Browsing by Author "Mill, Jonathan"
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Item Open Access A longitudinal study of epigenetic variation in twins.(Epigenetics, 2010-08-16) Wong, Chloe Chung Yi; Caspi, Avshalom; Williams, Benjamin; Craig, Ian W; Houts, Renate; Ambler, Antony; Moffitt, Terrie E; Mill, JonathanDNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. Alterations in DNA methylation are established contributors to inter-individual phenotypic variation and have been associated with disease susceptibility. The degree to which changes in loci-specific DNA methylation are under the influence of heritable and environmental factors is largely unknown. In this study, we quantitatively measured DNA methylation across the promoter regions of the dopamine receptor 4 gene (DRD4), the serotonin transporter gene (SLC6A4/SERT) and the X-linked monoamine oxidase A gene (MAOA) using DNA sampled at both ages 5 and 10 years in 46 MZ twin-pairs and 45 DZ twin-pairs (total n=182). Our data suggest that DNA methylation differences are apparent already in early childhood, even between genetically identical individuals, and that individual differences in methylation are not stable over time. Our longitudinal-developmental study suggests that environmental influences are important factors accounting for interindividual DNA methylation differences, and that these influences differ across the genome. The observation of dynamic changes in DNA methylation over time highlights the importance of longitudinal research designs for epigenetic research.Item Open Access Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm.(eLife, 2020-05-05) Belsky, Daniel W; Caspi, Avshalom; Arseneault, Louise; Baccarelli, Andrea; Corcoran, David L; Gao, Xu; Hannon, Eiliss; Harrington, Hona Lee; Rasmussen, Line Jh; Houts, Renate; Huffman, Kim; Kraus, William E; Kwon, Dayoon; Mill, Jonathan; Pieper, Carl F; Prinz, Joseph A; Poulton, Richie; Schwartz, Joel; Sugden, Karen; Vokonas, Pantel; Williams, Benjamin S; Moffitt, Terrie EBiological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972-1973. Rates of change in each biomarker over ages 26-38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person's pace of biological aging.Item Open Access The PsychENCODE project.(Nat Neurosci, 2015-12) PsychENCODE Consortium; Akbarian, Schahram; Liu, Chunyu; Knowles, James A; Vaccarino, Flora M; Farnham, Peggy J; Crawford, Gregory E; Jaffe, Andrew E; Pinto, Dalila; Dracheva, Stella; Geschwind, Daniel H; Mill, Jonathan; Nairn, Angus C; Abyzov, Alexej; Pochareddy, Sirisha; Prabhakar, Shyam; Weissman, Sherman; Sullivan, Patrick F; State, Matthew W; Weng, Zhiping; Peters, Mette A; White, Kevin P; Gerstein, Mark B; Amiri, Anahita; Armoskus, Chris; Ashley-Koch, Allison E; Bae, Taejeong; Beckel-Mitchener, Andrea; Berman, Benjamin P; Coetzee, Gerhard A; Coppola, Gianfilippo; Francoeur, Nancy; Fromer, Menachem; Gao, Robert; Grennan, Kay; Herstein, Jennifer; Kavanagh, David H; Ivanov, Nikolay A; Jiang, Yan; Kitchen, Robert R; Kozlenkov, Alexey; Kundakovic, Marija; Li, Mingfeng; Li, Zhen; Liu, Shuang; Mangravite, Lara M; Mangravite, Lara M; Mattei, Eugenio; Markenscoff-Papadimitriou, Eirene; Navarro, Fábio CP; North, Nicole; Omberg, Larsson; Panchision, David; Parikshak, Neelroop; Poschmann, Jeremie; Price, Amanda J; Purcaro, Michael; Reddy, Timothy E; Roussos, Panos; Schreiner, Shannon; Scuderi, Soraya; Sebra, Robert; Shibata, Mikihito; Shieh, Annie W; Skarica, Mario; Sun, Wenjie; Swarup, Vivek; Thomas, Amber; Tsuji, Junko; van Bakel, Harm; Wang, Daifeng; Wang, Yongjun; Wang, Kai; Werling, Donna M; Willsey, A Jeremy; Witt, Heather; Won, Hyejung; Wong, Chloe CY; Wray, Gregory A; Wu, Emily Y; Xu, Xuming; Yao, Lijing; Senthil, Geetha; Lehner, Thomas; Sklar, Pamela; Sestan, Nenad