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1. Simultaneous sequencing of genetic and epigenetic bases in DNA

Author

Füllgrabe, Jens, Gosal, Walraj S., Creed, Páidí, Liu, Sidong, Lumby, Casper K., Morley, David J., Ost, Tobias W. B., Vilella, Albert J., Yu, Shirong, Bignell, Helen, Burns, Philippa, Charlesworth, Tom, Fu, Beiyuan, Fordham, Howerd, Harding, Nicolas J., Gandelman, Olga, Golder, Paula, Hodson, Christopher, Li, Mengjie, Lila, Marjana, Liu, Yang, Mason, Joanne, Mellad, Jason, Monahan, Jack M., Nentwich, Oliver, Palmer, Alexandra, Steward, Michael, Taipale, Minna, Vandomme, Audrey, San-Bento, Rita Santo, Singhal, Ankita, Vivian, Julia, Wójtowicz, Natalia, Williams, Nathan, Walker, Nicolas J., Wong, Nicola C. H., Yalloway, Gary N., Holbrook, Joanna D., and Balasubramanian, Shankar

Published
2023
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2. Hydroxymethylation profile of cell-free DNA is a biomarker for early colorectal cancer

Author

Walker, Nicolas J., Rashid, Mamunur, Yu, Shirong, Bignell, Helen, Lumby, Casper K., Livi, Carmen M., Howell, Kate, Morley, David J., Morganella, Sandro, Barrell, Daniel, Caim, Shabhonam, Gosal, Walraj, Füllgrabe, Jens, Charlesworth, Thomas J., Vasquez, Louella, Ahdesmäki, Miika, Eizenga, Jordan, Prabhat, Parul, Proutski, Vitali, Murat-Onana, Marie Laurie, Greenwood, Catherine J., Kirkwood, Lisa, Maisuria-Armer, Meeta, Li, Mengjie, Coats, Emma, Winfield, Victoria, MacBean, Lachlan, Stock, Toby, Tomé-Fernandez, Alice, Chan, Yat, Sheikh, Nasir, Golder, Paula, Steward, Michael, Ost, Tobias W. B., Stewart, Douglas, Vilella, Albert, Noursalehi, Mojtaba, Paten, Benedict, Lucarelli, Debora, Mason, Joanne, Ridge, Gareth, Mellad, Jason, Shirodkar, Suman, Balasubaramanian, Shankar, and Holbrook, Joanna D.

Published
2022
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3. Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk

Author

Qiu, Anqi, Shen, Mojun, Buss, Claudia, Chong, Yap-Seng, Kwek, Kenneth, Saw, Seang-Mei, Gluckman, Peter D, Wadhwa, Pathik D, Entringer, Sonja, Styner, Martin, Karnani, Neerja, Heim, Christine M, O'Donnell, Kieran J, Holbrook, Joanna D, Fortier, Marielle V, and Meaney, Michael J

Subjects
Brain Disorders, Pediatric, Behavioral and Social Science, Mind and Body, Depression, Neurosciences, Mental Health, Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Mental health, Neurological, Reproductive health and childbirth, Good Health and Well Being, Asians, Brain, Brain Mapping, Cohort Studies, Computational Biology, Depressive Disorder, Major, Female, Fetal Development, Gene Regulatory Networks, Genotype, Gestational Age, Humans, Image Processing, Computer-Assisted, Infant, Newborn, Magnetic Resonance Imaging, Male, Maternal-Fetal Relations, Polymorphism, Single Nucleotide, Pregnancy, Prenatal Exposure Delayed Effects, Social Class, amygdala, cortical thickness, depression, morphological shape, polygenic risk score, the GUSTO study group, Asian People, Psychology, Cognitive Sciences, Experimental Psychology
Abstract

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development.

Published
2017

5. Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood

Author

Lillycrop, Karen A., Garratt, Emma S., Titcombe, Philip, Melton, Phillip E., Murray, Robert J. S., Barton, Sheila J., Clarke-Harris, Rebecca, Costello, Paula M., Holbrook, Joanna D., Hopkins, James C., Childs, Caroline E., Paras-Chavez, Carolina, Calder, Philip C., Mori, Trevor A., Beilin, Lawrie, Burdge, Graham C., Gluckman, Peter D., Inskip, Hazel M., Harvey, Nicholas C., Hanson, Mark A., Huang, Rae-Chi, Cooper, Cyrus, EpiGen Consortium, and Godfrey, Keith M.

Published
2019
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7. Abstract 6602: Refining liquid biopsy: generating more information from cell free DNA

Author

Puddu, Fabio, primary, Lumby, Casper K., additional, Harding, Nick, additional, Morley, David J., additional, Scotcher, Jamie, additional, Crawford, Robert, additional, Füllgrabe, Jens, additional, Gosal, Walraj S., additional, Yu, Shirong, additional, Brudzewsky, Daniel, additional, Haywood, Jane, additional, Tomoni, Andrada, additional, Burns, Philippa, additional, Holbrook, Joanna D., additional, and Creed, Paidi, additional

Published
2023
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13. Data from Parkin Pathway Activation Mitigates Glioma Cell Proliferation and Predicts Patient Survival

Author

Yeo, Calvin W.S., primary, Ng, Felicia S.L., primary, Chai, Chou, primary, Tan, Jeanne M.M., primary, Koh, Geraldene R.H., primary, Chong, Yuk Kien, primary, Koh, Lynnette W.H., primary, Foong, Charlene S.F., primary, Sandanaraj, Edwin, primary, Holbrook, Joanna D., primary, Ang, Beng-Ti, primary, Takahashi, Ryosuke, primary, Tang, Carol, primary, and Lim, Kah-Leong, primary

Published
2023
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14. Supplementary Tables 1-3 from Parkin Pathway Activation Mitigates Glioma Cell Proliferation and Predicts Patient Survival

Author

Yeo, Calvin W.S., primary, Ng, Felicia S.L., primary, Chai, Chou, primary, Tan, Jeanne M.M., primary, Koh, Geraldene R.H., primary, Chong, Yuk Kien, primary, Koh, Lynnette W.H., primary, Foong, Charlene S.F., primary, Sandanaraj, Edwin, primary, Holbrook, Joanna D., primary, Ang, Beng-Ti, primary, Takahashi, Ryosuke, primary, Tang, Carol, primary, and Lim, Kah-Leong, primary

Published
2023
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15. Supplementary Figures 1-8 from Parkin Pathway Activation Mitigates Glioma Cell Proliferation and Predicts Patient Survival

Author

Yeo, Calvin W.S., primary, Ng, Felicia S.L., primary, Chai, Chou, primary, Tan, Jeanne M.M., primary, Koh, Geraldene R.H., primary, Chong, Yuk Kien, primary, Koh, Lynnette W.H., primary, Foong, Charlene S.F., primary, Sandanaraj, Edwin, primary, Holbrook, Joanna D., primary, Ang, Beng-Ti, primary, Takahashi, Ryosuke, primary, Tang, Carol, primary, and Lim, Kah-Leong, primary

Published
2023
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16. Supplementary Methods, Figure Legends 1-8 from Parkin Pathway Activation Mitigates Glioma Cell Proliferation and Predicts Patient Survival

Author

Yeo, Calvin W.S., primary, Ng, Felicia S.L., primary, Chai, Chou, primary, Tan, Jeanne M.M., primary, Koh, Geraldene R.H., primary, Chong, Yuk Kien, primary, Koh, Lynnette W.H., primary, Foong, Charlene S.F., primary, Sandanaraj, Edwin, primary, Holbrook, Joanna D., primary, Ang, Beng-Ti, primary, Takahashi, Ryosuke, primary, Tang, Carol, primary, and Lim, Kah-Leong, primary

Published
2023
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17. Maternal dysglycaemia, changes in the infant's epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial

Author

Antoun, Elie, Kitaba, Negusse T., Titcombe, Philip, Dalrymple, Kathryn V., Garratt, Emma S., Barton, Sheila J., Murray, Robert, Seed, Paul T., Holbrook, Joanna D., Kobor, Michael S., Lin, David TS, MacIsaac, Julia L., Burdge, Graham C., White, Sara L., Poston, Lucilla, Godfrey, Keith M., and Lillycrop, Karen A.

Subjects
Blood sugar -- Health aspects, Pregnant women -- Care and treatment, Infants (Newborn) -- Health aspects -- Genetic aspects, Biological sciences
Abstract

Background Higher maternal plasma glucose (PG) concentrations, even below gestational diabetes mellitus (GDM) thresholds, are associated with adverse offspring outcomes, with DNA methylation proposed as a mediating mechanism. Here, we examined the relationships between maternal dysglycaemia at 24 to 28 weeks' gestation and DNA methylation in neonates and whether a dietary and physical activity intervention in pregnant women with obesity modified the methylation signatures associated with maternal dysglycaemia. Methods and findings We investigated 557 women, recruited between 2009 and 2014 from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial (RCT), of a lifestyle intervention (low glycaemic index (GI) diet plus physical activity) in pregnant women with obesity (294 contol, 263 intervention). Between 27 and 28 weeks of pregnancy, participants had an oral glucose (75 g) tolerance test (OGTT), and GDM diagnosis was based on diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), with 159 women having a diagnosis of GDM. Cord blood DNA samples from the infants were interrogated for genome-wide DNA methylation levels using the Infinium Human MethylationEPIC BeadChip array. Robust regression was carried out, adjusting for maternal age, smoking, parity, ethnicity, neonate sex, and predicted cell-type composition. Maternal GDM, fasting glucose, 1-h, and 2-h glucose concentrations following an OGTT were associated with 242, 1, 592, and 17 differentially methylated cytosine-phosphate-guanine (dmCpG) sites (false discovery rate (FDR) [less than or equal to] 0.05), respectively, in the infant's cord blood DNA. The most significantly GDM-associated CpG was cg03566881 located within the leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) (FDR = 0.0002). Moreover, we show that the GDM and 1-h glucose-associated methylation signatures in the cord blood of the infant appeared to be attenuated by the dietary and physical activity intervention during pregnancy; in the intervention arm, there were no GDM and two 1-h glucose-associated dmCpGs, whereas in the standard care arm, there were 41 GDM and 160 1-h glucose-associated dmCpGs. A total of 87% of the GDM and 77% of the 1-h glucose-associated dmCpGs had smaller effect sizes in the intervention compared to the standard care arm; the adjusted r.sup.2 for the association of LGR6 cg03566881 with GDM was 0.317 (95% confidence interval (CI) 0.012, 0.022) in the standard care and 0.240 (95% CI 0.001, 0.015) in the intervention arm. Limitations included measurement of DNA methylation in cord blood, where the functional significance of such changes are unclear, and because of the strong collinearity between treatment modality and severity of hyperglycaemia, we cannot exclude that treatment-related differences are potential confounders. Conclusions Maternal dysglycaemia was associated with significant changes in the epigenome of the infants. Moreover, we found that the epigenetic impact of a dysglycaemic prenatal maternal environment appeared to be modified by a lifestyle intervention in pregnancy. Further research will be needed to investigate possible medical implications of the findings. Trial registration ISRCTN89971375., Author(s): Elie Antoun 1, Negusse T. Kitaba 2, Philip Titcombe 3, Kathryn V. Dalrymple 4, Emma S. Garratt 2,5, Sheila J. Barton 3, Robert Murray 2, Paul T. Seed 4, [...]

Published
2020
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18. Association of physical activity and sedentary behavior with depression and anxiety symptoms during pregnancy in a multiethnic cohort of Asian women

Author

Padmapriya, Natarajan, Bernard, Jonathan Y., Liang, Shen, Loy, See Ling, Shen, Zhe, Kwek, Kenneth, Godfrey, Keith M., Gluckman, Peter D., Chong, Yap-Seng, Saw, Seang Mei, Meaney, Michael J., Chen, Helen, Müller-Riemenschneider, Falk, Agarwal, Pratibha, Biswas, Arijit, Bong, Choon Looi, Broekman, Birit F. P., Cai, Shirong, Chan, Jerry Kok Yen, Chan, Yiong Huak, Chee, Cornelia Yin Ing, Cheung, Yin Bun, Chinnadurai, Amutha, Chng, Chai Kiat, Chong, Mary Foong-Fong, Chong, Shang Chee, Chua, Mei Chien, Fok, Doris, Fortier, Marielle V., Goh, Anne Eng Neo, Goh, Yam Thiam Daniel, Gooley, Joshua J., Han, Wee Meng, Hanson, Mark, Henry, Christiani Jeyakumar, Holbrook, Joanna D., Hsu, Chin-Ying, Karnani, Neerja, Kapur, Jeevesh, Lau, Ivy Yee-Man, Lee, Bee Wah, Lee, Yung Seng, Lek, Ngee, Lim, Sok Bee, Magiati, Iliana, Daniel, Lourdes Mary, Ngo, Cheryl, Niduvaje, Krishnamoorthy, Pang, Wei Wei, Qiu, Anqi, Quah, Boon Long, Rajadurai, Victor Samuel, Rauff, Mary, Rebello, Salome A., Richmond, Jenny L., Rifkin-Graboi, Anne, Shek, Lynette Pei-Chi, Sheppard, Allan, Shuter, Borys, Singh, Leher, Soh, Shu-E, Stunkel, Walter, Su, Lin Lin, Tan, Kok Hian, Teoh, Oon Hoe, Tint, Mya Thway, van Bever, Hugo P. S., van Dam, Rob M., Wong, Inez Bik Yun, Wong, P. C., Yap, Fabian, Yeo, George Seow Heong, and On behalf of the GUSTO Study Group

Published
2016
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19. Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescence.

Author

Melton, Phillip E, primary, Burton, Mark A, additional, Lillycrop, Karen, additional, Godfrey, Keith M, additional, Rauschert, Sebastian, additional, Anderson, Denise, additional, Burdge, Graham C, additional, Mori, Trevor A, additional, Beilin, Lawrence J, additional, Ayonrinde, Oyekoya T, additional, Craig, Jeffery M, additional, Olynyk, John K, additional, Holbrook, Joanna D, additional, Pennell, Craig E, additional, Oddy, Wendy H, additional, Moses, Eric K, additional, Adams, Leon A, additional, and Huang, Rae-Chi, additional

Published
2022
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23. Accurate simultaneous sequencing of genetic and epigenetic bases in DNA

Author

Füllgrabe, Jens, primary, Gosal, Walraj S, additional, Creed, Páidí, additional, Liu, Sidong, additional, Lumby, Casper K, additional, Morley, David J, additional, Ost, Tobias W B, additional, Vilella, Albert J, additional, Yu, Shirong, additional, Bignell, Helen, additional, Burns, Philippa, additional, Charlesworth, Tom, additional, Fu, Beiyuan, additional, Fordham, Howerd, additional, Harding, Nick, additional, Gandelman, Olga, additional, Golder, Paula, additional, Hodson, Christopher, additional, Li, Mengjie, additional, Lila, Marjana, additional, Liu, Yang, additional, Mason, Joanne, additional, Mellad, Jason, additional, Monahan, Jack, additional, Nentwich, Oliver, additional, Palmer, Alexandra, additional, Steward, Michael, additional, Taipale, Minna, additional, Vandomme, Audrey, additional, San-Bento, Rita Santo, additional, Singhal, Ankita, additional, Vivian, Julia, additional, Wójtowicz, Natalia, additional, Williams, Nathan, additional, Walker, Nicolas J, additional, Wong, Nicola C H, additional, Yalloway, Gary, additional, Holbrook, Joanna D, additional, and Balasubaramanian, Shankar, additional

Published
2022
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24. DNA methylome variation in a perinatal nurse-visitation program that reduces child maltreatment: a 27-year follow-up

Author

O’Donnell, Kieran J., Chen, Li, MacIsaac, Julia L., McEwen, Lisa M., Nguyen, Thao, Beckmann, Katherine, Zhu, Yuecai, Chen, Lawrence Ming, Brooks-Gunn, Jeanne, Goldman, David, Grigorenko, Elena L., Leckman, James F., Diorio, Josie, Karnani, Neerja, Olds, David L., Holbrook, Joanna D., Kobor, Michael S., and Meaney, Michael J.

Published
2018
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29. Human non-CpG methylation patterns display both tissue-specific and inter-individual differences suggestive of underlying function

Author

Titcombe, Philip, primary, Murray, Robert, additional, Hewitt, Matthew, additional, Antoun, Elie, additional, Cooper, Cyrus, additional, Inskip, Hazel M, additional, Holbrook, Joanna D, additional, Godfrey, Keith M, additional, Lillycrop, Karen, additional, Hanson, Mark, additional, and Barton, Sheila J, additional

Published
2021
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32. Cohort Profile: Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study

Author

Soh, Shu-E, Tint, Mya Thway, Gluckman, Peter D, Godfrey, Keith M, Rifkin-Graboi, Anne, Chan, Yiong Huak, Stünkel, Walter, Holbrook, Joanna D, Kwek, Kenneth, Chong, Yap-Seng, Saw, Seang Mei, Sheppard, Allan, Chinnadurai, Amutha, Ferguson-Smith, Anne, Goh, Anne Eng Neo, Biswas, Arijit, Chia, Audrey, Leutscher-Broekman, Birit, Shuter, Borys, Cai, Shirong, Ngo, Cheryl, Chng, Chai Kiat, Chong, Shang Chee, Henry, Christiani Jeyakumar, Chua, Mei Chien, Chee, Cornelia Yin Ing, Goh, Yam Thiam Daniel, Bier, Dennis, Ding, Chun Ming, Fok, Doris, Finkelstein, Eric Andrew, Yap, Fabian Kok Peng, Yeo, George Seow Heong, Han, Wee Meng, Chen, Helen, Van Bever, Hugo P S, Inskip, Hazel, Magiati, Iliana, Wong, Inez Bik Yun, Kapur, Jeevesh, Richmond, Jenny L, Chan, Jerry Kok Yen, Gooley, Joshua J, Niduvaje, Krishnamoorthy, Lee, Bee Wah, Lee, Yung Seng, Singh, Leher, Lim, Sok Bee, Daniel, Lourdes Mary, Loh, Seong Feei, Low, Yen-Ling, Shek, Pei-Chi Lynette, Fortier, Marielle, Hanson, Mark, Chong, Mary Foong-Fong, Meaney, Michael, Morton, Susan, Pang, Wei Wei, Agarwal, Pratibha, Qiu, Anqi, Quah, Boon Long, van Dam, Rob M, Stringer, David, Rebello, Salome Antonette, So, Wing Chee, Hsu, Chin-Ying, Su, Lin Lin, Tang, Jenny, Tan, Kok Hian, Tan, Soek Hui, Teoh, Oon Hoe, Rajadurai, Victor Samuel, Wong, PC, and Venkatesh, Sudhakar K

Published
2014
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35. Human non-CpG methylation patterns display both tissue-specific and inter-individual differences suggestive of underlying function.

Author

Titcombe, Philip, Murray, Robert, Hewitt, Matthew, Antoun, Elie, Cooper, Cyrus, Inskip, Hazel M, Holbrook, Joanna D, Godfrey, Keith M, Lillycrop, Karen, Hanson, Mark, and Barton, Sheila J

Subjects
CORD blood, METHYLATION, DNA methylation, HIERARCHICAL clustering (Cluster analysis), CLUSTER analysis (Statistics), HUMAN genome, TISSUES
Abstract

DNA methylation (DNAm) in mammals is mostly examined within the context of CpG dinucleotides. Non-CpG DNAm is also widespread across the human genome, but the functional relevance, tissue-specific disposition, and inter-individual variability has not been widely studied. Our aim was to examine non-CpG DNAm in the wider methylome across multiple tissues from the same individuals to better understand non-CpG DNAm distribution within different tissues and individuals and in relation to known genomic regulatory features. DNA methylation in umbilical cord and cord blood at birth, and peripheral venous blood at age 12–13 y from 20 individuals from the Southampton Women's Survey cohort was assessed by Agilent SureSelect methyl-seq. Hierarchical cluster analysis (HCA) was performed on CpG and non-CpG sites and stratified by specific cytosine environment. Analysis of tissue and inter-individual variation was then conducted in a second dataset of 12 samples: eight muscle tissues, and four aliquots of cord blood pooled from two individuals. HCA using methylated non-CpG sites showed different clustering patterns specific to the three base-pair triplicate (CNN) sequence. Analysis of CAC sites with non-zero methylation showed that samples clustered first by tissue type, then by individual (as observed for CpG methylation), while analysis using non-zero methylation at CAT sites showed samples grouped predominantly by individual. These clustering patterns were validated in an independent dataset using cord blood and muscle tissue. This research suggests that CAC methylation can have tissue-specific patterns, and that individual effects, either genetic or unmeasured environmental factors, can influence CAT methylation. [ABSTRACT FROM AUTHOR]

Published
2022
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36. ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity

Author

Lillycrop, Karen, Murray, Robert, Cheong, Clara, Teh, Ai Ling, Clarke-Harris, Rebecca, Barton, Sheila, Costello, Paula, Garratt, Emma, Cook, Eloise, Titcombe, Philip, Shunmuganathan, Bhuvaneshwari, Liew, Samantha J., Chua, Yong-Cai, Lin, Xinyi, Wu, Yonghui, Burdge, Graham C., Cooper, Cyrus, Inskip, Hazel M., Karnani, Neerja, Hopkins, James C., Childs, Caroline E., Chavez, Carolina Paras, Calder, Philip C., Yap, Fabian, Lee, Yung Seng, Chong, Yap Seng, Melton, Philip E., Beilin, Lawrie, Huang, Rae-Chi, Gluckman, Peter D., Harvey, Nick, Hanson, Mark A., Holbrook, Joanna D., Godfrey, Keith M., and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
Adult, Male, Adolescent, lcsh:Medicine, Epigenesis, Genetic, Young Adult, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p18, Humans, Science::Medicine [DRNTU], Obesity, Child, Promoter Regions, Genetic, Cyclin-Dependent Kinase Inhibitor p16, Aged, Adiposity, lcsh:R5-920, DNA methylation, lcsh:R, Infant, Newborn, Infant, Epigenetic, Middle Aged, DNA Methylation, CpG Islands, Female, RNA, Long Noncoding, lcsh:Medicine (General), Biomarkers, Research Paper
Abstract

Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health., Highlights • DNA methylation within the ANRIL promoter region was predictive of measures of adiposity in four independent cohorts. • DNA methylation may be a marker for late gestation fetal undernutrition, followed by rapid postnatal weight gain. • Altered DNA methylation associated with p16INK4a and p14ARF expression. • ERα may bind at the ANRIL promoter, and in vitro E2 treatment stimulated expression of ANRIL, while reducing p14 expression. The quality of the early life environment before birth can affect susceptibility to metabolic disease later in the lifecourse, with epigenetic regulation of gene function thought to be one mechanism through which early life environmental factors induce persistent phenotypic changes. In this study, using DNA from the Southampton Women's Survey (SWS), we identified changes in DNA methylation levels at birth that associated with adiposity later in childhood within the promoter of ANRIL, a gene with strong disease associations that is involved in regulatiing cellular growth. This finding was replicated in several independent cohorts, and functionally validated in adipocyte cells.

Published
2017

37. Perinatal DNA Methylation at CDKN2A Is Associated With Offspring Bone Mass: Findings From the Southampton Women's Survey

Author

Curtis, Elizabeth M., Murray, Robert, Titcombe, Philip, Cook, Eloise, Clarke-Harris, Rebecca, Costello, Paula, Garratt, Emma, Holbrook, Joanna D., Barton, Sheila, Inskip, Hazel, Godfrey, Keith M., Bell, Christopher G., Cooper, Cyrus, Lillycrop, Karen A., and Harvey, Nicholas C.

Subjects
DXA, Adult, Osteosarcoma, Infant, Newborn, Original Articles, Organ Size, DNA Methylation, OSTEOPOROSIS, Health Surveys, Bone and Bones, United Kingdom, EPIGENETICS, Cohort Studies, CDKN2A, DEVELOPMENT, Calcification, Physiologic, Bone Density, Cell Line, Tumor, EPIDEMIOLOGY, Cyclin-Dependent Kinase Inhibitor p18, Humans, Original Article, CpG Islands, Female, Cyclin-Dependent Kinase Inhibitor p16
Abstract

Poor intrauterine and childhood growth has been linked with the risk of osteoporosis in later life, a relationship that may in part be mediated through altered epigenetic regulation of genes. We previously identified a region within the promoter of the long non‐coding RNA ANRIL encoded by the CDKN2A locus, at which differential DNA methylation at birth showed correlations with offspring adiposity. Given the common lineage of adipocytes and osteoblasts, we investigated the relationship between perinatal CDKN2A methylation and bone mass at ages 4 and 6 years. Using sodium bisulfite pyrosequencing, we measured the methylation status of the 9 CpGs within this region in umbilical cord samples from discovery (n = 332) and replication (n = 337) cohorts of children from the Southampton Women's Survey, whose bone mass was assessed by dual‐energy X‐ray absorptiomietry (DXA; Hologic Discovery). Inverse associations were found between perinatal CDKN2A methylation and whole‐body minus head bone area (BA), bone mineral content (BMC), and areal bone mineral density (BMD). This was confirmed in replication and combined data sets (all p

Published
2017

39. Epigenome‐wide association study of sarcopenia: findings from the Hertfordshire Sarcopenia Study (HSS).

Author

Antoun, Elie, Garratt, Emma S., Taddei, Andrea, Burton, Mark A., Barton, Sheila J., Titcombe, Phil, Westbury, Leo D., Baczynska, Alicia, Migliavacca, Eugenia, Feige, Jerome N., Sydall, Holly E., Dennison, Elaine, Dodds, Richard, Roberts, Helen C., Richardson, Peter, Sayer, Avan A., Shaw, Sarah, Cooper, Cyrus, Holbrook, Joanna D., and Patel, Harnish P.

Published
2022
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40. Contributors

Author

Adachi, Hideki, primary, Adachi, Osao, additional, Adam, Zach, additional, Adams, Michael W.W., additional, Adang, Michael J., additional, Adham, Ibrahim M., additional, Aducci, Patrizia, additional, Agard, David A., additional, Agranovsky, Alexey A., additional, Ahn, Kyunghye, additional, Akiyama, Yoshinori, additional, Alejo, Alí, additional, Amberg, Sean M., additional, Amerik, Alexander Y., additional, Andrés, Germán, additional, Andrews, Robert K., additional, Antalis, Toni M., additional, Apte, Suneel S., additional, Arima, Kazunari, additional, Arlaud, Gérard J., additional, Aronson, Nathan N., additional, Asano, Yasuhisa, additional, Ascenzi, Paolo, additional, Assakura, Marina T., additional, Auld, David S., additional, Avilés, Francesc X., additional, Awad, William M., additional, Babé, Lilia M., additional, Badorff, Cornel, additional, Bai, Shan, additional, Baird, Teaster T., additional, Paul Bajaj, S., additional, Baker, Rohan T., additional, Baker, Susan C., additional, Ballinger, Marcus D., additional, Banbula, Agnieszka, additional, Bannikov, Gregory A., additional, Barrett, Alan J., additional, Bartlett, John D., additional, Baskova, Isolda P., additional, Bauer, Karl, additional, Baumann, Ulrich, additional, Baumeister, Wolfgang, additional, Beauvais, Anne, additional, Belas, Robert, additional, Beppu, Teruhiko, additional, Bergmann, Ernst M., additional, Bergo, Martin O., additional, Berndt, Michael C., additional, Berry, Colin, additional, Bertenshaw, Greg P., additional, Betzel, Ch., additional, Bierbaum, Gabriele, additional, Bieth, Joseph G., additional, Bjarnason, Jón B., additional, Blaber, M., additional, Blaber, S.I., additional, Black, Roy A., additional, Blackman, M.J., additional, Blinkovsky, Alexander, additional, Blobel, Carl P., additional, Boatright, Kelly M., additional, Böck, August, additional, Boeke, Jef D., additional, Boileau, Guy, additional, Bolken, Tové C., additional, Bond, Judith S., additional, Bordallo, Javier, additional, Bordusa, Frank, additional, Boucaut, Kerry J., additional, Bouvier, Jacques, additional, Bowman, Barry J., additional, Bradshaw, Ralph A., additional, Braun, Hans-Peter, additional, Breddam, Klaus, additional, Brindley, Paul J., additional, Broadhurst, Anne, additional, Brocklehurst, Keith, additional, Broder, Dan H., additional, Brömme, Dieter, additional, Bron, Sierd, additional, Broom, Murray, additional, Brown, Kenneth D., additional, Brown, Mark A., additional, Bunn, Rhonda, additional, Burleigh, Barbara A., additional, Butler, Michael J., additional, Buttle, David J., additional, Byrd, Chelsea M., additional, Byun, Tony, additional, Cadel, Sandrine, additional, Caffrey, Conor R., additional, Caldentey, Javier, additional, Caprioglio, Daniel R., additional, Carbonell, Juan, additional, Carpentier, Mélanie, additional, Carter, Ruth E., additional, Casey, Patrick J., additional, Castellino, Francis J., additional, Catanese, Joseph J., additional, Caterson, Bruce, additional, Caughey, George H., additional, Cawley, Niamh X., additional, Cawston, Tim E., additional, Jose Cazzulo, Juan, additional, Cercós, Manuel, additional, Chakraborty, Trinad, additional, Chambers, Henry F., additional, Chang, L.S., additional, Chan, Michael K., additional, Chan, Sunney I., additional, Chao, Julie, additional, Chapot-Chartier, Marie-Pierre, additional, Chave, Karen J., additional, Chen, Jian-Min, additional, Chen, Jinq-May, additional, Chesneau, Valérie, additional, Chevrier, Bernard, additional, Chich, Jean-François, additional, Yong Choi, Kwan, additional, Chrétien, Michel, additional, Ha Chung, Chin, additional, Chung, Dominic W., additional, Clamagirand, Christine, additional, Clark, Ian M., additional, Clarke, Adrian K., additional, Clarke, Steven, additional, Cleary, Paul P., additional, Clements, Judith A., additional, Cleuziat, Philippe, additional, Cohen, Paul, additional, Colige, Alain, additional, Collen, D., additional, Collier, Ivan E., additional, Colloms, Sean D., additional, Colman, Robert W., additional, Conner, Gregory E., additional, Conzelmann, Andreas, additional, Coolbear, Tim, additional, Coombs, Graham H., additional, Cooper, Jonathan B., additional, Cooper, Max D., additional, Copeland, Nikki A., additional, Corvol, Pierre, additional, Cottrell, Graeme S., additional, Coyle, Joseph T., additional, Craik, Charles S., additional, Creemers, John W.M., additional, Croce, Jenifer, additional, Cueva, Rosario, additional, Cutting, Simon, additional, d′Enfert, Christophe, additional, D′Orchymont, Hugues, additional, Daenke, S., additional, Dahlbäck, Björn, additional, Dalbey, Ross E., additional, Dalton, John P., additional, Dando (Deceased), Pamela M., additional, Daniel, R.M., additional, Darke, Paul L., additional, Lagerblad de Oliveira, Pedro, additional, de Vos, Sarah, additional, Deghmane, Ala-Eddine, additional, Dekker, Niek, additional, DeLotto, Robert, additional, DeMartino, George N., additional, den Boon, Johan A., additional, Denison, Mark R., additional, DesGroseillers, Luc, additional, Deussing, Jan, additional, Devi, Lakshmi A., additional, Diamandis, Eleftherios P., additional, Dickson, Robert B., additional, Dingwall, Colin, additional, Dixon, Jack E., additional, Dodt, Johannes, additional, Dolenc, Iztoc, additional, Cat Dong, Tran, additional, Dong, Ying, additional, Dubois, Jean-Yves F., additional, Dudley, Edward G., additional, Dunn, Ben M., additional, Dupuy, Bruno, additional, Conceicão Duque-Magalhães, Maria, additional, Eeckhout, Yves, additional, Egelrud, Torbjörn, additional, Eijsink, Vincent, additional, Ellis, Vincent, additional, Engel, Wolfgang, additional, Erdös, Ervin G., additional, Etscheid, Michael, additional, Evans (Deceased), Herbert J., additional, Everett, Roger D., additional, Eyries, Mélanie, additional, Fahrenholz, Falk, additional, Fenster, Kurt M., additional, Férec, Claude, additional, Henrique Ferreira Sorgine, Marcos, additional, Fink, Doran, additional, Fives-Taylor, Paula M., additional, Foltmann, Bent, additional, Foster, Simon J., additional, Foulon, Thierry, additional, Foundling, Stephen I., additional, Fox, Jay W., additional, Freeze, Hudson H., additional, Frère, Jean-Marie, additional, Frey, Teryl K., additional, Flicker, Lloyd D., additional, Fritsche, Erich, additional, Froelich, Christopher J., additional, Fuhrmann, Cynthia N., additional, Fujimura, Satoshi, additional, Fukushima, J., additional, Fuller, Robert S., additional, Gaboriaud, Christine, additional, Gache, Christian, additional, Galivan, John, additional, Gary, Jonathan D., additional, Gaucher, G.M., additional, Ghuysen, Jean-Marie, additional, Gil, María J., additional, Giller, Thomas, additional, Goffin, Colette, additional, Gohda, Eiichi, additional, Goldberg, Alfred L., additional, Goldberg, Daniel E., additional, Goldberg, Gregory I., additional, Gorbalenya, Alexander E., additional, Gordon, Stuart G., additional, Götz, Friedrich, additional, Gráf, László, additional, Granados, Robert R., additional, Granell, Antonio, additional, Graycar, Thomas P., additional, Green, Jonathan, additional, Greenspan, Daniel S., additional, Grubman, Marvin J., additional, Grunden, Amy M., additional, Guillemain, Bernard, additional, Guinand, Micheline, additional, Gutiérrez, José Maria, additional, Haeggström, Jesper Z., additional, Hageman, James H., additional, Hagmann, Marie-Luise, additional, Halfon, Sherin, additional, Hamilton, Andrew J., additional, Seon Han, Ji, additional, Hara-Nishimura, Ikuko, additional, Harada, Minoru, additional, Hartzell, William O., additional, Hay, Rod J., additional, Hayashi, Kiyoshi, additional, Hendriks, Dirk F., additional, Henrich, Bernhard, additional, Henriet, Patrick, additional, Hernández-Arana, Andrés, additional, Herrera-Camacho, Irma, additional, Heusipp, Gerhard, additional, Hicks, P.M., additional, Hillman, Bradley I., additional, Yukihiro Hiraoka, B., additional, Hiratake, Jun, additional, Ho, Heng-Chien, additional, Thi Hoa, Ngo, additional, Hochstrasser, Mark, additional, Hofmann, Theo, additional, Hohn, Thomas, additional, Hoidal, John R., additional, Holbrook, Joanna D., additional, Höltje, Joachim-Volker, additional, Homma, Koichi J., additional, Hook, Vivian Y.H., additional, Hooper, John D., additional, Hooper, Nigel M., additional, Hosoi, Kazuo, additional, Hospital, Véronique, additional, Howe, Christopher J., additional, Hruby, Dennis E., additional, Huang, H.-C., additional, Huber, Robert, additional, Hughes, Clare E., additional, Ibrahim-Granet, Oumaïma, additional, Ichishima, Eiji, additional, Ikehara, Yukio, additional, Imamura, Takahisa, additional, Inagaki, Noritoshi, additional, Inagami, Tadashi, additional, Isaac, R.E., additional, Isaya, Grazia, additional, Ishihara, Kohji, additional, Ishii, Shin-ichi, additional, Itoh, Yoshifumi, additional, Ito, Kiyoshi, additional, Ito, Koreaki, additional, Iwanaga, Sadaaki, additional, Jack, Ralph W., additional, Jackson, Mel C., additional, James, Michael N.G., additional, Jeffrey (Deceased), John, additional, Jiang, Ping, additional, Johnson, Gary D., additional, Johnson, John E., additional, Johnson, Michael, additional, Albert Johnston, Stephen, additional, Jones, Elizabeth W., additional, Jongbloed, Jan D.H., additional, Joshua-Tor, Leemor, additional, Joudiou, Carine, additional, Juliano, Luiz, additional, Jupp, Ray, additional, Kaminogawa, Shuichi, additional, Kamio, Yoshiyuki, additional, Kan, Chen-Chen, additional, Kaneda, Makoto, additional, Gyun Kang, Sung, additional, Kania, Mary, additional, Kanjanahaluethai, Amornrat, additional, Kawabata, Shun-ichiro, additional, Kay, John, additional, Keiler, Kenneth C., additional, Kelly, R.M., additional, Kerr, Michael A, additional, Kervinen, Jukka, additional, Kessler, Efrat, additional, Kidd, Simon, additional, Kilian, Mogens, additional, Kim, Do-Hyung, additional, Seop Kim, In, additional, Kimura, Yukio, additional, Kirisako, Takayoshi, additional, Kirschke, Heidrun, additional, Kishi, Tadaaki, additional, Kitamura, Naomi, additional, Kitazono, Ana A., additional, Kleanthous, Colin, additional, Klein, Jürgen R., additional, Kobayashi, Hideyuki, additional, Koelsch, Gerald, additional, Kok, Jan, additional, Kolattukudy, P.E., additional, Kolmar, Harald, additional, Komori, Yumiko, additional, Konvalinka, Jan, additional, Korhonen, Timo K., additional, Kortt, Alexander A., additional, Kräusslich, Hans-Georg, additional, Kress, Lawrence F., additional, Kubo, Takeaki, additional, Kukkonen, Maini, additional, Kumagai, Hidehiko, additional, Kumazaki, Takashi, additional, Kümmerer, Beate M., additional, Kuno, Kouji, additional, Kurachi, Kotoku, additional, Kurkinen, Markku, additional, Lähteenmäki, Kaarina, additional, Laing, Gavin D., additional, Lambkin, Imelda J., additional, Lamppa, Gayle K., additional, Lång, Hannu, additional, Langer, Thomas, additional, Laursen, Richard A., additional, Le Bonniec, Bernard F., additional, Luel Lee, Bok, additional, Joon Lee, Kye, additional, Young Lee, So, additional, Lee, Soohee, additional, Leis, Jonathan, additional, LeMosy, Ellen K., additional, Lepage, Thierry, additional, Leppla, Stephen H., additional, Lessard, Ivan A.D., additional, Lhomond, Guy, additional, Liao, Ta-Hsiu, additional, Lieber, Toby, additional, Lijnen, H.R., additional, Lima, Christopher D., additional, Lin, Chen-Yong, additional, Lin, Xinli, additional, Lindsay, L.L., additional, Lipscomb, William N., additional, Little, Christopher B., additional, Little, John W., additional, Lively, Mark O., additional, Lobel, Peter, additional, Peng Loh, Y., additional, Lohi, Jouko, additional, Lomonossoff, G.P., additional, Looze, Yvan, additional, López-García, Alma, additional, López-Otín, Carlos, additional, Luo, Liu-Ying, additional, Lupas, Andrei, additional, MacKay, Vivian L., additional, Mains, Richard E., additional, Mäkinen, Kauko K., additional, Mäkinen, Pirkko-Liisa, additional, Mandelbaum, Fajga R., additional, Manning, James M., additional, Marcotrigiano, Joseph, additional, Markland, Francis S., additional, Maruyama, M., additional, Maruyama, Sususmu, additional, Masaki, Takeharu, additional, Mathew, Zacharia, additional, Matrisian, Lynn M., additional, Matsuda, Yoshihiro, additional, Matsuka, Yury V., additional, Matsushita, Osamu, additional, Matsuzawa, Hiroshi, additional, Maurizi, Michael R., additional, Mbikay, Majambu, additional, Ken McDonald, J., additional, McKerrow, James H., additional, McMillan, David, additional, Mecham, Robert P., additional, Mehta, Darshini P., additional, Meighan, Paul, additional, Mellors, Alan, additional, Melton, Roger G., additional, Ménard, Armelle, additional, Ménard, Robert, additional, Menéndez-Arias, Luis, additional, Meyer, Diane H., additional, Meyers, Gregor, additional, Michaelis, Susan, additional, Mielicki, Wojciech P., additional, Mierau, Igor, additional, Millán-Pérez-Peña, Lourdes, additional, Miller, Charles G., additional, Mills, John, additional, Mills, Kenneth V., additional, Mistou, Michel-Yves, additional, Misumi, Yoshio, additional, Miyoshi, Shin-ichi, additional, Mizutani, Shigehiko, additional, Mock, William L., additional, Möhrlen, Frank, additional, Moiré, Nathalie, additional, Monnet, Véronique, additional, Monod, Michel, additional, Montecucco, Cesare, additional, Morita, Takashi, additional, Morrissey, James H., additional, Mort, John S., additional, Mortensen, Uffe H., additional, Morty, Rory E., additional, Motoshima, Hidemasa, additional, Mottram, Jeremy C., additional, Mundt, Egbert, additional, Murakami, Kazuo, additional, Murakami-Murofushi, Kimiko, additional, Murao, Sawao, additional, Murata, Christina, additional, Murphy, Gillian, additional, Muta, Tatsushi, additional, Mzhavia, Nino, additional, Nagase, Hideaki, additional, Naik, Rajesh R., additional, Nakajima, Nobuyoshi, additional, Nakamura, Hiroyuki, additional, Nakamura, Yukio, additional, Nasmyth, Kim, additional, Navarro-García, Fernando, additional, Netzel-Arnett, Sarah, additional, Nguyen-Distéche, Martine, additional, Nicholson, Donald, additional, Nikai, Toshiaki, additional, Nirasawa, Satoru, additional, Nishii, Wataru, additional, Nishiyama, Makoto, additional, Niven, Gordon W., additional, Nomura, Seiji, additional, Norioka, Shigemi, additional, North, Michael J., additional, Nuss, Donald L., additional, O′Connor, Michael B., additional, Oberst, Michael, additional, Oda, Kohei, additional, Odorico, Dimitri M., additional, Oetjen, Joyce, additional, Ogura, Teru, additional, Ohkubo, Iwao, additional, Ohlendorf, Douglas H., additional, Ohman, Dennis E., additional, Ohsumi, Yoshinori, additional, Okabe, Akinobu, additional, Okuda, K., additional, Olesen, Kjeld, additional, Oroszlan, Stephen, additional, Orth, Kim, additional, Ota, Nobuyuki, additional, Ovadia, Michael, additional, Overgaard, Michael T., additional, O-Wang, Jiyang, additional, Oxvig, Claus, additional, Packer, Jeremy C.L., additional, Paetzel, Mark, additional, Paine, Mark J.I., additional, Park, John E., additional, Woo Park, Pyong, additional, Soo Park, Sung, additional, Parkin, Kirk L., additional, Parks, William C., additional, Pascall, John C., additional, Paschos, Athanasios, additional, Paul, Sudhir, additional, Pearce, David A., additional, Pei, Duanqing, additional, Pemberton, Alan D., additional, Peters, Jan-Michael, additional, Phylip, Lowri H., additional, Pichová, Iva, additional, Pieper, Michael, additional, Piesse, Christophe, additional, Pike, Rob, additional, Pinck, Lothaire, additional, Pirzad, Ramin, additional, Pitot, Henry C., additional, Plaut, Andrew G., additional, Polgár, László, additional, Postina, Rolf, additional, Potempa, Jan, additional, Poulsen, Knud, additional, Pritchard, David G., additional, Pshezhetsky, Alexey V., additional, Abul Qasim, M., additional, Rader, Stephen D., additional, Rando, Robert R., additional, Rao, Mala, additional, Rao, Narayanam V., additional, Ratnoff, Oscar D., additional, Rawlings, Neil D., additional, Rawson, Robert B., additional, Reddy, Vijay, additional, Redman, Colvin M., additional, Reichl (Deceased), Antonia P., additional, Reid, Julian R., additional, Reid, Kenneth B.M., additional, Remaut, Han, additional, James Remington, S., additional, Rettig, Wolfgang J., additional, Rholam, Mohamed, additional, Rice, Charles M., additional, Richter, Stefan, additional, Riezman, Howard, additional, Ritchie, Alison, additional, Ro, Hyo-Sung, additional, Robert-Baudouy, Janine, additional, Michael Roberts, R., additional, Robinson, Michael, additional, Rodríguez-Romero, Adela, additional, Rogers, John C., additional, Rosenthal, Philip J., additional, Rose, A.M., additional, Rosing, J., additional, Rossetto, Ornella, additional, Rossi, Cesare, additional, Rossi, Véronique, additional, Roth, Richard A., additional, Rowan, Andrew D., additional, Rozanov, Mikhail, additional, Rucavado, Alexandra, additional, Rul, Françoise, additional, Rümenapf, Tillmann, additional, Ryan, Martin D., additional, Ryan, Thomas J., additional, Sacco, Elena, additional, Evan Sadler, J., additional, Saenger, W., additional, Sahl, Hans-Georg, additional, Sajid, Mohammed, additional, Sakiyama, Fumio, additional, Salas, María L., additional, Salter, Jason P., additional, Salvesen, Guy S., additional, Sanchez, Eladio F., additional, Sang, Qing-Xiang Amy, additional, Sankaran, Krishnan, additional, Sarras, Michael P., additional, Sasagawa, Yoshikiyo, additional, Satoh, Kimiyuki, additional, Sauer, Robert T., additional, Sawada, Hitoshi, additional, Scarisbrick, I.A., additional, Schauer-Vukasinovic, Vesna, additional, Schlievert, Patrick M., additional, Schlösser, Manfred, additional, Schmidt, Amy E., additional, Schmidt, Brian F., additional, Schmidt, Walter K., additional, Schmitz, Udo K., additional, Schneemann, Anette, additional, Scholze, Henning, additional, Schomburg, Lutz, additional, Schwaeble, Wilhelm J., additional, Sedlacek, Radislav, additional, Seemüller, Erika, additional, Seidah, Nabil G., additional, Seiki, Motoharu, additional, Selistre de Araujo, Heloisa S., additional, Senior, Robert M., additional, Sik Seong, Ihn, additional, Serpe, Mihaela, additional, Serrano, Solange M.T., additional, Setlow, Peter, additional, Shanks, M., additional, Shao, Feng, additional, Shapiro, Steven D., additional, Shen, Lei, additional, Sherwood (Deceased), Roger F., additional, Shi, Yun-Bo, additional, Shimoi, Hitoshi, additional, Shinoda, Sumio, additional, Siigur, Ene, additional, Siigur, Jüri, additional, Sim, Robert B., additional, Simmer, James P., additional, Simmons, William H., additional, Sirakova, Tatiana D., additional, Skern, Tim, additional, Skidgel, Randal A., additional, Slack, Jeffrey, additional, Sleat, David E., additional, Smith, Janet L., additional, Smyth, Mark J., additional, Snijder, Eric J., additional, Söderhäll, Kenneth, additional, Sohar, Istvan, additional, Sorimachi, Hiroyuki, additional, Sottrup-Jensen, Lars, additional, Soubrier, Florent, additional, Soukhodolets, Karen E., additional, Springman, Eric B., additional, Geme, Joseph W. St., additional, Leger, Raymond J. St., additional, Steele, James L., additional, Steinkühler, Christian, additional, Stenberg, Leisa M., additional, Stenflo, Johan, additional, Stennicke, Henning R., additional, Stepanov (Deceased), Valentin M., additional, Steven, Frank, additional, Stevenson, Kenneth J., additional, Stewart, David J., additional, Storer, Andrew C., additional, Stover, Cordula, additional, Sträter, Norbert, additional, Strauss, Ellen G., additional, Strauss, James H., additional, Stöcker, Walter, additional, Stříšovský, Kvido, additional, Suárez-Rendueles, Paz, additional, Sugimoto, Manabu, additional, Sulea, Traian, additional, Suzuki, Fumiaki, additional, Suzuki, Hideyuki, additional, Swenson, Stephen, additional, Szecsi, Pal B., additional, Szilágyi, László, additional, Taha, Muhamed-Kheir, additional, Takahashi, Kenji, additional, Takio, Koji, additional, Tamura, Tomohiro, additional, Tan, Fulong, additional, Hong Tan, Nget, additional, Tanase, Carmen, additional, Tang, Jordan, additional, Tanizaki, Martha M., additional, Tannich, Egbert, additional, Tans, G., additional, Tarentino (Deceased), Anthony L., additional, Tatnell, Peter J., additional, Tatsumi, Hiroki, additional, Tautz, Norbert, additional, Templin, Markus F., additional, Terada, Shigeyuki, additional, Thacker, C., additional, Theodoratou, Ekaterini, additional, Thiel, Heinz-Jürgen, additional, Thielens, Nicole M., additional, Thierry, Gonzales, additional, Thomas, Mark D., additional, Thornberry, Nancy A., additional, Thorsness, Mary K., additional, Thorsness, Peter E., additional, Tigue, Natalie J., additional, Tjalsma, Harold, additional, Tomkinson, Birgitta, additional, Tonello, Fiorella, additional, Toogood, H.S., additional, Toombs, Christopher, additional, Tortora, Paolo, additional, Tözsér, József, additional, Travis, James, additional, Tschesche, Harald, additional, Tsujimoto, Masafumi, additional, Tsunasawa, Susumu, additional, Tsu, Christopher A., additional, Tu, Anthony T., additional, Turk, Boris, additional, Turk, Dusan, additional, Turk, Vito, additional, Turner, Anthony J., additional, Uchikoba, Tetsuya, additional, Uitto, Veli-Jukka, additional, Ullmann, Dirk, additional, Valdenaire, Olivier, additional, Van Beeumen, Jozef, additional, Van de Ven, Wim J.M., additional, van den Burg, Bertus, additional, Maarten van Dijl, Jan, additional, van Roosmalen, Maarten L., additional, Van Wart, Harold E., additional, Vanoni, Marco, additional, Vath, Gregory M., additional, Velasco, Gloria, additional, Vendrell, Josep, additional, Venekei, István, additional, Vera, Pablo, additional, Verchot-Lubicz, Jeanmarie, additional, Vines, Richard R., additional, Volanakis, John E., additional, Wagner, Fred W., additional, Wainwright, Shane W., additional, Walker, Kenneth W., additional, Walker, Stephen J., additional, Wallach, Jean, additional, Walling, Linda L., additional, Walsh, Peter N., additional, Wang, P., additional, May Wang, Q., additional, Wassenaar, Alfred L.M., additional, Watts, Aaron B., additional, Weber, Joseph M., additional, Webster, Daniel R., additional, Weiss, Stephen J., additional, Wells, James A., additional, Wenzel, Herbert, additional, Wewer, Ulla M., additional, White, Judith M., additional, Wilk, Sherwin, additional, Wilkin, Jean-Marc, additional, Wilkins, Tracy D., additional, Wilkinson, Keith D., additional, Winther, Jakob R., additional, Wlodawer, Alexander, additional, Fred Woessner, J., additional, Wolfe, Michael S., additional, Wolfsberg, Tyra G., additional, Woodgate, Roger, additional, Wright, G.D., additional, Wu, Qingyu, additional, Xie, Sancai, additional, Yamagami, Kenjiro, additional, Yamaguchi, Nozomi, additional, Yamakawa, Yoshio, additional, Yamamoto, Kei, additional, Yamamoto, Shigeo, additional, Yana, Ikuo, additional, Yang, Maozhou, additional, Yasuda, Noriko, additional, Yasuhara, Toshimasa, additional, Yasumasu, Shigeki, additional, Yi, Elizabeth, additional, Yiallouros, Irene, additional, Yonezawa, Hiroo, additional, Ji Yoo, Soon, additional, Yoshimoto, Tadashi, additional, Young, Michael W., additional, Young, Stephen G., additional, Zavalova, Ludmila L., additional, Zdanov, Alexander, additional, and Zhang, Hong-Zhong, additional

Published
2004
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42. In Epigenomic Studies, Including Cell-Type Adjustments in Regression Models Can Introduce Multicollinearity, Resulting in Apparent Reversal of Direction of Association

Author

Barton, Sheila J., primary, Melton, Phillip E., additional, Titcombe, Philip, additional, Murray, Robert, additional, Rauschert, Sebastian, additional, Lillycrop, Karen A., additional, Huang, Rae-Chi, additional, Holbrook, Joanna D., additional, and Godfrey, Keith M., additional

Published
2019
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43. Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk

Author

Rauschert, Sebastian, primary, Melton, Phillip E., additional, Burdge, Graham, additional, Craig, Jeffrey M., additional, Godfrey, Keith M., additional, Holbrook, Joanna D., additional, Lillycrop, Karen, additional, Mori, Trevor A., additional, Beilin, Lawrence J., additional, Oddy, Wendy H., additional, Pennell, Craig, additional, and Huang, Rae-Chi, additional

Published
2019
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44. Neonatal amygdalae and hippocampi are influenced by genotype and prenatal environment, and reflected in the neonatal DNA methylome

Author

Ong, Mei‐Lyn, primary, Tuan, Ta A., additional, Poh, Joann, additional, Teh, Ai L., additional, Chen, Li, additional, Pan, Hong, additional, MacIsaac, Julia L., additional, Kobor, Michael S., additional, Chong, Yap S., additional, Kwek, Kenneth, additional, Saw, Seang M., additional, Godfrey, Keith M., additional, Gluckman, Peter D., additional, Fortier, Marielle V., additional, Karnani, Neerja, additional, Meaney, Michael J., additional, Qiu, Anqi, additional, and Holbrook, Joanna D., additional

Published
2019
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45. Epigenetic Age Acceleration in Adolescence Associates With BMI, Inflammation, and Risk Score for Middle Age Cardiovascular Disease

Author

Huang, Rae-Chi, primary, Lillycrop, Karen A, additional, Beilin, Lawrence J, additional, Godfrey, Keith M, additional, Anderson, Denise, additional, Mori, Trevor A, additional, Rauschert, Sebastian, additional, Craig, Jeffrey M, additional, Oddy, Wendy H, additional, Ayonrinde, Oyekoya T, additional, Pennell, Craig E, additional, Holbrook, Joanna D, additional, and Melton, Phillip E, additional

Published
2019
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46. Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

Author

Halsey Wendy S, Gallagher Kathleen T, Parker Joel S, Holbrook Joanna D, Hughes Ashley M, Weigman Victor J, Lebowitz Peter F, and Kumar Rakesh

Subjects
Medicine
Abstract

Abstract Background Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries. Methods Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers. Results Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways. Conclusions The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.

Published
2011
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48. The role of positive selection in determining the molecular cause of species differences in disease

Author

Foord Steven M, Simmons Mark D, Word Michael, Kumar Vinod, Topp Simon D, Rajagopalan Dilip, Amrine-Madsen Heather, Emes Richard D, Hasan Samiul, Vamathevan Jessica J, Sanseau Philippe, Yang Ziheng, and Holbrook Joanna D

Subjects
Evolution, QH359-425
Abstract

Abstract Background Related species, such as humans and chimpanzees, often experience the same disease with varying degrees of pathology, as seen in the cases of Alzheimer's disease, or differing symptomatology as in AIDS. Furthermore, certain diseases such as schizophrenia, epithelial cancers and autoimmune disorders are far more frequent in humans than in other species for reasons not associated with lifestyle. Genes that have undergone positive selection during species evolution are indicative of functional adaptations that drive species differences. Thus we investigate whether biomedical disease differences between species can be attributed to positively selected genes. Results We identified genes that putatively underwent positive selection during the evolution of humans and four mammals which are often used to model human diseases (mouse, rat, chimpanzee and dog). We show that genes predicted to have been subject to positive selection pressure during human evolution are implicated in diseases such as epithelial cancers, schizophrenia, autoimmune diseases and Alzheimer's disease, all of which differ in prevalence and symptomatology between humans and their mammalian relatives. In agreement with previous studies, the chimpanzee lineage was found to have more genes under positive selection than any of the other lineages. In addition, we found new evidence to support the hypothesis that genes that have undergone positive selection tend to interact with each other. This is the first such evidence to be detected widely among mammalian genes and may be important in identifying molecular pathways causative of species differences. Conclusion Our dataset of genes predicted to have been subject to positive selection in five species serves as an informative resource that can be consulted prior to selecting appropriate animal models during drug target validation. We conclude that studying the evolution of functional and biomedical disease differences between species is an important way to gain insight into their molecular causes and may provide a method to predict when animal models do not mirror human biology.

Published
2008
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49. Epigenetic age acceleration in adolescence associates with BMI, inflammation, and risk score for middle age cardiovascular disease

Author

Huang, Rae-Chi, Lillycrop, Karen A, Beilin, Lawrence J, Godfrey, Keith M, Anderson, Denise, Mori, Trevor A, Rauschert, Sebastian, Craig, Jeffrey M, Oddy, Wendy H, Ayonrinde, Oyekoya T, Pennell, Craig E, Holbrook, Joanna D, Melton, Phillip E, Huang, Rae-Chi, Lillycrop, Karen A, Beilin, Lawrence J, Godfrey, Keith M, Anderson, Denise, Mori, Trevor A, Rauschert, Sebastian, Craig, Jeffrey M, Oddy, Wendy H, Ayonrinde, Oyekoya T, Pennell, Craig E, Holbrook, Joanna D, and Melton, Phillip E

Abstract

Accelerated aging, assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age. Design: DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors [lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers] were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development.

Published
2019

50. Maternal smoking during pregnancy induces persistent epigenetic changes into adolescence, independent of postnatal smoke exposure and is associated with cardiometabolic risk

Author

Rauschert, Sebastian, Melton, Phillip E., Burdge, Graham, Craig, Jeffrey M., Godfrey, Keith M., Holbrook, Joanna D., Lillycrop, Karen, Mori, Trevor A., Beilin, Lawrence J., Oddy, Wendy H., Pennell, Craig, Huang, Rae-Chi, Rauschert, Sebastian, Melton, Phillip E., Burdge, Graham, Craig, Jeffrey M., Godfrey, Keith M., Holbrook, Joanna D., Lillycrop, Karen, Mori, Trevor A., Beilin, Lawrence J., Oddy, Wendy H., Pennell, Craig, and Huang, Rae-Chi

Abstract

© 2019 Rauschert, Melton, Burdge, Craig, Godfrey, Holbrook, Lillycrop, Mori, Beilin, Pennell and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Background Several studies have shown effects of current and maternal smoking during pregnancy on DNA methylation of CpG sites in newborns and later in life. Here we hypothesized that there are long-term and persistent epigenetic effects following maternal smoking during pregnancy on adolescent offspring DNA methylation, independent of paternal and postnatal smoke exposure. Further, we explored the association between DNA methylation and cardiometabolic risk factors at 17 years of age. Materials and Methods DNA methylation was measured using the Illumina HumanMethylation450K BeadChip in whole blood from 995 participants attending the 17-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study. Linear mixed effects models were used to identify differential methylated CpGs, adjusting for parental smoking during pregnancy, and paternal, passive and adolescent smoke exposure. Additional models examined the association between DNA methylation and paternal, adolescent and passive smoking over the life-course. Offspring CpGs identified were analysed against cardiometabolic risk factors (blood pressure, triacylglycerols (TG), high-density lipoproteins cholesterol (HDL-C) and body mass index). Results We identified 23 CpGs (genome wide p-level: 1.06 × 10-7), that were associated with maternal smoking during pregnancy, including associated genes AHRR (cancer development), FTO (obesity), CNTNAP2 (developmental processes)

Published
2019

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