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Sökning: onr:"swepub:oai:DiVA.org:uu-212866" > Global Analysis of ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003811naa a2200529 4500
001oai:DiVA.org:uu-212866
003SwePub
008131216s2013 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2128662 URI
0247 a https://doi.org/10.1016/j.ajhg.2013.10.0042 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Grundberg, Elin4 aut
2451 0a Global Analysis of DNA Methylation Variation in Adipose Tissue from Twins Reveals Links to Disease-Associated Variants in Distal Regulatory Elements
264 1b Elsevier BV,c 2013
338 a print2 rdacarrier
520 a Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Human Expression Resource (MuTHER) and generated Illumina 450K adipose methylome data from 648 twins. We found that individual CpGs had low variance and that variability was suppressed in promoters. We noted that DNA methylation variation was highly heritable (h(median)(2) = 0.34) and that shared environmental effects correlated with metabolic phenotype-associated CpGs. Analysis of methylation quantitative-trait loci (metQTL) revealed that 28% of CpGs were associated with nearby SNPs, and when overlapping them with adipose expression quantitative-trait loci (eQTL) from the same individuals, we found that 6% of the loci played a role in regulating both gene expression and DNA methylation. These associations were bidirectional, but there were pronounced negative associations for promoter CpGs. Integration of metQTL with adipose reference epigenomes and disease associations revealed significant enrichment of metQTL overlapping metabolic-trait or disease loci in enhancers (the strongest effects were for high-density lipoprotein cholesterol and body mass index [BMI]). We followed up with the BMI SNP rs713586, a cg01884057 metQTL that overlaps an enhancer upstream of ADCY3, and used bisulphite sequencing to refine this region. Our results showed widespread population invariability yet sequence dependence on adipose DNA methylation but that incorporating maps of regulatory elements aid in linking CpG variation to gene regulation and disease risk in a tissue-dependent manner.
7001 a Meduri, Eshwar4 aut
7001 a Sandling, Johanna K.u Uppsala universitet,Molekylär medicin4 aut0 (Swepub:uu)josan062
7001 a Hedman, Asa K.4 aut
7001 a Keildson, Sarah4 aut
7001 a Buil, Alfonso4 aut
7001 a Busche, Stephan4 aut
7001 a Yuan, Wei4 aut
7001 a Nisbet, James4 aut
7001 a Sekowska, Magdalena4 aut
7001 a Wilk, Alicja4 aut
7001 a Barrett, Amy4 aut
7001 a Small, Kerrin S.4 aut
7001 a Ge, Bing4 aut
7001 a Caron, Maxime4 aut
7001 a Shin, So-Youn4 aut
7001 a Lathrop, Mark4 aut
7001 a Dermitzakis, Emmanouil T.4 aut
7001 a McCarthy, Mark I.4 aut
7001 a Spector, Timothy D.4 aut
7001 a Bell, Jordana T.4 aut
7001 a Deloukas, Panos4 aut
7102 a Uppsala universitetb Molekylär medicin4 org
7730 t American Journal of Human Geneticsd : Elsevier BVg 93:5, s. 876-890q 93:5<876-890x 0002-9297x 1537-6605
8564 u https://doi.org/10.1016/j.ajhg.2013.10.004y Fulltext
8564 u http://www.cell.com/article/S0002929713004618/pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-212866
8564 8u https://doi.org/10.1016/j.ajhg.2013.10.004

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