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2. Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident

Author

Morton, Lindsay M., Lee, Olivia W., Karyadi, Danielle M., Bogdanova, Tetiana I., Stewart, Chip, Hartley, Stephen W., Breeze, Charles E., Schonfeld, Sara J., Cahoon, Elizabeth K., Drozdovitch, Vladimir, Masiuk, Sergii, Chepurny, Mykola, Zurnadzhy, Liudmyla Yu, Dai, Jieqiong, Krznaric, Marko, Yeager, Meredith, Hutchinson, Amy, Hicks, Belynda D., Dagnall, Casey L., Steinberg, Mia K., Jones, Kristine, Jain, Komal, Jordan, Ben, Machiela, Mitchell J., Dawson, Eric T., Vij, Vibha, Gastier-Foster, Julie M., Bowen, Jay, Mabuchi, Kiyohiko, Hatch, Maureen, Berrington de Gonzalez, Amy, Getz, Gad, Tronko, Mykola D., Thomas, Gerry A., and Chanock, Stephen J.

Published
2024
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5. Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas

Author

Hughes, Odessica, Bentley, Amy R, Breeze, Charles E, Aguet, Francois, Xu, Xiaoguang, Nadkarni, Girish, Sun, Quan, Lin, Bridget M, Gilliland, Thomas, Meyer, Mariah C, Du, Jiawen, Raffield, Laura M, Kramer, Holly, Morton, Robert W, Gouveia, Mateus H, Atkinson, Elizabeth G, Valladares-Salgado, Adan, Wacher-Rodarte, Niels, Dueker, Nicole D, Guo, Xiuqing, Hai, Yang, Adeyemo, Adebowale, Best, Lyle G, Cai, Jianwen, Chen, Guanjie, Chong, Michael, Doumatey, Ayo, Eales, James, Goodarzi, Mark O, Ipp, Eli, Irvin, Marguerite Ryan, Jiang, Minzhi, Jones, Alana C, Kooperberg, Charles, Krieger, Jose E, Lange, Ethan M, Lanktree, Matthew B, Lash, James P, Lotufo, Paulo A, Loos, Ruth JF, My, Vy Thi Ha, Peralta-Romero, Jesús, Qi, Lihong, Raffel, Leslie J, Rich, Stephen S, Rodriquez, Erik J, Tarazona-Santos, Eduardo, Taylor, Kent D, Umans, Jason G, Wen, Jia, Young, Bessie A, Yu, Zhi, Zhang, Ying, Chen, Yii-Der Ida, Rundek, Tanja, Rotter, Jerome I, Cruz, Miguel, Fornage, Myriam, Lima-Costa, Maria Fernanda, Pereira, Alexandre C, Paré, Guillaume, Natarajan, Pradeep, Cole, Shelley A, Carson, April P, Lange, Leslie A, Li, Yun, Perez-Stable, Eliseo J, Do, Ron, Charchar, Fadi J, Tomaszewski, Maciej, Mychaleckyj, Josyf C, Rotimi, Charles, Morris, Andrew P, and Franceschini, Nora

Subjects
Biological Sciences, Genetics, Kidney Disease, Health Disparities, Human Genome, Renal and urogenital, Good Health and Well Being, Humans, Genome-Wide Association Study, Renal Insufficiency, Chronic, Glomerular Filtration Rate, Multifactorial Inheritance, Kidney, admixed populations, chronic kidney disease, eGFR, expression quantitative trait locus, fine-mapping, genome-wide association study, kidney function, multi-ancestry, polygenic scores
Abstract

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

Published
2024

6. Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits

Author

Peng, Qianqian, Liu, Xinxuan, Li, Wenran, Jing, Han, Li, Jiarui, Gao, Xingjian, Luo, Qi, Breeze, Charles E., Pan, Siyu, Zheng, Qiwen, Li, Guochao, Qian, Jiaqiang, Yuan, Liyun, Yuan, Na, You, Chenglong, Du, Siyuan, Zheng, Yuanting, Yuan, Ziyu, Tan, Jingze, Jia, Peilin, Wang, Jiucun, Zhang, Guoqing, Lu, Xianping, Shi, Leming, Guo, Shicheng, Liu, Yun, Ni, Ting, Wen, Bo, Zeng, Changqing, Jin, Li, Teschendorff, Andrew E., Liu, Fan, and Wang, Sijia

Published
2024
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7. A mammalian methylation array for profiling methylation levels at conserved sequences

Author

Arneson, Adriana, Haghani, Amin, Thompson, Michael J, Pellegrini, Matteo, Kwon, Soo Bin, Vu, Ha, Maciejewski, Emily, Yao, Mingjia, Li, Caesar Z, Lu, Ake T, Morselli, Marco, Rubbi, Liudmilla, Barnes, Bret, Hansen, Kasper D, Zhou, Wanding, Breeze, Charles E, Ernst, Jason, and Horvath, Steve

Subjects
Genetics, Human Genome, Animals, Biomarkers, Conserved Sequence, CpG Islands, DNA Methylation, Epigenesis, Genetic, Humans, Mammals, Mice, Mutation, Protein Processing, Post-Translational, Rats, Transcriptome
Abstract

Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures up to 36k CpGs per species that are well conserved across many mammalian species. We designed a set of probes that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development of epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others.

Published
2022

8. Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci

Author

Breeze, Charles E, Batorsky, Anna, Lee, Mi Kyeong, Szeto, Mindy D, Xu, Xiaoguang, McCartney, Daniel L, Jiang, Rong, Patki, Amit, Kramer, Holly J, Eales, James M, Raffield, Laura, Lange, Leslie, Lange, Ethan, Durda, Peter, Liu, Yongmei, Tracy, Russ P, Van Den Berg, David, Evans, Kathryn L, Kraus, William E, Shah, Svati, Tiwari, Hermant K, Hou, Lifang, Whitsel, Eric A, Jiang, Xiao, Charchar, Fadi J, Baccarelli, Andrea A, Rich, Stephen S, Morris, Andrew P, Irvin, Marguerite R, Arnett, Donna K, Hauser, Elizabeth R, Rotter, Jerome I, Correa, Adolfo, Hayward, Caroline, Horvath, Steve, Marioni, Riccardo E, Tomaszewski, Maciej, Beck, Stephan, Berndt, Sonja I, London, Stephanie J, Mychaleckyj, Josyf C, and Franceschini, Nora

Subjects
Biological Sciences, Genetics, Kidney Disease, Biotechnology, Health Disparities, Human Genome, Minority Health, 2.1 Biological and endogenous factors, Renal and urogenital, CpG Islands, DNA Methylation, Epigenesis, Genetic, Epigenomics, Gene Expression Regulation, Genetic Variation, Genetics, Population, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Kidney Function Tests, Phenotype, Quantitative Trait Loci, Quantitative Trait, Heritable, Racial Groups, Epigenetic, Kidney function, Gene regulation, Kidney development, DNA methylation, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed MESA Multi-Omics Working Group, Clinical Sciences
Abstract

BackgroundDNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach.MethodsThe study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses.ResultsWe identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development.ConclusionsWe uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.

Published
2021

9. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Heijmans, Bastiaan, ’t Hoen, Peter, van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret, Pool, René, van Dongen, Jenny, Hottenga, Jouke, van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje, Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Veldink, Jan, van den Berg, Leonard, van Duijn, Cornelia, Hofman, Bert, Isaacs, Aaron, Uitterlinden, André, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha, van ‘t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon, Swertz, Morris, van Zwet, Erik, Hoang, Thanh T., Lee, Yunsung, McCartney, Daniel L., Kersten, Elin T.G., Page, Christian M., Hulls, Paige M., Lee, Mikyeong, Walker, Rosie M., Breeze, Charles E., Bennett, Brian D., Burkholder, Adam B., Ward, James, Brantsæter, Anne Lise, Caspersen, Ida H., Motsinger-Reif, Alison A., Richards, Marie, White, Julie D., Zhao, Shanshan, Richmond, Rebecca C., Magnus, Maria C., Koppelman, Gerard H., Evans, Kathryn L., Marioni, Riccardo E., Håberg, Siri E., and London, Stephanie J.

Published
2024
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10. Epigenetic clock and methylation studies in the rhesus macaque

Author

Horvath, Steve, Zoller, Joseph A, Haghani, Amin, Jasinska, Anna J, Raj, Ken, Breeze, Charles E, Ernst, Jason, Vaughan, Kelli L, and Mattison, Julie A

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Aging, Human Genome, Animals, Chlorocebus aethiops, DNA Methylation, Epigenesis, Genetic, Epigenomics, Macaca mulatta, Promoter Regions, Genetic, Epigenetic clock, DNA methylation, Rhesus monkey, Nonhuman primate, Clinical sciences
Abstract

Methylation levels at specific CpG positions in the genome have been used to develop accurate estimators of chronological age in humans, mice, and other species. Although epigenetic clocks are generally species-specific, the principles underpinning them appear to be conserved at least across the mammalian class. This is exemplified by the successful development of epigenetic clocks for mice and several other mammalian species. Here, we describe epigenetic clocks for the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate in biological research. Using a custom methylation array (HorvathMammalMethylChip40), we profiled n = 281 tissue samples (blood, skin, adipose, kidney, liver, lung, muscle, and cerebral cortex). From these data, we generated five epigenetic clocks for macaques. These clocks differ with regard to applicability to different tissue types (pan-tissue, blood, skin), species (macaque only or both humans and macaques), and measure of age (chronological age versus relative age). Additionally, the age-based human-macaque clock exhibits a high age correlation (R = 0.89) with the vervet monkey (Chlorocebus sabaeus), another Old World species. Four CpGs within the KLF14 promoter were consistently altered with age in four tissues (adipose, blood, cerebral cortex, skin). Future studies will be needed to evaluate whether these epigenetic clocks predict age-related conditions in the rhesus macaque.

Published
2021

11. Whole genome sequence analyses of eGFR in 23,732 people representing multiple ancestries in the NHLBI trans-omics for precision medicine (TOPMed) consortium

Author

Lin, Bridget M, Grinde, Kelsey E, Brody, Jennifer A, Breeze, Charles E, Raffield, Laura M, Mychaleckyj, Josyf C, Thornton, Timothy A, Perry, James A, Baier, Leslie J, de las Fuentes, Lisa, Guo, Xiuqing, Heavner, Benjamin D, Hanson, Robert L, Hung, Yi-Jen, Qian, Huijun, Hsiung, Chao A, Hwang, Shih-Jen, Irvin, Margaret R, Jain, Deepti, Kelly, Tanika N, Kobes, Sayuko, Lange, Leslie, Lash, James P, Li, Yun, Liu, Xiaoming, Mi, Xuenan, Musani, Solomon K, Papanicolaou, George J, Parsa, Afshin, Reiner, Alex P, Salimi, Shabnam, Sheu, Wayne H-H, Shuldiner, Alan R, Taylor, Kent D, Smith, Albert V, Smith, Jennifer A, Tin, Adrienne, Vaidya, Dhananjay, Wallace, Robert B, Yamamoto, Kenichi, Sakaue, Saori, Matsuda, Koichi, Kamatani, Yoichiro, Momozawa, Yukihide, Yanek, Lisa R, Young, Betsi A, Zhao, Wei, Okada, Yukinori, Abecasis, Gonzalo, Psaty, Bruce M, Arnett, Donna K, Boerwinkle, Eric, Cai, Jianwen, Chen, Ida Yii-Der, Correa, Adolfo, Cupples, L Adrienne, He, Jiang, Kardia, Sharon LR, Kooperberg, Charles, Mathias, Rasika A, Mitchell, Braxton D, Nickerson, Deborah A, Turner, Steve T, Ramachandran, Vasan S, Rotter, Jerome I, Levy, Daniel, Kramer, Holly J, Köttgen, Anna, Consortium, NHLBI Trans-Omics for Precision Medicine, Group, TOPMed Kidney Working, Rich, Stephen S, Lin, Dan-Yu, Browning, Sharon R, and Franceschini, Nora

Subjects
Epidemiology, Health Sciences, Biotechnology, Human Genome, Genetics, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Alleles, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Glomerular Filtration Rate, Humans, Male, National Heart, Lung, and Blood Institute (U.S.), Polymorphism, Single Nucleotide, Precision Medicine, Public Health Surveillance, Quantitative Trait, Heritable, United States, Whole Genome Sequencing, Whole genome sequencing, Kidney traits, Rare variants, Ancestry-specific variants, Clinical Sciences, Public Health and Health Services, Clinical sciences
Abstract

BackgroundGenetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants.MethodsWe combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity.FindingsWhen testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10-11; METTL8, rs116951054, MAF 0.09%, P = 4.5 × 10-9; and MATK, rs539182790, MAF 0.05%, P = 3.4 × 10-9). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P = 1.2 × 10-9, nearest gene GATM, and rs71147340, MAF=0.34, P = 3.3 × 10-9, CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants.InterpretationThis study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.

Published
2021

14. Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning.

Author

van Dongen, Jenny and Breeze, Charles E.

Subjects
MONOZYGOTIC twins, DNA methylation, METHYLATION, EPIGENOMICS, GENETICS
Abstract

Background/Objectives: Human identical twins are born at a rate of 3–4 per 1000 live births. Many other mammals also occasionally produce monozygotic twins, referred to as sporadic polyembryony. The underlying mechanisms are unknown. Through epigenome-wide association studies (EWAS), we identified a robust DNA methylation signature in somatic tissues from human monozygotic (MZ) twins, comprising 834 differentially methylated positions (MZ-DMPs). The results point to a connection between monozygotic twinning and early genome programming and enable new angles to study monozygotic twinning. Methods: The mammalian methylation array (MMA) measures 38,608 CpGs focusing on regions that are well-conserved across many mammalian species, allowing for pan-mammalian comparative epigenomic studies. Here, we successfully map human MZ-DMPs to probes of the mammalian methylation array across 157 mammalian genomes. Results: As expected, based on the modest probe overlap between Illumina 450k/EPIC and mammalian methylation array probes, only a subset of MZ-DMPs reside in conserved regions covered by the mammalian methylation array. These include probes mapping to NPAS3, KLHL35, CASZ1, and ATP2B2. Re-analysis restricting the original EWAS in humans to conserved MMA regions yielded additional MZ-DMPs, suggesting that more loci may be detected by application of the mammalian array to monozygotic twins. Conclusions: In conclusion, the mammalian methylation array may prove to be a promising platform to study whether a shared DNA methylation signature of sporadic polyembryony exists across diverse mammalian species. This may potentially point to shared underlying mechanisms. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Author Correction: DNA methylation predicts age and provides insight into exceptional longevity of bats

Author

Wilkinson, Gerald S., Adams, Danielle M., Haghani, Amin, Lu, Ake T., Zoller, Joseph, Breeze, Charles E., Arnold, Bryan D., Ball, Hope C., Carter, Gerald G., Cooper, Lisa Noelle, Dechmann, Dina K. N., Devanna, Paolo, Fasel, Nicolas J., Galazyuk, Alexander V., Günther, Linus, Hurme, Edward, Jones, Gareth, Knörnschild, Mirjam, Lattenkamp, Ella Z., Li, Caesar Z., Mayer, Frieder, Reinhardt, Josephine A., Medellin, Rodrigo A., Nagy, Martina, Pope, Brian, Power, Megan L., Ransome, Roger D., Teeling, Emma C., Vernes, Sonja C., Zamora-Mejías, Daniel, Zhang, Joshua, Faure, Paul A., Greville, Lucas J., Herrera M., L. Gerardo, Flores-Martínez, José J., and Horvath, Steve

Published
2022
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21. Epigenetics of complex traits and diseases

Author

Breeze, Charles E.

Subjects
616.99
Abstract

Thousands of genetic and epigenetic variants have been identified for many common diseases including cancer through genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS). To advance the complex interpretation of both GWAS and EWAS results, I developed new software tools (FORGE2 and eFORGE) for the analysis and interpretation of GWAS and EWAS data, respectively. Both tools determine the cell type-specific regulatory component of a set of target regions (either GWAS-identified genetic variants or EWAS-identified differentially methylated positions). This is achieved by detecting enrichment of overlap with histone mark peaks or DNase I hypersensitive sites across hundreds of tissues, primary cell types, and cell lines from the ENCODE, Roadmap Epigenomics, and BLUEPRINT projects. Application of both tools to publicly available datasets identified novel disease-relevant cell types for many common diseases, a stem cell-like signature in cancer EWAS, and also demonstrated the ability to detect cell-composition effects for EWAS performed on heterogeneous tissues. To complement these bioinformatics efforts and validate selected variants predicted by FORGE2, eFORGE and additional analyses, I performed conformation capture using 4C-seq to fine-map the 3D context of the genomic regions involved, uncovering novel interactions for autoimmunity-associated variants and IKZF3.

Published
2017

22. Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China.

Author

Rahman, Mohammad L., Breeze, Charles E., Xiao-Ou Shu, Wong, Jason Y. Y., Blechter, Batel, Cardenas, Andres, Wang, Xuting, Bu-Tian Ji, Wei Hu, Qiuyin Cai, Hosgood, H. Dean, Gong Yang, Jianxin Shi, Jirong Long, Yu-Tang Gao, Bell, Douglas A., Wei Zheng, Rothman, Nathaniel, and Qing Lan

Subjects
INDOOR air pollution, CONNECTIVE tissue cells, REGULATORY T cells, LEFT heart ventricle, EPIDERMAL growth factor receptors, HEAD & neck cancer
Published
2024
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23. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Hoang, Thanh T., primary, Lee, Yunsung, additional, McCartney, Daniel L., additional, Kersten, Elin T.G., additional, Page, Christian M., additional, Hulls, Paige M., additional, Lee, Mikyeong, additional, Walker, Rosie M., additional, Breeze, Charles E., additional, Bennett, Brian D., additional, Burkholder, Adam B., additional, Ward, James, additional, Brantsæter, Anne Lise, additional, Caspersen, Ida H., additional, Motsinger-Reif, Alison A., additional, Richards, Marie, additional, White, Julie D., additional, Zhao, Shanshan, additional, Richmond, Rebecca C., additional, Magnus, Maria C., additional, Koppelman, Gerard H., additional, Evans, Kathryn L., additional, Marioni, Riccardo E., additional, Håberg, Siri E., additional, London, Stephanie J., additional, Heijmans, Bastiaan, additional, ’t Hoen, Peter, additional, van Meurs, Joyce, additional, Jansen, Rick, additional, Franke, Lude, additional, Boomsma, Dorret, additional, Pool, René, additional, van Dongen, Jenny, additional, Hottenga, Jouke, additional, van Greevenbroek, Marleen, additional, Stehouwer, Coen, additional, van der Kallen, Carla, additional, Schalkwijk, Casper, additional, Wijmenga, Cisca, additional, Zhernakova, Sasha, additional, Tigchelaar, Ettje, additional, Slagboom, P. Eline, additional, Beekman, Marian, additional, Deelen, Joris, additional, Van Heemst, Diana, additional, Veldink, Jan, additional, van den Berg, Leonard, additional, van Duijn, Cornelia, additional, Hofman, Bert, additional, Isaacs, Aaron, additional, Uitterlinden, André, additional, Jhamai, P. Mila, additional, Verbiest, Michael, additional, Suchiman, H. Eka, additional, Verkerk, Marijn, additional, van der Breggen, Ruud, additional, van Rooij, Jeroen, additional, Lakenberg, Nico, additional, Mei, Hailiang, additional, van Iterson, Maarten, additional, van Galen, Michiel, additional, Bot, Jan, additional, Zhernakova, Dasha, additional, van ‘t Hof, Peter, additional, Deelen, Patrick, additional, Nooren, Irene, additional, Moed, Matthijs, additional, Vermaat, Martijn, additional, Luijk, René, additional, Bonder, Marc, additional, van Dijk, Freerk, additional, Arindrarto, Wibowo, additional, Kielbasa, Szymon, additional, Swertz, Morris, additional, and van Zwet, Erik, additional

Published
2024
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24. Identical twins carry a persistent epigenetic signature of early genome programming

Author

van Dongen, Jenny, Gordon, Scott D., McRae, Allan F., Odintsova, Veronika V., Mbarek, Hamdi, Breeze, Charles E., Sugden, Karen, Lundgren, Sara, Castillo-Fernandez, Juan E., Hannon, Eilis, Moffitt, Terrie E., Hagenbeek, Fiona A., van Beijsterveldt, Catharina E. M., Jan Hottenga, Jouke, Tsai, Pei-Chien, Min, Josine L., Hemani, Gibran, Ehli, Erik A., Paul, Franziska, Stern, Claudio D., Heijmans, Bastiaan T., Slagboom, P. Eline, Daxinger, Lucia, van der Maarel, Silvère M., de Geus, Eco J. C., Willemsen, Gonneke, Montgomery, Grant W., Reversade, Bruno, Ollikainen, Miina, Kaprio, Jaakko, Spector, Tim D., Bell, Jordana T., Mill, Jonathan, Caspi, Avshalom, Martin, Nicholas G., and Boomsma, Dorret I.

Published
2021
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25. DNA methylation predicts age and provides insight into exceptional longevity of bats

Author

Wilkinson, Gerald S., Adams, Danielle M., Haghani, Amin, Lu, Ake T., Zoller, Joseph, Breeze, Charles E., Arnold, Bryan D., Ball, Hope C., Carter, Gerald G., Cooper, Lisa Noelle, Dechmann, Dina K. N., Devanna, Paolo, Fasel, Nicolas J., Galazyuk, Alexander V., Günther, Linus, Hurme, Edward, Jones, Gareth, Knörnschild, Mirjam, Lattenkamp, Ella Z., Li, Caesar Z., Mayer, Frieder, Reinhardt, Josephine A., Medellin, Rodrigo A., Nagy, Martina, Pope, Brian, Power, Megan L., Ransome, Roger D., Teeling, Emma C., Vernes, Sonja C., Zamora-Mejías, Daniel, Zhang, Joshua, Faure, Paul A., Greville, Lucas J., Herrera M., L. Gerardo, Flores-Martínez, José J., and Horvath, Steve

Published
2021
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26. Author Correction: DNA methylation predicts age and provides insight into exceptional longevity of bats

Author

Wilkinson, Gerald S., Adams, Danielle M., Haghani, Amin, Lu, Ake T., Zoller, Joseph, Breeze, Charles E., Arnold, Bryan D., Ball, Hope C., Carter, Gerald G., Cooper, Lisa Noelle, Dechmann, Dina K. N., Devanna, Paolo, Fasel, Nicolas J., Galazyuk, Alexander V., Günther, Linus, Hurme, Edward, Jones, Gareth, Knörnschild, Mirjam, Lattenkamp, Ella Z., Li, Caesar Z., Mayer, Frieder, Reinhardt, Josephine A., Medellin, Rodrigo A., Nagy, Martina, Pope, Brian, Power, Megan L., Ransome, Roger D., Teeling, Emma C., Vernes, Sonja C., Zamora-Mejías, Daniel, Zhang, Joshua, Faure, Paul A., Greville, Lucas J., Horvath, Steve, Herrera M., L. Gerardo, and Flores-Martínez, José J.

Published
2021
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29. Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions

Author

Teixeira, Vitor H., Pipinikas, Christodoulos P., Pennycuick, Adam, Lee-Six, Henry, Chandrasekharan, Deepak, Beane, Jennifer, Morris, Tiffany J., Karpathakis, Anna, Feber, Andrew, Breeze, Charles E., Ntolios, Paschalis, Hynds, Robert E., Falzon, Mary, Capitanio, Arrigo, Carroll, Bernadette, Durrenberger, Pascal F., Hardavella, Georgia, Brown, James M., Lynch, Andy G., Farmery, Henry, Paul, Dirk S., Chambers, Rachel C., McGranahan, Nicholas, Navani, Neal, Thakrar, Ricky M., Swanton, Charles, Beck, Stephan, George, Phillip Jeremy, Spira, Avrum, Campbell, Peter J., Thirlwell, Christina, and Janes, Sam M.

Published
2019
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30. DNA methylation networks underlying mammalian traits

Author

Haghani, Amin, primary, Li, Caesar Z., additional, Robeck, Todd R., additional, Zhang, Joshua, additional, Lu, Ake T., additional, Ablaeva, Julia, additional, Acosta-Rodríguez, Victoria A., additional, Adams, Danielle M., additional, Alagaili, Abdulaziz N., additional, Almunia, Javier, additional, Aloysius, Ajoy, additional, Amor, Nabil M.S., additional, Ardehali, Reza, additional, Arneson, Adriana, additional, Baker, C. Scott, additional, Banks, Gareth, additional, Belov, Katherine, additional, Bennett, Nigel C., additional, Black, Peter, additional, Blumstein, Daniel T., additional, Bors, Eleanor K., additional, Breeze, Charles E., additional, Brooke, Robert T., additional, Brown, Janine L., additional, Carter, Gerald, additional, Caulton, Alex, additional, Cavin, Julie M., additional, Chakrabarti, Lisa, additional, Chatzistamou, Ioulia, additional, Chavez, Andreas S., additional, Chen, Hao, additional, Cheng, Kaiyang, additional, Chiavellini, Priscila, additional, Choi, Oi-Wa, additional, Clarke, Shannon, additional, Cook, Joseph A., additional, Cooper, Lisa N., additional, Cossette, Marie-Laurence, additional, Day, Joanna, additional, DeYoung, Joseph, additional, Dirocco, Stacy, additional, Dold, Christopher, additional, Dunnum, Jonathan L., additional, Ehmke, Erin E., additional, Emmons, Candice K., additional, Emmrich, Stephan, additional, Erbay, Ebru, additional, Erlacher-Reid, Claire, additional, Faulkes, Chris G., additional, Fei, Zhe, additional, Ferguson, Steven H., additional, Finno, Carrie J., additional, Flower, Jennifer E., additional, Gaillard, Jean-Michel, additional, Garde, Eva, additional, Gerber, Livia, additional, Gladyshev, Vadim N., additional, Goya, Rodolfo G., additional, Grant, Matthew J, additional, Green, Carla B., additional, Hanson, M. Bradley, additional, Hart, Daniel W., additional, Haulena, Martin, additional, Herrick, Kelsey, additional, Hogan, Andrew N., additional, Hogg, Carolyn J., additional, Hore, Timothy A., additional, Huang, Taosheng, additional, Izpisua Belmonte, Juan Carlos, additional, Jasinska, Anna J., additional, Jones, Gareth, additional, Jourdain, Eve, additional, Kashpur, Olga, additional, Katcher, Harold, additional, Katsumata, Etsuko, additional, Kaza, Vimala, additional, Kiaris, Hippokratis, additional, Kobor, Michael S., additional, Kordowitzki, Pawel, additional, Koski, William R., additional, Krützen, Michael, additional, Kwon, Soo Bin, additional, Larison, Brenda, additional, Lee, Sang-Goo, additional, Lehmann, Marianne, additional, Lemaître, Jean-François, additional, Levine, Andrew J., additional, Li, Xinmin, additional, Li, Cun, additional, Lim, Andrea R., additional, Lin, David T. S., additional, Lindemann, Dana M., additional, Liphardt, Schuyler W., additional, Little, Thomas J., additional, Macoretta, Nicholas, additional, Maddox, Dewey, additional, Matkin, Craig O., additional, Mattison, Julie A., additional, McClure, Matthew, additional, Mergl, June, additional, Meudt, Jennifer J., additional, Montano, Gisele A., additional, Mozhui, Khyobeni, additional, Munshi-South, Jason, additional, Murphy, William J., additional, Naderi, Asieh, additional, Nagy, Martina, additional, Narayan, Pritika, additional, Nathanielsz, Peter W., additional, Nguyen, Ngoc B., additional, Niehrs, Christof, additional, Nyamsuren, Batsaikhan, additional, O’Brien, Justine K., additional, Ginn, Perrie O’Tierney, additional, Odom, Duncan T, additional, Ophir, Alexander G., additional, Osborn, Steve, additional, Ostrander, Elaine A., additional, Parsons, Kim M., additional, Paul, Kimberly C., additional, Pedersen, Amy B., additional, Pellegrini, Matteo, additional, Peters, Katharina J., additional, Petersen, Jessica L., additional, Pietersen, Darren W., additional, Pinho, Gabriela M., additional, Plassais, Jocelyn, additional, Poganik, Jesse R., additional, Prado, Natalia A., additional, Reddy, Pradeep, additional, Rey, Benjamin, additional, Ritz, Beate R., additional, Robbins, Jooke, additional, Rodriguez, Magdalena, additional, Russell, Jennifer, additional, Rydkina, Elena, additional, Sailer, Lindsay L., additional, Salmon, Adam B., additional, Sanghavi, Akshay, additional, Schachtschneider, Kyle M., additional, Schmitt, Dennis, additional, Schmitt, Todd, additional, Schomacher, Lars, additional, Schook, Lawrence B., additional, Sears, Karen E., additional, Seifert, Ashley W., additional, Shafer, Aaron B.A., additional, Shindyapina, Anastasia V., additional, Simmons, Melanie, additional, Singh, Kavita, additional, Sinha, Ishani, additional, Slone, Jesse, additional, Snell, Russel G., additional, Soltanmohammadi, Elham, additional, Spangler, Matthew L., additional, Spriggs, Maria, additional, Staggs, Lydia, additional, Stedman, Nancy, additional, Steinman, Karen J., additional, Stewart, Donald T, additional, Sugrue, Victoria J., additional, Szladovits, Balazs, additional, Takahashi, Joseph S., additional, Takasugi, Masaki, additional, Teeling, Emma C., additional, Thompson, Michael J., additional, Van Bonn, Bill, additional, Vernes, Sonja C., additional, Villar, Diego, additional, Vinters, Harry V., additional, Vu, Ha, additional, Wallingford, Mary C., additional, Wang, Nan, additional, Wilkinson, Gerald S., additional, Williams, Robert W., additional, Yan, Qi, additional, Yao, Mingjia, additional, Young, Brent G., additional, Zhang, Bohan, additional, Zhang, Zhihui, additional, Zhao, Yang, additional, Zhao, Peng, additional, Zhou, Wanding, additional, Zoller, Joseph A., additional, Ernst, Jason, additional, Seluanov, Andrei, additional, Gorbunova, Vera, additional, Yang, X. William, additional, Raj, Ken, additional, and Horvath, Steve, additional

Published
2023
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33. Abstract 3483: Epigenome-wide association study of lung cancer among never-smokers in two prospective cohorts in Shanghai

Author

Rahman, Mohammad L., primary, Breeze, Charles E., additional, Shu, Xiao-Ou, additional, Wong, Jason YY, additional, Cardenas, Andres, additional, Wang, Xuting, additional, Ji, Bu-Tian, additional, Hu, Wei, additional, Blechter, Batel, additional, Cai, Qiuyin, additional, Hosgood, H Dean, additional, Yang, Gong, additional, Shi, Jianxin, additional, Long, Jirong, additional, Gao, Yu-Tang, additional, Bell, Douglas, additional, Zheng, Wei, additional, Lan, Qing, additional, and Rothman, Nathaniel, additional

Published
2023
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34. Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders

Author

Cilleros-Portet, Ariadna, primary, Lesseur, Corina, additional, Mari, Sergi, additional, Cosin-Tomas, Marta, additional, Lozano, Manuel, additional, Irizar, Amaia, additional, Burt, Amber, additional, Garcia-Santisteban, Iraia, additional, Garrido Martin, Diego, additional, Escaramis, Georgia, additional, Hernangomez-Laderas, Alba, additional, Soler-Blasco, Raquel, additional, Breeze, Charles E., additional, Gonzalez-Garcia, Barbara P., additional, Santa-Marina, Loreto, additional, Chen, Jia, additional, Llop, Sabrina, additional, Fernandez, Mariana F., additional, Vrijhed, Martine, additional, Ibarluzea, Jesus, additional, Guxens, Monica, additional, Marsit, Carmen, additional, Bustamante, Mariona, additional, Bilbao, Jose Ramon, additional, and Fernandez-Jimenez, Nora, additional

Published
2023
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35. Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders

Author

Cilleros-Portet, Ariadna, Lesseur, Corina, Marí, Sergi, Cosin-Tomas, Marta, Lozano, Manuel, Irizar, Amaia, Burt, Amber, García-Santisteban, Iraia, Martín, Diego Garrido, Escaramís, Geòrgia, Hernangomez-Laderas, Alba, Soler-Blasco, Raquel, Breeze, Charles E., Gonzalez-Garcia, Bárbara P., Santa-Marina, Loreto, Chen, Jia, Llop, Sabrina, Fernández, Mariana F., Vrijhed, Martine, Ibarluzea, Jesús, Guxens, Mònica, Marsit, Carmen, Bustamante, Mariona, Bilbao, Jose Ramon, and Fernandez-Jimenez, Nora

Subjects
Article
Abstract

Increasing evidence supports the role of placenta in neurodevelopment and potentially, in the later onset of neuropsychiatric disorders. Recently, methylation quantitative trait loci (mQTL) and interaction QTL (iQTL) maps have proven useful to understand SNP-genome wide association study (GWAS) relationships, otherwise missed by conventional expression QTLs. In this context, we propose that part of the genetic predisposition to complex neuropsychiatric disorders acts through placental DNA methylation (DNAm). We constructed the first public placentalcis-mQTL database including nearly eight million mQTLs calculated in 368 fetal placenta DNA samples from the INMA project, ran cell type- and gestational age-imQTL models and combined those data with the summary statistics of the largest GWAS on 10 neuropsychiatric disorders using Summary-based Mendelian Randomization (SMR) and colocalization. Finally, we evaluated the influence of the DNAm sites identified on placental gene expression in the RICHS cohort. We found that placentalcis-mQTLs are highly enriched in placenta-specific active chromatin regions, and useful to map the etiology of neuropsychiatric disorders at prenatal stages. Specifically, part of the genetic burden for schizophrenia, bipolar disorder and major depressive disorder confers risk through placental DNAm. The potential causality of several of the observed associations is reinforced by secondary association signals identified in conditional analyses, regional pleiotropic methylation signals associated to the same disorder, and cell type- imQTLs, additionally associated to the expression levels of relevant immune genes in placenta. In conclusion, the genetic risk of several neuropsychiatric disorders could operate, at least in part, through DNAm and associated gene expression in placenta.

Published
2023
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36. FORGEdb: systematic analysis of candidate causal variants to uncover target genes and mechanisms in complex traits

Author

Breeze, Charles E., primary, Haugen, Eric, additional, Gutierrez-Arcelus, María, additional, Yao, Xiaozheng, additional, Teschendorff, Andrew, additional, Beck, Stephan, additional, Dunham, Ian, additional, Stamatoyannopoulos, John, additional, Franceschini, Nora, additional, Machiela, Mitchell J., additional, and Berndt, Sonja I., additional

Published
2022
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38. Pulmonary Function and Blood DNA Methylation: A Multiancestry Epigenome-Wide Association Meta-analysis

Author

Lee, Mikyeong, primary, Huan, Tianxiao, additional, McCartney, Daniel L., additional, Chittoor, Geetha, additional, de Vries, Maaike, additional, Lahousse, Lies, additional, Nguyen, Jennifer N., additional, Brody, Jennifer A., additional, Castillo-Fernandez, Juan, additional, Terzikhan, Natalie, additional, Qi, Cancan, additional, Joehanes, Roby, additional, Min, Josine L., additional, Smilnak, Gordon J., additional, Shaw, Jessica R., additional, Yang, Chen Xi, additional, Colicino, Elena, additional, Hoang, Thanh T., additional, Bermingham, Mairead L., additional, Xu, Hanfei, additional, Justice, Anne E., additional, Xu, Cheng-Jian, additional, Rich, Stephen S., additional, Cox, Simon R., additional, Vonk, Judith M., additional, Prokić, Ivana, additional, Sotoodehnia, Nona, additional, Tsai, Pei-Chien, additional, Schwartz, Joel D., additional, Leung, Janice M., additional, Sikdar, Sinjini, additional, Walker, Rosie M., additional, Harris, Sarah E., additional, van der Plaat, Diana A., additional, Van Den Berg, David J., additional, Bartz, Traci M., additional, Spector, Tim D., additional, Vokonas, Pantel S., additional, Marioni, Riccardo E., additional, Taylor, Adele M., additional, Liu, Yongmei, additional, Barr, R. Graham, additional, Lange, Leslie A., additional, Baccarelli, Andrea A., additional, Obeidat, Ma’en, additional, Fornage, Myriam, additional, Wang, Tianyuan, additional, Ward, James M., additional, Motsinger-Reif, Alison A., additional, Hemani, Gibran, additional, Koppelman, Gerard H., additional, Bell, Jordana T., additional, Gharib, Sina A., additional, Brusselle, Guy, additional, Boezen, H. Marike, additional, North, Kari E., additional, Levy, Daniel, additional, Evans, Kathryn L., additional, Dupuis, Josée, additional, Breeze, Charles E., additional, Manichaikul, Ani, additional, and London, Stephanie J., additional

Published
2022
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39. Predictors of postoperative complications and readmissions in laparoscopic pancreas resection: Results of a cohort 105 consecutive. Cases. A retrospective study

Author

Cienfuegos, Javier A., primary, Hurtado-Pardo, Luis, additional, Breeze, Charles E., additional, Guillen, Francisco, additional, Valenti, Víctor, additional, Zozaya, Gabriel, additional, Martí, Pablo, additional, Benito, Alberto, additional, Pardo, Fernando, additional, Hernández Lizoáin, José Luis, additional, and Rotellar, Fernando, additional

Published
2022
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41. Author Correction:DNA methylation predicts age and provides insight into exceptional longevity of bats (Nature Communications, (2021), 12, 1, (1615), 10.1038/s41467-021-21900-2)

Author

Wilkinson, Gerald S., Adams, Danielle M., Haghani, Amin, Lu, Ake T., Zoller, Joseph, Breeze, Charles E., Arnold, Bryan D., Ball, Hope C., Carter, Gerald G., Cooper, Lisa Noelle, Dechmann, Dina K.N., Devanna, Paolo, Fasel, Nicolas J., Galazyuk, Alexander V., Günther, Linus, Hurme, Edward, Jones, Gareth, Knörnschild, Mirjam, Lattenkamp, Ella Z., Li, Caesar Z., Mayer, Frieder, Reinhardt, Josephine A., Medellin, Rodrigo A., Nagy, Martina, Pope, Brian, Power, Megan L., Ransome, Roger D., Teeling, Emma C., Vernes, Sonja C., Zamora-Mejías, Daniel, Zhang, Joshua, Faure, Paul A., Greville, Lucas J., Horvath, Steve, Herrera M, L. Gerardo, and Flores-Martínez, José J.

Published
2021
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42. Additional file 1 of Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci

Author

Breeze, Charles E., Batorsky, Anna, Lee, Mi Kyeong, Szeto, Mindy D., Xiaoguang Xu, McCartney, Daniel L., Jiang, Rong, Patki, Amit, Kramer, Holly J., Eales, James M., Raffield, Laura, Lange, Leslie, Lange, Ethan, Durda, Peter, Yongmei Liu, Tracy, Russ P., Van Den Berg, David, Evans, Kathryn L., Kraus, William E., Svati Shah, Hermant K. Tiwari, Lifang Hou, Whitsel, Eric A., Jiang, Xiao, Charchar, Fadi J., Baccarelli, Andrea A., Rich, Stephen S., Morris, Andrew P., Irvin, Marguerite R., Arnett, Donna K., Hauser, Elizabeth R., Rotter, Jerome I., Correa, Adolfo, Hayward, Caroline, Horvath, Steve, Marioni, Riccardo E., Tomaszewski, Maciej, Beck, Stephan, Berndt, Sonja I., London, Stephanie J., Josyf C. Mychaleckyj, and Franceschini, Nora

Abstract

Additional file 1: Supplementary Figures. Figure S1 to S7. Study design, QQ plots, Manhattan plots, forest plots and eFORGE/FORGE2 analyses.

Published
2021
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44. Epigenetic predictors of maximum lifespan and other life history traits in mammals

Author

Li, Caesar Z., primary, Haghani, Amin, additional, Robeck, Todd R., additional, Villar, Diego, additional, Lu, Ake T., additional, Zhang, Joshua, additional, Faulkes, Chris G., additional, Vu, Ha, additional, Ablaeva, Julia, additional, Adams, Danielle M., additional, Ardehali, Reza, additional, Arneson, Adriana, additional, Baker, C. Scott, additional, Belov, Katherine, additional, Blumstein, Daniel T., additional, Bors, Eleanor K., additional, Breeze, Charles E., additional, Brooke, Robert T., additional, Brown, Janine L., additional, Caulton, Alex, additional, Cavin, Julie M., additional, Chatzistamou, Ioulia, additional, Chen, Hao, additional, Chiavellini, Priscila, additional, Choi, Oi-Wa, additional, Clarke, Shannon, additional, DeYoung, Joseph, additional, Emmons, Candice K., additional, Emmrich, Stephan, additional, Fei, Zhe, additional, Ferguson, Steven H., additional, Finno, Carrie J., additional, Flower, Jennifer E., additional, Gaillard, Jean-Michel, additional, Garde, Eva, additional, Gladyshev, Vadim N., additional, Goya, Rodolfo G., additional, Hanson, M. Bradley, additional, Haulena, Martin, additional, Herrick, Kelsey, additional, Hogan, Andrew N., additional, Hogg, Carolyn J., additional, Hore, Timothy A., additional, Jasinska, Anna J., additional, Jones, Gareth, additional, Jourdain, Eve, additional, Kashpur, Olga, additional, Katcher, Harold, additional, Katsumata, Etsuko, additional, Kaza, Vimala, additional, Kiaris, Hippokratis, additional, Kobor, Michael S., additional, Kordowitzki, Pawel, additional, Koski, William R., additional, Larison, Brenda, additional, Lee, Sang-Goo, additional, Lehmann, Marianne, additional, Lemaitre, Jean-Francois, additional, Levine, Andrew J., additional, Li, Cun, additional, Li, Xinmin, additional, Lin, David TS, additional, Lindemann, Dana M., additional, Macoretta, Nicholas, additional, Maddox, Dewey, additional, Matkin, Craig O., additional, Mattison, Julie A., additional, Mergl, June, additional, Meudt, Jennifer J., additional, Montano, Gisele A., additional, Mozhui, Khyobeni, additional, Naderi, Asieh, additional, Nagy, Martina, additional, Narayan, Pritika, additional, Nathanielsz, Peter W., additional, Nguyen, Ngoc B., additional, Niehrs, Christof, additional, Odom, Duncan T, additional, Ophir, Alexander G., additional, Ostrander, Elaine A., additional, O'Tierney Ginn, Perrie, additional, Parsons, Kim M., additional, Paul, Kimberly C., additional, Pellegrini, Matteo, additional, Pinho, Gabriela M., additional, Plassais, Jocelyn, additional, Prado, Natalia A., additional, Rey, Benjamin, additional, Ritz, Beate R., additional, Robbins, Jooke, additional, Rodriguez, Magdalena, additional, Russell, Jennifer, additional, Rydkina, Elena, additional, Sailer, Lindsay L., additional, Salmon, Adam B., additional, Sanghavi, Akshay, additional, Schachtschneider, Kyle M., additional, Schmitt, Dennis, additional, Schomacher, Lars, additional, Schook, Lawrence B., additional, Sears, Karen E., additional, Seifert, Ashley W., additional, Shindyapina, Anastasia V., additional, Singh, Kavita, additional, Sinha, Ishani, additional, Snell, Russel G., additional, Soltanmohammadi, Elham, additional, Spangler, Matthew L., additional, Spriggs, Maria, additional, Steinman, Karen J., additional, Sugrue, Victoria J., additional, Szladovits, Balazs, additional, Takasugi, Masaki, additional, Teeling, Emma C., additional, Van Bonn, Bill, additional, Vernes, Sonja C., additional, Vinters, Harry V., additional, Wallingford, Mary C., additional, Wang, Nan, additional, Wilkinson, Gerald S., additional, Williams, Robert W., additional, Yang, X. William, additional, Young, Brent G., additional, Zhang, Bohan, additional, Zhang, Zhihui, additional, Zhao, Peng, additional, Zhao, Yang, additional, Zhou, Wanding, additional, Zoller, Joseph A., additional, Ernst, Jason, additional, Seluanov, Andrei, additional, Raj, Ken, additional, Gorbunova, Vera, additional, and Horvath, Steve, additional

Published
2021
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45. DNA methylation predicts age and provides insight into exceptional longevity of bats.

Author

Wilkinson, Gerald S., Adams, Danielle M., Haghani, Amin, Lu, Ake T., Zoller, Joseph, Breeze, Charles E., Arnold, Bryan D., Ball, Hope C., Carter, Gerald G., Cooper, Lisa Noelle, Dechmann, Dina K. N., Devanna, Paolo, Fasel, Nicolas J., Galazyuk, Alexander V., Günther, Linus, Hurme, Edward, Jones, Gareth, Knörnschild, Mirjam, Lattenkamp, Ella Z., and Li, Caesar Z.

Subjects
LONGEVITY, DNA methylation, AGE, BATS, PROMOTERS (Genetics), GENETIC transcription regulation
Abstract

Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression. DNA methylation profiles from 26 bat species accurately predicts chronological age, while longevity-related methylation patterns across the genome suggest that bat longevity results from augmented immune response and cancer suppression. [ABSTRACT FROM AUTHOR]

Published
2022
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46. Identical twins carry a persistent epigenetic signature of early genome programming

Author

Reversade, Bruno, van Dongen, Jenny; Gordon, Scott D.; McRae, Allan F.; Odintsova, Veronika V.; Mbarek, Hamdi; Breeze, Charles E.; Sugden, Karen; Lundgren, Sara; Castillo-Fernandez, Juan E.; Hannon, Eilis; Moffitt, Terrie E.; Hagenbeek, Fiona A.; van Beijsterveldt, Catharina E. M.; Hottenga, Jouke Jan; Tsai, Pei-Chien; Min, Josine L.; Hemani, Gibran; Ehli, Erik A.; Paul, Franziska; Stern, Claudio D.; Heijmans, Bastiaan T.; Slagboom, P. Eline; Daxinger, Lucia; van der Maarel, Silvere M.; de Geus, E. J. C.; Willemsen, Gonneke; Montgomery, Grant W.; Ollikainen, Miina; Kaprio, Jaakko; Spector, Tim D.; Bell, Jordana T.; Mill, Jonathan; Caspi, Avshalom; Martin, Nicholas G.; Boomsma, Dorret, I., School of Medicine, Reversade, Bruno, van Dongen, Jenny; Gordon, Scott D.; McRae, Allan F.; Odintsova, Veronika V.; Mbarek, Hamdi; Breeze, Charles E.; Sugden, Karen; Lundgren, Sara; Castillo-Fernandez, Juan E.; Hannon, Eilis; Moffitt, Terrie E.; Hagenbeek, Fiona A.; van Beijsterveldt, Catharina E. M.; Hottenga, Jouke Jan; Tsai, Pei-Chien; Min, Josine L.; Hemani, Gibran; Ehli, Erik A.; Paul, Franziska; Stern, Claudio D.; Heijmans, Bastiaan T.; Slagboom, P. Eline; Daxinger, Lucia; van der Maarel, Silvere M.; de Geus, E. J. C.; Willemsen, Gonneke; Montgomery, Grant W.; Ollikainen, Miina; Kaprio, Jaakko; Spector, Tim D.; Bell, Jordana T.; Mill, Jonathan; Caspi, Avshalom; Martin, Nicholas G.; Boomsma, Dorret, I., and School of Medicine

Abstract

The mechanisms underlying how monozygotic (or identical) twins arise are yet to be determined. Here, the authors investigate this in an epigenome-wide association study, showing that monozygotic twinning has a characteristic DNA methylation signature in adult somatic tissues. Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin., Netherlands Organization for Scientific Research (NWO) Biobanking and Biomolecular Research Infrastructure; NWO Large Scale infrastructures, X-Omics

Published
2021

49. A mammalian methylation array for profiling methylation levels at conserved sequences

Author

Arneson, Adriana, primary, Haghani, Amin, additional, Thompson, Michael J., additional, Pellegrini, Matteo, additional, Kwon, Soo Bin, additional, Vu, Ha, additional, Yao, Mingjia, additional, Li, Caesar Z., additional, Lu, Ake T., additional, Barnes, Bret, additional, Hansen, Kasper D., additional, Zhou, Wanding, additional, Breeze, Charles E., additional, Ernst, Jason, additional, and Horvath, Steve, additional

Published
2021
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50. Comparison of phenotypes and outcomes following resection of incidental versus symptomatic pancreatic neuroendocrine tumors

Author

Hurtado-Pardo, Luis, primary, Breeze, Charles E., additional, Cienfuegos, Javier A, additional, Benito, Alberto, additional, Azcárate, Víctor, additional, Martí-Cruchaga, Pablo, additional, Zozaya, Gabriel, additional, Martínez Regueira, Fernando, additional, Pardo, Fernando, additional, and Rotellar Sastre, Fernando, additional

Published
2021
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