DNA methylation profiles in monozygotic and dizygotic twins.
Twin studies have provided the basis for genetic and epidemiological studies in human complex traits. 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. Here we provide the first annotation of epigenetic metastability of approximately 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 x 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.
Kaminsky
Zachary A
ZA
Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada.
Tang
Thomas
T
Wang
Sun-Chong
SC
Ptak
Carolyn
C
Oh
Gabriel H T
GH
Wong
Albert H C
AH
Feldcamp
Laura A
LA
Virtanen
Carl
C
Halfvarson
Jonas
J
Tysk
Curt
C
McRae
Allan F
AF
Visscher
Peter M
PM
Montgomery
Grant W
GW
Gottesman
Irving I
II
Martin
Nicholas G
NG
Petronis
Art
A
D000293:Adolescent; D000818:Animals; D021461:Animals, Outbred Strains; D016022:Case-Control Studies; D002648:Child; D002874:Chromosome Mapping; D018899:CpG Islands; D019175:DNA Methylation / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009061:Mouth Mucosa / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*