A twin approach to unraveling epigenetics.
The regulation of gene expression plays a pivotal role in complex phenotypes, and epigenetic mechanisms such as DNA methylation are essential to this process. The availability of next-generation sequencing technologies allows us to study epigenetic variation at an unprecedented level of resolution. Even so, our understanding of the underlying sources of epigenetic variability remains limited. Twin studies have played an essential role in estimating phenotypic heritability, and these now offer an opportunity to study epigenetic variation as a dynamic quantitative trait. High monozygotic twin discordance rates for common diseases suggest that unexplained environmental or epigenetic factors could be involved. Recent genome-wide epigenetic studies in disease-discordant monozygotic twins emphasize the power of this design to successfully identify epigenetic changes associated with complex traits. We describe how large-scale epigenetic studies of twins can improve our understanding of how genetic, environmental and stochastic factors impact upon epigenetics, and how such studies can provide a comprehensive understanding of how epigenetic variation affects complex traits.
Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK. jordana@well.ox.ac.uk
Jordana T
JT
Bell
Tim D
TD
Spector
D004777:Environment; D057890:Epigenomics / Q000379:methods / Q000639:trends; D014644:Genetic Variation; D006801:Humans; D010641:Phenotype; D018433:Twin Studies as Topic; D014427:Twins / Q000235:genetics* / Q000378:metabolism
Genetics. 2009 Jul;182(3):845-50
19416939
J Am Coll Radiol. 2005 Jun;2(6):478-84
17411863
Curr Opin Genet Dev. 2005 Oct;15(5):490-5
16098738
Genes Dev. 2002 Jan 1;16(1):6-21
11782440
Genome Res. 2010 Apr;20(4):440-6
20219944
Ann Rheum Dis. 2005 Feb;64(2):309-10
15231511
Am J Hum Genet. 2010 Mar 12;86(3):411-9
20215007
Lab Anim. 1990 Jan;24(1):71-7
2406501
Science. 2010 Apr 9;328(5975):235-9
20299549
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8252-6
2236038
Nat Rev Genet. 2009 May;10(5):295-304
19308066
Ann N Y Acad Sci. 2010 Mar;1192:181-9
20392235
Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141B(4):421-5
16583437
Hum Mol Genet. 2010 Nov 1;19(21):4176-88
20699328
Am J Hum Genet. 2010 Feb 12;86(2):196-212
20159110
Am J Hum Genet. 1990 Feb;46(2):222-8
2301392
Transpl Immunol. 2010 Jul;23(3):104-10
20471480
Cytogenet Cell Genet. 1975;14(1):9-25
1093816
Nat Genet. 2006 Nov;38(11):1348-54
17033623
Arthritis Rheum. 2000 Jan;43(1):30-7
10643697
Nat Rev Genet. 2006 May;7(5):395-401
16534512
Aging Cell. 2006 Oct;5(5):361-5
16856882
Science. 2009 May 15;324(5929):929-30
19372393
Arthritis Rheum. 1996 May;39(5):732-5
8639169
Am J Hum Genet. 1990 Feb;46(2):229-41
2301393
Am J Hum Genet. 1991 May;48(5):873-9
2018039
Heredity (Edinb). 2010 Jul;105(1):92-104
20442734
Science. 2001 Aug 10;293(5532):1068-70
11498573
Nat Genet. 2004 Aug;36(8):889-93
15273689
J Cell Physiol. 2010 Mar;222(3):522-31
20020444
Nat Genet. 2005 Aug;37(8):853-62
16007088
Hum Mol Genet. 2004 Jan 15;13(2):247-55
14645199
Hum Mol Genet. 2007 Mar 1;16(5):547-54
17339271
Nat Genet. 2009 Feb;41(2):178-186
19151715
Nat Biotechnol. 2010 Oct;28(10):1106-14
20852634
Nat Biotechnol. 2010 Oct;28(10):1097-105
20852635
Nature. 2007 May 24;447(7143):425-32
17522676
Science. 1975 Jan 24;187(4173):226-32
1111098
Nat Genet. 2004 May;36(5):497-501
15064764
Nat Genet. 2008 Jul;40(7):904-8
18568024
Blood. 2001 Mar 1;97(5):1274-81
11222370
Twin Res. 2001 Oct;4(5):307-17
11869481
PLoS One. 2009 Aug 26;4(8):e6767
19774229
Nat Rev Genet. 2008 Apr;9(4):255-66
18319743
Trends Biochem Sci. 2006 Feb;31(2):89-97
16403636
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2538-43
12601169
Am J Hum Genet. 2004 Apr;74(4):599-609
14991528
Am J Hum Genet. 1990 Feb;46(2):242-53
2301394
Arch Gen Psychiatry. 1999 Jan;56(1):39-44
9892254
Nat Genet. 2009 Dec;41(12):1350-3
19881528
Hum Mol Genet. 2002 May 15;11(11):1317-25
12019213
Nat Neurosci. 2008 Sep;11(9):1024-34
19160500
BMJ. 1995 Jul 15;311(6998):171-4
7613432
Mutat Res. 2008 Dec 1;647(1-2):30-8
18778722
N Engl J Med. 1994 Feb 10;330(6):387-92
8284003
Arch Gen Psychiatry. 2003 Dec;60(12):1187-92
14662550
PLoS Genet. 2010 May 13;6(5):e1000952
20485568
Nat Rev Cancer. 2003 Apr;3(4):253-66
12671664
Genome Res. 2010 Apr;20(4):434-9
20219945
Genome Res. 2009 Jun;19(6):959-66
19273618
FASEB J. 2010 Sep;24(9):3135-44
20385621
Hum Mol Genet. 2008 Oct 15;17(R2):R156-65
18852205
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
16009939
Nat Genet. 2009 Feb;41(2):240-5
19151718
Nature. 2010 Jun 10;465(7299):721-7
20535201
Genome Res. 2006 Oct;16(10):1299-309
16954542
Nat Genet. 2003 Mar;33 Suppl:245-54
12610534
Am J Hum Genet. 2006 Jul;79(1):155-62
16773576
JAMA. 2008 Jun 25;299(24):2877-83
18577732
Nat Rev Genet. 2008 Nov;9(11):883-90
18927581
Annu Rev Genomics Hum Genet. 2008;9:233-57
18767965
Mol Psychiatry. 2008 Apr;13(4):429-41
17471289
Nat Cell Biol. 2006 Feb;8(2):188-94
16415856
Genome Res. 2010 Feb;20(2):170-9
20028698
Epigenetics. 2010 Aug 16;5(6):516-26
20505345
Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5802-7
15827124
Circulation. 2004 Jun 22;109(24):3022-8
15184288
Nat Biotechnol. 2008 Jul;26(7):779-85
18612301
PLoS Genet. 2009 Jun;5(6):e1000530
19557164
MMWR Surveill Summ. 2003 Aug 29;52(9):1-16
14532867
Science. 2010 Apr 9;328(5975):232-5
20299548
Nat Methods. 2010 Jun;7(6):461-5
20453866
Nat Genet. 2010 Mar;42(3):255-9
20118932
Nature. 2007 May 24;447(7143):433-40
17522677
Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14926-31
19706456
Twin Res Hum Genet. 2008 Feb;11(1):1-11
18251670
Genome Res. 2008 Jul;18(7):1171-9
18502945
Science. 2002 Feb 15;295(5558):1306-11
11847345
BMJ. 1996 Apr 13;312(7036):940-3
8616305
Nature. 2010 Apr 29;464(7293):1351-6
20428171
Nature. 2009 Oct 8;461(7265):747-53
19812666
Nucleic Acids Res. 2006 Jan 20;34(2):528-42
16428248
Nature. 1981 Aug 13;292(5824):646-7
7254360
Trends Genet. 2004 Mar;20(3):113-6
15049300
Schizophr Bull. 2003;29(1):169-78
12908672
Nat Genet. 2006 Dec;38(12):1378-85
17072317
Nat Biotechnol. 2009 Apr;27(4):361-8
19329998
Dev Genet. 1994;15(6):453-7
7834903
Nat Rev Genet. 2011 Jan;12(1):7-18
21116306
Proc Natl Acad Sci U S A. 1987 Sep;84(17):6210-4
3476942
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5237-42
10805783
Trends Genet. 2000 Mar;16(3):131-4
10689354
Oncogene. 2002 Aug 12;21(35):5361-79
12154399
Annu Rev Biochem. 2005;74:481-514
15952895
Cell. 2008 Jan 25;132(2):311-22
18243105