The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood
Open accessAbstract
Inter-individual DNA methylation variations were frequently hypothesized to alter individual susceptibility to Type 2 Diabetes Mellitus (T2DM). Sequence-influenced methylations were described in T2DM-associated genomic regions, but evidence for direct, sequence-independent association with disease risk is missing. Here, we explore disease-contributing DNA methylation through a stepwise study design: first, a pool-based, genome-scale screen among 1169 case and control individuals revealed an excess of differentially methylated sites in genomic regions that were previously associated with T2DM through genetic studies. Next, in-depth analyses were performed at selected top-ranking regions. A CpG site in the first intron of the FTO gene showed small (3.35%) but significant (P = 0.000021) hypomethylation of cases relative to controls. The effect was independent of the sequence polymorphism in the region and persists among individuals carrying the sequence-risk alleles. The odds of belonging to the T2DM group increased by 6.1% for every 1% decrease in methylation (OR = 1.061, 95% CI: 1.032-1.090), the odds ratio for decrease of 1 standard deviation of methylation (adjusted to gender) was 1.5856 (95% CI: 1.2824-1.9606) and the sensitivity (area under the curve = 0.638, 95% CI: 0.586-0.690; males = 0.675, females = 0.609) was better than that of the strongest known sequence variant. Furthermore, a prospective study in an independent population cohort revealed significant hypomethylation of young individuals that later progressed to T2DM, relative to the individuals who stayed healthy. Further genomic analysis revealed co-localization with gene enhancers and with binding sites for methylation-sensitive transcriptional regulators. The data showed that low methylation level at the analyzed sites is an early marker of T2DM and suggests a novel mechanism by which early-onset, inter-individual methylation variation at isolated non-promoter genomic sites predisposes to T2DM.
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877
Human DNA methylomes at base resolution show widespread epigenomic differences
Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., Nery, J. R., Lee, L., Ye, Z., Ngo, Q.-M., et al. (2009) · Nature · doi:10.1038/nature08514 · Cited by 4,673
Frayling, T. M., Timpson, N. J., Weedon, M. N., Zeggini, E., Freathy, R. M., Lindgren, C. M., Perry, J. R. B., Elliott, K. S., Lango, H., Rayner, N. W., et al. (2007) · Science · doi:10.1126/science.1141634 · Cited by 4,531
A second generation human haplotype map of over 3.1 million SNPs
The International HapMap Consortium (2007) · Nature · doi:10.1038/nature06258 · Cited by 4,438
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129
Genome-Wide Mapping of in Vivo Protein-DNA Interactions
Johnson, D. S., Mortazavi, A., Myers, R. M., & Wold, B. (2007) · Science · doi:10.1126/science.1141319 · Cited by 2,927
Epigenetic modifications and human disease
Portela, A., & Esteller, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1685 · Cited by 2,836
Linking DNA methylation and histone modification: patterns and paradigms
Cedar, H., & Bergman, Y. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2540 · Cited by 2,267 · cited 1×
“DNA methylation levels are generally established early in development and are stably maintained thereafter (34).”
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Cited by
Reinius, L. E., Acevedo, N., Joerink, M., Pershagen, G., Dahlén, S.-E., Greco, D., Söderhäll, C., Scheynius, A., & Kere, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041361 · Cited by 1,035
Dayeh, T., Volkov, P., Salö, S., Hall, E., Nilsson, E., Olsson, A. H., Kirkpatrick, C. L., Wollheim, C. B., Eliasson, L., Rönn, T., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004160 · Cited by 523
Touleimat, N., & Tost, J. (2012) · Epigenomics · doi:10.2217/epi.12.21 · Cited by 507
Lehne, B., Drong, A. W., Loh, M., Zhang, W., Scott, W. R., Tan, S.-T., Afzal, U., Scott, J., Jarvelin, M.-R., Elliott, P., et al. (2015) · Genome biology · doi:10.1186/s13059-015-0600-x · Cited by 380
Demerath, E. W., Guan, W., Grove, M. L., Aslibekyan, S., Mendelson, M., Zhou, Y.-H., Hedman, Å. K., Sandling, J. K., Li, L.-A., Irvin, M. R., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv161 · Cited by 355
Metadata
- Authors
- Toperoff, G., Aran, D., Kark, J. D., Rosenberg, M., Dubnikov, T., Nissan, B., Wainstein, J., Friedlander, Y., Levy-Lahad, E., Glaser, B., & Hellman, A.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-10-12
- Volume
- 21
- Issue
- 2
- Pages
- 371-383
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2103714979
- Cited by
- 349
- References
- 45
- FWCI
- 12.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Toperoff, G., Aran, D., Kark, J. D., Rosenberg, M., Dubnikov, T., Nissan, B., Wainstein, J., Friedlander, Y., Levy-Lahad, E., Glaser, B., & Hellman, A. (2012). Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddr472
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