to Rh108, the orthologue of the essential human CMV (HCMV) late gene transcription factor UL79, generated RhCMV/SIV vectors that conditionally replicate only when the FK506 analog Shield-1 is present. Despite lacking in vivo dissemination and reduced innate and B cell responses to vaccination, Rh108-deficient 68-1 RhCMV/SIV vectors elicited high-frequency, durable, EM-biased, SIV-specific T cell responses in RhCMV-seropositive RMs at doses of ≥ 1 × 106 PFU. Strikingly, elicited CD8+ T cells exclusively targeted MHC-Ia-restricted epitopes and failed to protect against SIVmac239 challenge. Thus, Rh108-dependent late gene expression is required for both induction of MHC-E-restricted T cells and protection against SIV.

Published
2023

7. Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival.

Author

Zaidi, Syed H, Harrison, Tabitha A, Phipps, Amanda I, Steinfelder, Robert, Trinh, Quang M, Qu, Conghui, Banbury, Barbara L, Georgeson, Peter, Grasso, Catherine S, Giannakis, Marios, Adams, Jeremy B, Alwers, Elizabeth, Amitay, Efrat L, Barfield, Richard T, Berndt, Sonja I, Borozan, Ivan, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D, Cao, Yin, Chan, Andrew T, Chang-Claude, Jenny, Connolly, Charles M, Drew, David A, Farris, Alton Brad, Figueiredo, Jane C, French, Amy J, Fuchs, Charles S, Garraway, Levi A, Gruber, Steve, Guinter, Mark A, Hamilton, Stanley R, Harlid, Sophia, Heisler, Lawrence E, Hidaka, Akihisa, Hopper, John L, Huang, Wen-Yi, Huyghe, Jeroen R, Jenkins, Mark A, Krzyzanowski, Paul M, Lemire, Mathieu, Lin, Yi, Luo, Xuemei, Mardis, Elaine R, McPherson, John D, Miller, Jessica K, Moreno, Victor, Mu, Xinmeng Jasmine, Nishihara, Reiko, Papadopoulos, Nickolas, Pasternack, Danielle, Quist, Michael J, Rafikova, Adilya, Reid, Emma EG, Shinbrot, Eve, Shirts, Brian H, Stein, Lincoln D, Teney, Cherie D, Timms, Lee, Um, Caroline Y, Van Guelpen, Bethany, Van Tassel, Megan, Wang, Xiaolong, Wheeler, David A, Yung, Christina K, Hsu, Li, Ogino, Shuji, Gsur, Andrea, Newcomb, Polly A, Gallinger, Steven, Hoffmeister, Michael, Campbell, Peter T, Thibodeau, Stephen N, Sun, Wei, Hudson, Thomas J, and Peters, Ulrike

Abstract

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.

Published
2020

8. Epigenome-wide association analysis of daytime sleepiness in the Multi-Ethnic Study of Atherosclerosis reveals African-American-specific associations

Author

Barfield, Richard, Wang, Heming, Liu, Yongmei, Brody, Jennifer A, Swenson, Brenton, Li, Ruitong, Bartz, Traci M, Sotoodehnia, Nona, Chen, Yii-der I, Cade, Brian E, Chen, Han, Patel, Sanjay R, Zhu, Xiaofeng, Gharib, Sina A, Johnson, W Craig, Rotter, Jerome I, Saxena, Richa, Purcell, Shaun, Lin, Xihong, Redline, Susan, and Sofer, Tamar

Subjects
Sleep Research, Genetics, Atherosclerosis, Aging, Human Genome, Good Health and Well Being, African Americans, Aged, DNA Methylation, Epigenome, Female, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Prevalence, Sleep, Sleep Wake Disorders, diversity, epigenetics, race/ethnic heterogeneity, excessive daytime sleepiness, sleep-wake, methylation, genomics, Black or African American, sleep–wake, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Study objectivesDaytime sleepiness is a consequence of inadequate sleep, sleep-wake control disorder, or other medical conditions. Population variability in prevalence of daytime sleepiness is likely due to genetic and biological factors as well as social and environmental influences. DNA methylation (DNAm) potentially influences multiple health outcomes. Here, we explored the association between DNAm and daytime sleepiness quantified by the Epworth Sleepiness Scale (ESS).MethodsWe performed multi-ethnic and ethnic-specific epigenome-wide association studies for DNAm and ESS in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 619) and the Cardiovascular Health Study (n = 483), with cross-study replication and meta-analysis. Genetic variants near ESS-associated DNAm were analyzed for methylation quantitative trait loci and followed with replication of genotype-sleepiness associations in the UK Biobank.ResultsIn MESA only, we detected four DNAm-ESS associations: one across all race/ethnic groups; three in African-Americans (AA) only. Two of the MESA AA associations, in genes KCTD5 and RXRA, nominally replicated in CHS (p-value < 0.05). In the AA meta-analysis, we detected 14 DNAm-ESS associations (FDR q-value < 0.05, top association p-value = 4.26 × 10-8). Three DNAm sites mapped to genes (CPLX3, GFAP, and C7orf50) with biological relevance. We also found evidence for associations with DNAm sites in RAI1, a gene associated with sleep and circadian phenotypes. UK Biobank follow-up analyses detected SNPs in RAI1, RXRA, and CPLX3 with nominal sleepiness associations.ConclusionsWe identified methylation sites in multiple genes possibly implicated in daytime sleepiness. Most significant DNAm-ESS associations were specific to AA. Future work is needed to identify mechanisms driving ancestry-specific methylation effects.

Published
2019

9. Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep

Author

Cade, Brian E, Chen, Han, Stilp, Adrienne M, Louie, Tin, Ancoli-Israel, Sonia, Arens, Raanan, Barfield, Richard, Below, Jennifer E, Cai, Jianwen, Conomos, Matthew P, Evans, Daniel S, Frazier-Wood, Alexis C, Gharib, Sina A, Gleason, Kevin J, Gottlieb, Daniel J, Hillman, David R, Johnson, W Craig, Lederer, David J, Lee, Jiwon, Loredo, Jose S, Mei, Hao, Mukherjee, Sutapa, Patel, Sanjay R, Post, Wendy S, Purcell, Shaun M, Ramos, Alberto R, Reid, Kathryn J, Rice, Ken, Shah, Neomi A, Sofer, Tamar, Taylor, Kent D, Thornton, Timothy A, Wang, Heming, Yaffe, Kristine, Zee, Phyllis C, Hanis, Craig L, Palmer, Lyle J, Rotter, Jerome I, Stone, Katie L, Tranah, Gregory J, Wilson, James G, Sunyaev, Shamil R, Laurie, Cathy C, Zhu, Xiaofeng, Saxena, Richa, Lin, Xihong, and Redline, Susan

Subjects
Genetics, Lung, Sleep Research, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Aged, Aged, 80 and over, Cell Adhesion Molecules, Neuronal, Computational Biology, Extracellular Matrix Proteins, Female, Gene Regulatory Networks, Genetic Variation, Genome-Wide Association Study, Hexokinase, Humans, Hypoxia, Interleukin-18 Receptor alpha Subunit, Male, Middle Aged, NLR Family, Pyrin Domain-Containing 3 Protein, Nerve Tissue Proteins, Oxygen, Oxyhemoglobins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reelin Protein, Serine Endopeptidases, Sleep, Sleep Apnea Syndromes, Young Adult, Developmental Biology
Abstract

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.

Published
2019

10. Association between germline variants and somatic mutations in colorectal cancer

Author

Barfield, Richard, Qu, Conghui, Steinfelder, Robert S., Zeng, Chenjie, Harrison, Tabitha A., Brezina, Stefanie, Buchanan, Daniel D., Campbell, Peter T., Casey, Graham, Gallinger, Steven, Giannakis, Marios, Gruber, Stephen B., Gsur, Andrea, Hsu, Li, Huyghe, Jeroen R., Moreno, Victor, Newcomb, Polly A., Ogino, Shuji, Phipps, Amanda I., Slattery, Martha L., Thibodeau, Stephen N., Trinh, Quang M., Toland, Amanda E., Hudson, Thomas J., Sun, Wei, Zaidi, Syed H., and Peters, Ulrike

Published
2022
Full Text
View/download PDF

11. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author

Wu, Lang, Shi, Wei, Long, Jirong, Guo, Xingyi, Michailidou, Kyriaki, Beesley, Jonathan, Bolla, Manjeet K, Shu, Xiao-Ou, Lu, Yingchang, Cai, Qiuyin, Al-Ejeh, Fares, Rozali, Esdy, Wang, Qin, Dennis, Joe, Li, Bingshan, Zeng, Chenjie, Feng, Helian, Gusev, Alexander, Barfield, Richard T, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Barrdahl, Myrto, Baynes, Caroline, Beckmann, Matthias W, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara Y, Burwinkel, Barbara, Caldés, Trinidad, Canzian, Federico, Carter, Brian D, Castelao, J Esteban, Chang-Claude, Jenny, Chen, Xiaoqing, Cheng, Ting-Yuan David, Christiansen, Hans, Clarke, Christine L, NBCS Collaborators, Collée, Margriet, Cornelissen, Sten, Couch, Fergus J, Cox, David, Cox, Angela, Cross, Simon S, Cunningham, Julie M, Czene, Kamila, Daly, Mary B, Devilee, Peter, Doheny, Kimberly F, Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Eccles, Diana M, Eilber, Ursula, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Fachal, Laura, Fasching, Peter A, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia M, Ghoussaini, Maya, Giles, Graham G, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hollestelle, Antoinette, Hoover, Robert N, Hopper, John L, and Huang, Guanmengqian

Subjects
Biological Sciences, Genetics, Cancer, Breast Cancer, Human Genome, Prevention, Women's Health, Cancer Genomics, Biotechnology, 2.1 Biological and endogenous factors, Generic health relevance, Breast Neoplasms, Case-Control Studies, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk, Transcriptome, NBCS Collaborators, kConFab/AOCS Investigators, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P

Published
2018

12. Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity

Author

Otero, Claire E., primary, Petkova, Sophia, additional, Ebermann, Martin, additional, Taher, Husam, additional, John, Nessy, additional, Hoffmann, Katja, additional, Davalos, Angel, additional, Mostrom, Matilda J, additional, Gilbride, Roxanne M, additional, Papen, Courtney, additional, Barber-Axthelm, Aaron, additional, Scheef, Elizabeth A., additional, Barfield, Richard, additional, Sprehe, Lesli M., additional, Kendall, Savannah, additional, Manuel, Tabitha D, additional, Vande Burgt, Nathan, additional, Chan, Cliburn, additional, Streblow, Daniel N., additional, Hansen, Scott G., additional, Denton, Michael, additional, Streblow, Zachary, additional, Kaur, Amitinder, additional, Permar, Sallie R, additional, Frueh, Klaus, additional, Hengel, Hartmut, additional, Malouli, Daniel, additional, and Kolb, Philipp, additional

Published
2024
Full Text
View/download PDF

13. A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery

Author

Eckhoff, Austin M., Connor, Ashton A., Thacker, Julie K. M., Blazer, Dan G., Moore, Harvey G., Scheri, Randall P., Lagoo-Deenadayalan, Sandhya A., Harpole, David H., Seymour, Keri A., Purves, J. Todd, Ravindra, Kadiyala V., Southerland, Kevin W., Rocke, Daniel J., Gilner, Jennifer B., Parker, Daniel C., Bain, James R., Muehlbauer, Michael J., Ilkayeva, Olga R., Corcoran, David L., Modliszewski, Jennifer L., Devos, Nicolas, Foster, Matthew W., Moseley, M. Arthur, Dressman, Holly K., Chan, Cliburn, Huebner, Janet L., Chasse, Scott, Stempora, Linda, Aschenbrenner, Mary E., Joshi, Mary-Beth, Hollister, Beth, Henao, Ricardo, Barfield, Richard T., Ellison, Mark A., Bailey, Sean, Woody, Stephen, Huang, Erich S., Kirk, Allan, and Hwang, E. Shelley

Published
2022
Full Text
View/download PDF

14. Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques

Author

Tuyishime, Marina, primary, Spreng, Rachel L., additional, Hueber, Brady, additional, Nohara, Junsuke, additional, Goodman, Derrick, additional, Chan, Cliburn, additional, Barfield, Richard, additional, Beck, Whitney E., additional, Jha, Shalini, additional, Asdell, Stephanie, additional, Wiehe, Kevin, additional, He, Max M., additional, Easterhoff, David, additional, Conley, Haleigh E., additional, Hoxie, Taylor, additional, Gurley, Thaddeus, additional, Jones, Caroline, additional, Adhikary, Nihar Deb, additional, Villinger, Francois, additional, Thomas, Rasmi, additional, Denny, Thomas N., additional, Moody, Michael Anthony, additional, Tomaras, Georgia D., additional, Pollara, Justin, additional, Reeves, R. Keith, additional, and Ferrari, Guido, additional

Published
2023
Full Text
View/download PDF

15. Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model

Author

Otero, Claire E., primary, Barfield, Richard, additional, Scheef, Elizabeth, additional, Nelson, Cody S., additional, Rodgers, Nicole, additional, Wang, Hsuan-Yuan, additional, Moström, Matilda J., additional, Manuel, Tabitha D., additional, Sass, Julian, additional, Schmidt, Kimberli, additional, Taher, Husam, additional, Papen, Courtney, additional, Sprehe, Lesli, additional, Kendall, Savannah, additional, Davalos, Angel, additional, Barry, Peter A., additional, Früh, Klaus, additional, Pollara, Justin, additional, Malouli, Daniel, additional, Chan, Cliburn, additional, Kaur, Amitinder, additional, and Permar, Sallie R., additional

Published
2023
Full Text
View/download PDF

17. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

Author

Wolpin, Brian M, Rizzato, Cosmeri, Kraft, Peter, Kooperberg, Charles, Petersen, Gloria M, Wang, Zhaoming, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Buring, Julie, Canzian, Federico, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Jacobs, Eric J, Kamineni, Aruna, Klein, Alison P, Kolonel, Laurence N, Kulke, Matthew H, Li, Donghui, Malats, Núria, Olson, Sara H, Risch, Harvey A, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetrius, Andreotti, Gabriella, Austin, Melissa A, Barfield, Richard, Basso, Daniela, Berndt, Sonja I, Boutron-Ruault, Marie-Christine, Brotzman, Michelle, Büchler, Markus W, Bueno-de-Mesquita, H Bas, Bugert, Peter, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Chung, Charles, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Funel, Niccola, Gaziano, J Michael, Giese, Nathalia A, Giovannucci, Edward L, Goggins, Michael, Gorman, Megan J, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Henderson, Brian E, Holly, Elizabeth A, Hu, Nan, Hunter, David J, Innocenti, Federico, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C, LaCroix, Andrea, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Nakamura, Yusuke, Oberg, Ann L, Owzar, Kouros, Patel, Alpa V, Peeters, Petra HM, Peters, Ulrike, Pezzilli, Raffaele, Piepoli, Ada, Porta, Miquel, Real, Francisco X, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Shu, Xiao-Ou, Silverman, Debra T, Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Taylor, Philip R, and Theodoropoulos, George E

Subjects
Cancer, Aged, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Pancreatic Neoplasms, Polymorphism, Single Nucleotide, White People, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

Published
2014

18. The pentameric complex is not required for vertical transmission of cytomegalovirus in seronegative pregnant rhesus macaques

Author

Wang, Hsuan-Yuan, primary, Taher, Husam, additional, Kreklywich, Craig N., additional, Schmidt, Kimberli A., additional, Scheef, Elizabeth A., additional, Barfield, Richard, additional, Otero, Claire E., additional, Valencia, Sarah M., additional, Crooks, Chelsea M., additional, Mirza, Anne, additional, Woods, Kelsey, additional, Burgt, Nathan Vande, additional, Kowalik, Timothy F., additional, Barry, Peter A., additional, Hansen, Scott G., additional, Tarantal, Alice F., additional, Chan, Cliburn, additional, Streblow, Daniel N., additional, Picker, Louis J., additional, Kaur, Amitinder, additional, Früh, Klaus, additional, Permar, Sallie R., additional, and Malouli, Daniel, additional

Published
2023
Full Text
View/download PDF

19. The pentameric complex is not required for vertical transmission of cytomegalovirus in seronegative pregnant rhesus macaques

Author

Wang, Hsuan-Yuan, Taher, Husam, Kreklywich, Craig N., Schmidt, Kimberli A., Scheef, Elizabeth A., Barfield, Richard, Otero, Claire E., Valencia, Sarah M., Crooks, Chelsea M., Mirza, Anne, Woods, Kelsey, Burgt, Nathan Vande, Kowalik, Timothy F., Barry, Peter A., Hansen, Scott G., Tarantal, Alice F., Chan, Cliburn, Streblow, Daniel N., Picker, Louis J., Kaur, Amitinder, Früh, Klaus, Permar, Sallie R., and Malouli, Daniel

Subjects
Article
Abstract

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neonatal neurological impairment but essential virological determinants of transplacental CMV transmission remain unclear. The pentameric complex (PC), composed of five subunits, glycoproteins H (gH), gL, UL128, UL130, and UL131A, is essential for efficient entry into non-fibroblast cells in vitro . Based on this role in cell tropism, the PC is considered a possible target for CMV vaccines and immunotherapies to prevent cCMV. To determine the role of the PC in transplacental CMV transmission in a non-human primate model of cCMV, we constructed a PC-deficient rhesus CMV (RhCMV) by deleting the homologues of the HCMV PC subunits UL128 and UL130 and compared congenital transmission to PC-intact RhCMV in CD4+ T cell-depleted or immunocompetent RhCMV-seronegative, pregnant rhesus macaques (RM). Surprisingly, we found that the transplacental transmission rate was similar for PC-intact and PC-deleted RhCMV based on viral genomic DNA detection in amniotic fluid. Moreover, PC-deleted and PC-intact RhCMV acute infection led to similar peak maternal plasma viremia. However, there was less viral shedding in maternal urine and saliva and less viral dissemination in fetal tissues in the PC-deleted group. As expected, dams inoculated with PC-deleted RhCMV demonstrated lower plasma IgG binding to PC-intact RhCMV virions and soluble PC, as well as reduced neutralization of PC-dependent entry of the PC-intact RhCMV isolate UCD52 into epithelial cells. In contrast, binding to gH expressed on the cell surface and neutralization of entry into fibroblasts by the PC-intact RhCMV was higher for dams infected with PC-deleted RhCMV compared to those infected with PC-intact RhCMV. Our data demonstrates that the PC is dispensable for transplacental CMV infection in our non-human primate model. ONE SENTENCE SUMMARY: Congenital CMV transmission frequency in seronegative rhesus macaques is not affected by the deletion of the viral pentameric complex.

Published
2023

20. Supplementary Table S7 from Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies

Author

Hidaka, Akihisa, primary, Harrison, Tabitha A., primary, Cao, Yin, primary, Sakoda, Lori C., primary, Barfield, Richard, primary, Giannakis, Marios, primary, Song, Mingyang, primary, Phipps, Amanda I., primary, Figueiredo, Jane C., primary, Zaidi, Syed H., primary, Toland, Amanda E., primary, Amitay, Efrat L., primary, Berndt, Sonja I., primary, Borozan, Ivan, primary, Chan, Andrew T., primary, Gallinger, Steven, primary, Gunter, Marc J., primary, Guinter, Mark A., primary, Harlid, Sophia, primary, Hampel, Heather, primary, Jenkins, Mark A., primary, Lin, Yi, primary, Moreno, Victor, primary, Newcomb, Polly A., primary, Nishihara, Reiko, primary, Ogino, Shuji, primary, Obón-Santacana, Mireia, primary, Parfrey, Patrick S., primary, Potter, John D., primary, Slattery, Martha L., primary, Steinfelder, Robert S., primary, Um, Caroline Y., primary, Wang, Xiaoliang, primary, Woods, Michael O., primary, Van Guelpen, Bethany, primary, Thibodeau, Stephen N., primary, Hoffmeister, Michael, primary, Sun, Wei, primary, Hsu, Li, primary, Buchanan, Daniel D., primary, Campbell, Peter T., primary, and Peters, Ulrike, primary

Published
2023
Full Text
View/download PDF

21. Supplementary Text from Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies

Author

Hidaka, Akihisa, primary, Harrison, Tabitha A., primary, Cao, Yin, primary, Sakoda, Lori C., primary, Barfield, Richard, primary, Giannakis, Marios, primary, Song, Mingyang, primary, Phipps, Amanda I., primary, Figueiredo, Jane C., primary, Zaidi, Syed H., primary, Toland, Amanda E., primary, Amitay, Efrat L., primary, Berndt, Sonja I., primary, Borozan, Ivan, primary, Chan, Andrew T., primary, Gallinger, Steven, primary, Gunter, Marc J., primary, Guinter, Mark A., primary, Harlid, Sophia, primary, Hampel, Heather, primary, Jenkins, Mark A., primary, Lin, Yi, primary, Moreno, Victor, primary, Newcomb, Polly A., primary, Nishihara, Reiko, primary, Ogino, Shuji, primary, Obón-Santacana, Mireia, primary, Parfrey, Patrick S., primary, Potter, John D., primary, Slattery, Martha L., primary, Steinfelder, Robert S., primary, Um, Caroline Y., primary, Wang, Xiaoliang, primary, Woods, Michael O., primary, Van Guelpen, Bethany, primary, Thibodeau, Stephen N., primary, Hoffmeister, Michael, primary, Sun, Wei, primary, Hsu, Li, primary, Buchanan, Daniel D., primary, Campbell, Peter T., primary, and Peters, Ulrike, primary

Published
2023
Full Text
View/download PDF

22. Multivalent Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccines Demonstrate a Greater Breadth in T cell but not Antibody Responses

Author

Permar, Sallie, primary, Wang, Hsuan-Yuan, additional, Li, Leike, additional, Nelson, Cody, additional, Barfield, Richard, additional, Valencia, Sarah, additional, Chan, Cliburn, additional, Muramatsu, Hiromi, additional, Lin, Paulo, additional, Pardi, Norbert, additional, An, Zhiqiang, additional, and Weissman, Drew, additional

Published
2022
Full Text
View/download PDF

23. Multivalent Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccines Demonstrate a Greater Breadth in T cell but not Antibody Responses

Author

Wang, Hsuan-Yuan (Sherry), primary, Li, Leike, additional, Nelson, Cody S., additional, Barfield, Richard, additional, Valencia, Sarah, additional, Chan, Cliburn, additional, Muramatsu, Hiromi, additional, Lin, Paulo J.C., additional, Pardi, Norbert, additional, An, Zhiqiang, additional, Weissman, Drew, additional, and Permar, Sallie R., additional

Published
2022
Full Text
View/download PDF

25. Self-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation

Author

Chen, Jui-Lin, primary, Fries, Chelsea N., additional, Berendam, Stella J., additional, Rodgers, Nicole S., additional, Roe, Emily F., additional, Wu, Yaoying, additional, Li, Shuk Hang, additional, Jain, Rishabh, additional, Watts, Brian, additional, Eudailey, Joshua, additional, Barfield, Richard, additional, Chan, Cliburn, additional, Moody, M. Anthony, additional, Saunders, Kevin O., additional, Pollara, Justin, additional, Permar, Sallie R., additional, Collier, Joel H., additional, and Fouda, Genevieve G., additional

Published
2022
Full Text
View/download PDF

26. Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus

Author

Harnois, Melissa J, primary, Dennis, Maria, additional, Stöhr, Dagmar, additional, Valencia, Sarah M, additional, Rodgers, Nicole, additional, Semmes, Eleanor C, additional, Webster, Helen S, additional, Jenks, Jennifer A, additional, Barfield, Richard, additional, Pollara, Justin, additional, Chan, Cliburn, additional, Sinzger, Christian, additional, and Permar, Sallie R, additional

Published
2022
Full Text
View/download PDF

27. Elite neutralizers of human cytomegalovirus are characterized by high magnitude plasma IgG responses against multiple glycoprotein complexes

Author

Harnois, Melissa J., primary, Dennis, Maria, additional, Stöhr, Dagmar, additional, Valencia, Sarah M., additional, Rodgers, Nicole, additional, Semmes, Eleanor C., additional, Webster, Helen S., additional, Jenks, Jennifer A., additional, Barfield, Richard, additional, Pollara, Justin, additional, Chan, Cliburn, additional, Sinzger, Christian, additional, and Permar, Sallie R., additional

Published
2022
Full Text
View/download PDF

28. Mouse model implicates GNB3 duplication in a childhood obesity syndrome

Author

Unique Rare Chromosome Disorder Support Group, Goldlust, Ian S., Hermetz, Karen E., Catalano, Lisa M., Barfield, Richard T., Cozad, Rebecca, Wynn, Grace, Ozdemir, Alev Cagla, Conneely, Karen N., Mulle, Jennifer G., Dharamrup, Shikha, Hegde, Madhuri R., Kim, Katherine H., Angle, Brad, Colley, Alison, Webb, Amy E., Thorland, Erik C., Ellison, Jay W., Rosenfeld, Jill A., Ballif, Blake C., Shaffer, Lisa G., Demmer, Laurie A., and Rudd, M. Katharine

Published
2013

29. Genetic Regulation of DNA Methylation Yields Novel Discoveries in GWAS of Colorectal Cancer

Author

Barfield, Richard, primary, Huyghe, Jeroen R., additional, Lemire, Mathieu, additional, Dong, Xinyuan, additional, Su, Yu-Ru, additional, Brezina, Stefanie, additional, Buchanan, Daniel D., additional, Figueiredo, Jane C., additional, Gallinger, Steven, additional, Giannakis, Marios, additional, Gsur, Andrea, additional, Gunter, Marc J., additional, Hampel, Heather, additional, Harrison, Tabitha A., additional, Hopper, John L., additional, Hudson, Thomas J., additional, Li, Christopher I., additional, Moreno, Victor, additional, Newcomb, Polly A., additional, Pai, Rish K., additional, Pharoah, Paul D.P., additional, Phipps, Amanda I., additional, Qu, Conghui, additional, Steinfelder, Robert S., additional, Sun, Wei, additional, Win, Aung Ko, additional, Zaidi, Syed H., additional, Campbell, Peter T., additional, Peters, Ulrike, additional, and Hsu, Li, additional

Published
2022
Full Text
View/download PDF

31. Genetic architectures of proximal and distal colorectal cancer are partly distinct

Author

Huyghe, Jeroen R. Harrison, Tabitha A. Bien, Stephanie A. and Hampel, Heather Figueiredo, Jane C. Schmit, Stephanie L. and Conti, V, David Chen, Sai Qu, Conghui Lin, Yi Barfield, Richard Baron, John A. Cross, Amanda J. Diergaarde, Brenda and Duggan, David Harlid, Sophia Imaz, Liher Kang, Hyun Min and Levine, David M. Perduca, Vittorio Perez-Cornago, Aurora and Sakoda, Lori C. Schumacher, Fredrick R. Slattery, Martha L. and Toland, Amanda E. van Duijnhoven, Franzel J. B. Van Guelpen, Bethany Agudo, Antonio Albanes, Demetrius Alonso, M. Henar and Anderson, Kristin Arnau-Collell, Coral Arndt, Volker and Banbury, Barbara L. Bassik, Michael C. Berndt, I, Sonja and Bezieau, Stephane Bishop, D. Timothy Boehm, Juergen Boeing, Heiner Boutron-Ruault, Marie-Christine Brenner, Hermann and Brezina, Stefanie Buch, Stephan Buchanan, Daniel D. and Burnett-Hartman, Andrea Caan, Bette J. Campbell, Peter T. and Carr, Prudence R. Castells, Antoni Castellvi-Bel, Sergi and Chan, Andrew T. Chang-Claude, Jenny Chanock, Stephen J. and Curtis, Keith R. de la Chapelle, Albert Easton, Douglas F. and English, Dallas R. Feskens, Edith J. M. Gala, Manish and Gallinger, Steven J. Gauderman, W. James Giles, Graham G. and Goodman, Phyllis J. Grady, William M. Grove, John S. Gsur, Andrea Gunter, Marc J. Haile, Robert W. Hampe, Jochen and Hoffmeister, Michael Hopper, John L. Hsu, Wan-Ling Huang, Wen-Yi Hudson, Thomas J. Jenab, Mazda Jenkins, Mark A. and Joshi, Amit D. Keku, Temitope O. Kooperberg, Charles Kuhn, Tilman Kury, Sebastien Le Marchand, Loic Lejbkowicz, Flavio and Li, I, Christopher Li, Li Lieb, Wolfgang Lindblom, Annika Lindor, Noralane M. Mannisto, Satu Markowitz, Sanford D. Milne, Roger L. Moreno, Lorena Murphy, Neil Nassir, Rami Offit, Kenneth Ogino, Shuji Panico, Salvatore and Parfrey, Patrick S. Pearlman, Rachel Pharoah, Paul D. P. and Phipps, I, Amanda Platz, Elizabeth A. Potter, John D. and Prentice, Ross L. Qi, Lihong Raskin, Leon Rennert, Gad and Rennert, Hedy S. Riboli, Elio Schafmayer, Clemens Schoen, Robert E. Seminara, Daniela Song, Mingyang Su, Yu-Ru and Tangen, Catherine M. Thibodeau, Stephen N. Thomas, Duncan C. and Trichopoulou, Antonia Ulrich, Cornelia M. Visvanathan, Kala and Vodicka, Pavel Vodickova, Ludmila Vymetalkova, Veronika and Weigl, Korbinian Weinstein, Stephanie J. White, Emily Wolk, Alicja Woods, Michael O. Wu, Anna H. Abecasis, Goncalo R. and Nickerson, Deborah A. Scacheri, Peter C. Kundaje, Anshul and Casey, Graham Gruber, Stephen B. Hsu, Li Moreno, Victor and Hayes, Richard B. Newcomb, Polly A. Peters, Ulrike

Subjects
digestive system diseases
Abstract

Objective An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. Design To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. Results We identified 13 loci that reached genome-wide significance (p

Published
2021

33. Genetic architectures of proximal and distal colorectal cancer are partly distinct

Author

Huyghe, Jeroen R, primary, Harrison, Tabitha A, additional, Bien, Stephanie A, additional, Hampel, Heather, additional, Figueiredo, Jane C, additional, Schmit, Stephanie L, additional, Conti, David V, additional, Chen, Sai, additional, Qu, Conghui, additional, Lin, Yi, additional, Barfield, Richard, additional, Baron, John A, additional, Cross, Amanda J, additional, Diergaarde, Brenda, additional, Duggan, David, additional, Harlid, Sophia, additional, Imaz, Liher, additional, Kang, Hyun Min, additional, Levine, David M, additional, Perduca, Vittorio, additional, Perez-Cornago, Aurora, additional, Sakoda, Lori C, additional, Schumacher, Fredrick R, additional, Slattery, Martha L, additional, Toland, Amanda E, additional, van Duijnhoven, Fränzel J B, additional, Van Guelpen, Bethany, additional, Agudo, Antonio, additional, Albanes, Demetrius, additional, Alonso, M Henar, additional, Anderson, Kristin, additional, Arnau-Collell, Coral, additional, Arndt, Volker, additional, Banbury, Barbara L, additional, Bassik, Michael C, additional, Berndt, Sonja I, additional, Bézieau, Stéphane, additional, Bishop, D Timothy, additional, Boehm, Juergen, additional, Boeing, Heiner, additional, Boutron-Ruault, Marie-Christine, additional, Brenner, Hermann, additional, Brezina, Stefanie, additional, Buch, Stephan, additional, Buchanan, Daniel D, additional, Burnett-Hartman, Andrea, additional, Caan, Bette J, additional, Campbell, Peter T, additional, Carr, Prudence R, additional, Castells, Antoni, additional, Castellví-Bel, Sergi, additional, Chan, Andrew T, additional, Chang-Claude, Jenny, additional, Chanock, Stephen J, additional, Curtis, Keith R, additional, de la Chapelle, Albert, additional, Easton, Douglas F, additional, English, Dallas R, additional, Feskens, Edith J M, additional, Gala, Manish, additional, Gallinger, Steven J, additional, Gauderman, W James, additional, Giles, Graham G, additional, Goodman, Phyllis J, additional, Grady, William M, additional, Grove, John S, additional, Gsur, Andrea, additional, Gunter, Marc J, additional, Haile, Robert W, additional, Hampe, Jochen, additional, Hoffmeister, Michael, additional, Hopper, John L, additional, Hsu, Wan-Ling, additional, Huang, Wen-Yi, additional, Hudson, Thomas J, additional, Jenab, Mazda, additional, Jenkins, Mark A, additional, Joshi, Amit D, additional, Keku, Temitope O, additional, Kooperberg, Charles, additional, Kühn, Tilman, additional, Küry, Sébastien, additional, Le Marchand, Loic, additional, Lejbkowicz, Flavio, additional, Li, Christopher I, additional, Li, Li, additional, Lieb, Wolfgang, additional, Lindblom, Annika, additional, Lindor, Noralane M, additional, Männistö, Satu, additional, Markowitz, Sanford D, additional, Milne, Roger L, additional, Moreno, Lorena, additional, Murphy, Neil, additional, Nassir, Rami, additional, Offit, Kenneth, additional, Ogino, Shuji, additional, Panico, Salvatore, additional, Parfrey, Patrick S, additional, Pearlman, Rachel, additional, Pharoah, Paul D P, additional, Phipps, Amanda I, additional, Platz, Elizabeth A, additional, Potter, John D, additional, Prentice, Ross L, additional, Qi, Lihong, additional, Raskin, Leon, additional, Rennert, Gad, additional, Rennert, Hedy S, additional, Riboli, Elio, additional, Schafmayer, Clemens, additional, Schoen, Robert E, additional, Seminara, Daniela, additional, Song, Mingyang, additional, Su, Yu-Ru, additional, Tangen, Catherine M, additional, Thibodeau, Stephen N, additional, Thomas, Duncan C, additional, Trichopoulou, Antonia, additional, Ulrich, Cornelia M, additional, Visvanathan, Kala, additional, Vodicka, Pavel, additional, Vodickova, Ludmila, additional, Vymetalkova, Veronika, additional, Weigl, Korbinian, additional, Weinstein, Stephanie J, additional, White, Emily, additional, Wolk, Alicja, additional, Woods, Michael O, additional, Wu, Anna H, additional, Abecasis, Goncalo R, additional, Nickerson, Deborah A, additional, Scacheri, Peter C, additional, Kundaje, Anshul, additional, Casey, Graham, additional, Gruber, Stephen B, additional, Hsu, Li, additional, Moreno, Victor, additional, Hayes, Richard B, additional, Newcomb, Polly A, additional, and Peters, Ulrike, additional

Published
2021
Full Text
View/download PDF

34. Reduced plasmablast frequency is associated with seronegative myasthenia gravis

Author

Guptill, Jeffrey T., primary, Barfield, Richard, additional, Chan, Cliburn, additional, Russo, Melissa A., additional, Emmett, Doug, additional, Raja, Shruti, additional, Massey, Janice M., additional, Juel, Vern C., additional, Hobson‐Webb, Lisa D., additional, Gable, Karissa L., additional, Gonzalez, Natalia, additional, Hammett, Alex, additional, Howard, James F., additional, Chopra, Manisha, additional, Kaminski, Henry J., additional, Siddiqi, Zaeem A., additional, Migdal, Mattingly, additional, and Yi, John S., additional

Published
2020
Full Text
View/download PDF

35. Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies

Author

Hidaka, Akihisa, primary, Harrison, Tabitha A., additional, Cao, Yin, additional, Sakoda, Lori C., additional, Barfield, Richard, additional, Giannakis, Marios, additional, Song, Mingyang, additional, Phipps, Amanda I., additional, Figueiredo, Jane C., additional, Zaidi, Syed H., additional, Toland, Amanda E., additional, Amitay, Efrat L., additional, Berndt, Sonja I., additional, Borozan, Ivan, additional, Chan, Andrew T., additional, Gallinger, Steven, additional, Gunter, Marc J., additional, Guinter, Mark A., additional, Harlid, Sophia, additional, Hampel, Heather, additional, Jenkins, Mark A., additional, Lin, Yi, additional, Moreno, Victor, additional, Newcomb, Polly A., additional, Nishihara, Reiko, additional, Ogino, Shuji, additional, Obón-Santacana, Mireia, additional, Parfrey, Patrick S., additional, Potter, John D., additional, Slattery, Martha L., additional, Steinfelder, Robert S., additional, Um, Caroline Y., additional, Wang, Xiaoliang, additional, Woods, Michael O., additional, Van Guelpen, Bethany, additional, Thibodeau, Stephen N., additional, Hoffmeister, Michael, additional, Sun, Wei, additional, Hsu, Li, additional, Buchanan, Daniel D., additional, Campbell, Peter T., additional, and Peters, Ulrike, additional

Published
2020
Full Text
View/download PDF

36. Large-Scale Hypothesis Testing for Causal Mediation Effects with Applications in Genome-wide Epigenetic Studies.

Author

Liu, Zhonghua, Shen, Jincheng, Barfield, Richard, Schwartz, Joel, Baccarelli, Andrea A., and Lin, Xihong

Subjects
FALSE discovery rate, MEDIATION (Statistics), STATISTICAL hypothesis testing, FALSE positive error, EPIGENOMICS, NULL hypothesis, INFERENTIAL statistics, EPIGENETICS
Abstract

In genome-wide epigenetic studies, it is of great scientific interest to assess whether the effect of an exposure on a clinical outcome is mediated through DNA methylations. However, statistical inference for causal mediation effects is challenged by the fact that one needs to test a large number of composite null hypotheses across the whole epigenome. Two popular tests, the Wald-type Sobel's test and the joint significant test using the traditional null distribution are underpowered and thus can miss important scientific discoveries. In this article, we show that the null distribution of Sobel's test is not the standard normal distribution and the null distribution of the joint significant test is not uniform under the composite null of no mediation effect, especially in finite samples and under the singular point null case that the exposure has no effect on the mediator and the mediator has no effect on the outcome. Our results explain why these two tests are underpowered, and more importantly motivate us to develop a more powerful divide-aggregate composite-null test (DACT) for the composite null hypothesis of no mediation effect by leveraging epigenome-wide data. We adopted Efron's empirical null framework for assessing statistical significance of the DACT test. We showed analytically that the proposed DACT method had improved power, and could well control Type I error rate. Our extensive simulation studies showed that, in finite samples, the DACT method properly controlled the Type I error rate and outperformed Sobel's test and the joint significance test for detecting mediation effects. We applied the DACT method to the U.S. Department of Veterans Affairs Normative Aging Study, an ongoing prospective cohort study which included men who were aged 21 to 80 years at entry. We identified multiple DNA methylation CpG sites that might mediate the effect of smoking on lung function with effect sizes ranging from –0.18 to –0.79 and false discovery rate controlled at the level 0.05, including the CpG sites in the genes AHRR and F2RL3. Our sensitivity analysis found small residual correlations (less than 0.01) of the error terms between the outcome and mediator regressions, suggesting that our results are robust to unmeasured confounding factors. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

40. A general framework for functionally informed set-based analysis: Application to a large-scale colorectal cancer study

Author

Dong, Xinyuan, primary, Su, Yu-Ru, additional, Barfield, Richard, additional, Bien, Stephanie A., additional, He, Qianchuan, additional, Harrison, Tabitha A., additional, Huyghe, Jeroen R., additional, Keku, Temitope O., additional, Lindor, Noralane M., additional, Schafmayer, Clemens, additional, Chan, Andrew T., additional, Gruber, Stephen B., additional, Jenkins, Mark A., additional, Kooperberg, Charles, additional, Peters, Ulrike, additional, and Hsu, Li, additional

Published
2020
Full Text
View/download PDF

41. Genetic architectures of proximal and distal colorectal cancer are partly distinct

Author

Huyghe, Jeroen R, primary, Harrison, Tabitha A, additional, Bien, Stephanie A, additional, Hampel, Heather, additional, Figueiredo, Jane C, additional, Schmit, Stephanie L, additional, Conti, David V, additional, Chen, Sai, additional, Qu, Conghui, additional, Lin, Yi, additional, Barfield, Richard, additional, Baron, John A, additional, Cross, Amanda J, additional, Diergaarde, Brenda, additional, Duggan, David, additional, Harlid, Sophia, additional, Imaz, Liher, additional, Kang, Hyun Min, additional, Levine, David M, additional, Perduca, Vittorio, additional, Perez-Cornago, Aurora, additional, Sakoda, Lori C, additional, Schumacher, Fredrick R, additional, Slattery, Martha L, additional, Toland, Amanda E, additional, van Duijnhoven, Franzel JB, additional, Van Guelpen, Bethany, additional, Arndt, Volker, additional, Agudo, Antonio, additional, Albanes, Demetrius, additional, Alonso, M Henar, additional, Anderson, Kristin, additional, Arnau-Collell, Coral, additional, Banbury, Barbara, additional, Bassik, Michael C, additional, Berndt, Sonja I, additional, Bézieau, Stéphane, additional, Bishop, D Timothy, additional, Boehm, Juergen, additional, Boeing, Heiner, additional, Boutron-Ruault, Marie-Christine, additional, Brenner, Hermann, additional, Brezina, Stefanie, additional, Buch, Stephan, additional, Buchanan, Daniel D, additional, Burnett-Hartman, Andrea, additional, Caan, Bette J, additional, Campbell, Peter T, additional, Carr, Prudence, additional, Castells, Antoni, additional, Castellví-Bel, Sergi, additional, Chan, Andrew T, additional, Chang-Claude, Jenny, additional, Chanock, Stephen J, additional, Curtis, Keith R, additional, de la Chapelle, Albert, additional, Easton, Douglas F, additional, English, Dallas R, additional, Feskens, Edith JM, additional, Gala, Manish, additional, Gallinger, Steven J, additional, Gauderman, W James, additional, Giles, Graham G, additional, Goodman, Phyllis J, additional, Grady, William M, additional, Grove, John S, additional, Gsur, Andrea, additional, Gunter, Marc J, additional, Haile, Robert W, additional, Hampe, Jochen, additional, Hoffmeister, Michael, additional, Hopper, John L, additional, Hsu, Wan-Ling, additional, Huang, Wen-Yi, additional, Hudson, Thomas J, additional, Jenab, Mazda, additional, Jenkins, Mark A, additional, Joshi, Amit D, additional, Keku, Temitope O, additional, Kooperberg, Charles, additional, Kuhn, Tilman, additional, Küry, Sébastien, additional, Le Marchand, Loic, additional, Lejbkowicz, Flavio, additional, Li, Christopher I, additional, Li, Li, additional, Lieb, Wolfgang, additional, Lindblom, Annika, additional, Lindor, Noralane M, additional, Männistö, Satu, additional, Markowitz, Sanford D, additional, Milne, Roger L, additional, Moreno, Lorena, additional, Murphy, Neil, additional, Nassir, Rami, additional, Offit, Kenneth, additional, Ogino, Shuji, additional, Panico, Salvatore, additional, Parfrey, Patrick S, additional, Pearlman, Rachel, additional, Pharoah, Paul D P, additional, Phipps, Amanda I, additional, Platz, Elizabeth A, additional, Potter, John D, additional, Prentice, Ross L, additional, Qi, Lihong, additional, Raskin, Leon, additional, Rennert, Gad, additional, Rennert, Hedy S, additional, Riboli, Elio, additional, Schafmayer, Clemens, additional, Schoen, Robert E, additional, Seminara, Daniela, additional, Song, Mingyang, additional, Su, Yu-Ru, additional, Tangen, Catherine M, additional, Thibodeau, Stephen N, additional, Thomas, Duncan C, additional, Trichopoulou, Antonia, additional, Ulrich, Cornelia M, additional, Visvanathan, Kala, additional, Vodicka, Pavel, additional, Vodickova, Ludmila, additional, Vymetalkova, Veronika, additional, Weigl, Korbinian, additional, Weinstein, Stephanie J, additional, White, Emily, additional, Wolk, Alicja, additional, Woods, Michael O, additional, Wu, Anna H, additional, Abecasis, Goncalo R, additional, Nickerson, Deborah A, additional, Scacheri, Peter C, additional, Kundaje, Anshul, additional, Casey, Graham, additional, Gruber, Stephen B, additional, Hsu, Li, additional, Moreno, Victor, additional, Hayes, Richard B, additional, Newcomb, Polly A, additional, and Peters, Ulrike, additional

Published
2020
Full Text
View/download PDF

43. Reduced plasmablast frequency is associated with seronegative myasthenia gravis.

Author

Guptill, Jeffrey T., Barfield, Richard, Chan, Cliburn, Russo, Melissa A., Emmett, Doug, Raja, Shruti, Massey, Janice M., Juel, Vern C., Hobson‐Webb, Lisa D., Gable, Karissa L., Gonzalez, Natalia, Hammett, Alex, Howard, James F., Chopra, Manisha, Kaminski, Henry J., Siddiqi, Zaeem A., Migdal, Mattingly, and Yi, John S.

Abstract

Background: The immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG. Methods: We performed high‐dimensional flow cytometry on blood samples from SN MG patients (N = 68), healthy controls (N = 46), and acetylcholine receptor antibody (AChR+) MG patients (N = 27). We compared 12 immune cell subsets in SN MG to controls using logistic modeling via a discovery‐replication design. An exploratory analysis fit a multinomial model comparing AChR+ MG and controls to SN MG. Results: An increase in CD19+CD20−CD38hi plasmablast frequencies was associated with lower odds of being a SN MG case in both the discovery and replication analyses (discovery P‐value =.0003, replication P‐value =.0021). Interleukin (IL) ‐21 producing helper T cell frequencies were associated with a diagnosis of AChR+ MG (P =.004). Conclusions: Reduced plasmablast frequencies are strongly associated with a SN MG diagnosis and may be a useful diagnostic biomarker in the future. See Editorial on pages 439–441 in this issue. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

44. Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans: an epigenome-wide study in the NAS and KORA cohorts

Author

Carmona, Juan Jose, primary, Barfield, Richard T., additional, Panni, Tommaso, additional, Nwanaji-Enwerem, Jamaji C., additional, Just, Allan C., additional, Hutchinson, John N., additional, Colicino, Elena, additional, Karrasch, Stefan, additional, Wahl, Simone, additional, Kunze, Sonja, additional, Jafari, Nadereh, additional, Zheng, Yinan, additional, Hou, Lifang, additional, DeMeo, Dawn L., additional, Litonjua, Augusto A., additional, Vokonas, Pantel S., additional, Peters, Annette, additional, Lin, Xihong, additional, Schwartz, Joel, additional, Schulz, Holger, additional, and Baccarelli, Andrea A., additional

Published
2018
Full Text
View/download PDF

45. Epigenome-wide association analysis of daytime sleepiness in the Multi-Ethnic Study of Atherosclerosis reveals African-American specific associations

Author

Barfield, Richard, primary, Wang, Heming, additional, Liu, Yongmei, additional, Brody, Jennifer A, additional, Swenson, Brenton, additional, Li, Ruitong, additional, Bartz, Traci M., additional, Sotoodehnia, Nona, additional, Chen, Yii-der I., additional, Cade, Brian E., additional, Chen, Han, additional, Patel, Sanjay R., additional, Zhu, Xiaofeng, additional, Gharib, Sina A., additional, Johnson, W. Craig, additional, Rotter, Jerome I., additional, Saxena, Richa, additional, Purcell, Shaun, additional, Lin, Xihong, additional, Redline, Susan, additional, and Sofer, Tamar, additional

Published
2018
Full Text
View/download PDF

46. Trends in Planned Early Retirement

Author

Barfield, Richard E. and Morgan, James N.

Abstract

A national personal interview survey, repeating the core questions asked 10 years earlier on retirement plans, finds the previously recorded "age effect" to be apparently neither an age nor a cohort effect. Indeed, the new data point toward a "period of history" effect dominating changes in plans to retire early. (Author)

Published
1978

47. Trends in Satisfaction with Retirement

Author

Barfield, Richard E. and Morgan, James N.

Abstract

A national personal interview survey, repeating some questions asked eight-10 years earlier on post-retirement experiences, finds current retirees somewhat less satisfied with life after retirement than ones interviewed in the 1960s. Dissatisfaction with retirement experience continues to be associated with health problems and to some extent low income. (Author)

Published
1978

Catalog

Books, media, physical & digital resources
See catalog results