DNA methylation profiles in monozygotic and dizygotic twins

• Published in: Nature genetics Vol. 41; no. 2; pp. 240 - 245
• Main Authors: Kaminsky, Zachary A, Tang, Thomas, Wang, Sun-Chong, Ptak, Carolyn, Oh, Gabriel H T, Wong, Albert H C, Feldcamp, Laura A, Virtanen, Carl, Halfvarson, Jonas, Tysk, Curt, McRae, Allan F, Visscher, Peter M, Montgomery, Grant W, Gottesman, Irving I, Martin, Nicholas G, Petronis, Art
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2009; Nature Publishing Group
• Subjects: Adolescent; Agriculture; Animal Genetics and Genomics; Animals; Animals, Outbred Strains; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood transfusions; Cancer Research; Case-Control Studies; Child; Chromosome Mapping; CpG Islands; Deoxyribonucleic acid; DNA; DNA Methylation - physiology; DNA microarrays; Epithelial Cells - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Function; Genetic aspects; Genetic testing; Genetics of eukaryotes. Biological and molecular evolution; Health aspects; Human Genetics; Humans; letter; Leukocytes - metabolism; Male; Medicin; Medicine; Mental health; Methylation; Mice; Mice, Inbred Strains; Mouth Mucosa - metabolism; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; Studies; Tissues; Twin studies; Twins; Twins, Dizygotic - genetics; Twins, Monozygotic - genetics; Canada; United States; Methylation; Monozygotic twin; DNA; Dizygotic twin
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.286

Arturas Petronis and colleagues present the first genome-wide study of interindividual differences in DNA methylation through genome-scale DNA methylation profiling in tissues from monozygotic and dizygotic twins. The data showed that dizygotic co-twins have higher degrees of epigenetic differences than monozygotic co-twins, which the authors attribute at least partially to epigenetic, as opposed to genetic, differences in the zygotes. Twin studies have provided the basis for genetic and epidemiological studies in human complex traits 1 , 2 . As epigenetic factors can contribute to phenotypic outcomes, we conducted a DNA methylation analysis in white blood cells (WBC), buccal epithelial cells and gut biopsies of 114 monozygotic (MZ) twins as well as WBC and buccal epithelial cells of 80 dizygotic (DZ) twins using 12K CpG island microarrays 3 , 4 . Here we provide the first annotation of epigenetic metastability of ∼6,000 unique genomic regions in MZ twins. An intraclass correlation (ICC)-based comparison of matched MZ and DZ twins showed significantly higher epigenetic difference in buccal cells of DZ co-twins ( P = 1.2 × 10 −294 ). Although such higher epigenetic discordance in DZ twins can result from DNA sequence differences, our in silico SNP analyses and animal studies favor the hypothesis that it is due to epigenomic differences in the zygotes, suggesting that molecular mechanisms of heritability may not be limited to DNA sequence differences.