The Presence of Methylation Quantitative Trait Loci Indicates a Direct Genetic Influence on the Level of DNA Methylation in Adipose Tissue

Drong, Alexander W.; Nicholson, George; Hedman, Åsa K.; Meduri, Eshwar; Grundberg, Elin; Small, Kerrin S.; Shin, So–Youn; Bell, Jordana T.; Karpe, Fredrik; Soranzo, Nicole; Spector, Tim D.; McCarthy, Mark I.; Deloukas, Panos; Rantalainen, Mattias; Lindgren, Cecilia M.

doi:10.1371/journal.pone.0055923

Cited by 79 publications

(65 citation statements)

References 41 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…meQTLs, and mediators such as DNA binding factors or secondary chromatin structures, are thought to be the functional link between the genetic sequence and the differential methylation. 27,28 In the case of ARMS2, the lower methylation level of chr10:124214120 in the blood correlated with the risk allele, T, at rs10490924, whereas in the retina of AMD patients, the risk allele significantly associated with the methylation level of chr10:124213466, possibly reflecting either true tissue-specific differences or the result of a much smaller retinal sample size.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential DNA methylation identified in the blood and retina of AMD patients

Oliver¹,

Jaffe

Song

et al. 2015

Epigenetics

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a major cause of blindness in the western world. While genetic studies have linked both common and rare variants in genes involved in regulation of the complement system to increased risk of development of AMD, environmental factors, such as smoking and nutrition, can also significantly affect the risk of developing the disease and the rate of disease progression. Since epigenetics has been implicated in mediating, in part, the disease risk associated with some environmental factors, we investigated a possible epigenetic contribution to AMD. We performed genome-wide DNA methylation profiling of blood from AMD patients and controls. No differential methylation site reached genome-wide significance; however, when epigenetic changes in and around known GWASdefined AMD risk loci were explored, we found small but significant DNA methylation differences in the blood of neovascular AMD patients near age-related maculopathy susceptibility 2 (ARMS2), a top-ranked GWAS locus preferentially associated with neovascular AMD. The methylation level of one of the CpG sites significantly correlated with the genotype of the risk SNP rs10490924, suggesting a possible epigenetic mechanism of risk. Integrating genome-wide DNA methylation analysis of retina samples with and without AMD together with blood samples, we further identified a consistent, replicable change in DNA methylation in the promoter region of protease serine 50 (PRSS50). These methylation changes may identify sites in novel genes that are susceptible to non-genetic factors known to contribute to AMD development and progression.

show abstract

Section: Discussionmentioning

confidence: 99%

“…We further adjusted for estimated surrogate variables estimated from each model (blood: 47 for all, 32 for NV, and 35 for GA; eye: 5) to control for potential unmeasured technical and/or biological confounding, 28,29 including cellular composition of blood. 26,30 See Jaffe et al, 2012 for additional details on this statistical framework.…”

Section: Discussionmentioning

confidence: 99%

Differential DNA methylation identified in the blood and retina of AMD patients

Oliver¹,

Jaffe

Song

et al. 2015

Epigenetics

View full text Add to dashboard Cite

show abstract

“…13 Several genome-wide association studies with methylation quantitative trait loci (mQTL) in both cis and trans locations have confirmed the genetic heritability of DNA methylation. 14,17,18 However, it is difficult to understand to what extent the observed familial resemblance in DNA methylation is due to genetic heritability and/or common environmental effect.…”

Section: Introductionmentioning

confidence: 99%

Familial resemblances in blood leukocyte DNA methylation levels

et al. 2016

View full text Add to dashboard Cite

show abstract

“…For example, it is easier to avoid the influence of DNA sequence (genetics) on DNA methylation when the samples come from the same individual. 46,47 However, the issues of tissue relevance and cell composition heterogeneity are still pertinent.…”

Section: Tissuementioning

confidence: 99%