Methylation array data can simultaneously identify individuals and convey protected health information: an unrecognized ethical concern

BACKGROUND: Genome-wide methylation arrays are increasingly used tools in studies of complex medical disorders. Because of their expense and potential utility to the scientific community, current federal policy dictates that data from these arrays, like those from genome-wide genotyping arrays, be deposited in publicly available databases. Unlike the genotyping information, access to the expression data is not restricted. An underlying supposition in the current nonrestricted access to methylation data is the belief that protected health and personal identifying information cannot be simultaneously extracted from these arrays. RESULTS: In this communication, we analyze methylation data from the Illumina HumanMethylation450 array and show that genotype at 1,069 highly informative loci, and both alcohol and smoking consumption information, can be derived from the array data. CONCLUSIONS: We conclude that both potentially personally identifying information and substance-use histories can be simultaneously derived from methylation array data. Because access to genetic information about a database subject or one of their relatives is critical to the de-identification process, this risk of de-identification is limited at the current time. We propose that access to genome-wide methylation data be restricted to institutionally approved investigators who accede to data use agreements prohibiting re-identification

Effects of Genotype and Child Abuse on DNA Methylation and Gene Expression at the Serotonin Transporter

Altered regulation of the serotonin transporter (SLC6A4) is hypothesized to be a key event in many forms of neuropsychiatric illness, yet our understanding of the molecular mechanisms through which changes in gene function could lead to illness remains incomplete. In prior studies, we and others have demonstrated that methylation of CpG residues in the promoter associated CpG island alters SLC6A4 gene expression, that the extent of that DNA methylation in child abuse is genotype dependent, and that adverse childhood experiences such as child sex abuse are related to methylation. However, we have not examined whether these effects are splice variant specific, whether the association of methylation to gene expression varies as a function of genotype, and whether methylation in other SLC6A4 gene regions are more likely candidates for GxE effects. In the current investigation we measured methylation in lymphoblast DNA from 158 female subjects in the Iowa Adoption Studies at 16 CpG residues spread across the SLC6A4 locus, and analyzed their relationship to gene expression for two SLC6A4 splice variants. Methylation of two CpG residues in the shore of the CpG island (cg22584138 and cg05951817), a location immediately upstream from exon 1A, predicted gene expression for the splice variant containing Exon 1A + 1B. Methylation at two residues in the CpG island itself (cg 25769822 and cg05016953) was associated with total SLC6A4 expression. Examination of these four CpG residues indicated that methylation of cg22584138 was influenced by both genotype and sex abuse, whereas methylation of cg05016953 was influenced only by sex abuse history. Factors influencing methylation at other CpG dinucleotide pairs were not identified. We conclude that methylation effects on transcription may vary as a function of underlying gene motif and splice variant, and that the shore of CpG islands, upstream of TSS, may be of particular interest in examining environmental effects on methylation

Calibration of thickness-dependent k-factors for germanium X-ray lines to improve energy-dispersive X-ray spectroscopy of SiGe layers in analytical transmission electron microscopy

We show that the accuracy of energy-dispersive X-ray spectroscopy can be improved by analysing and comparing multiple lines from the same element. For each line, an effective k-factor can be defined that varies as a function of the intensity ratio of multiple lines (e.g. K/L) from the same element. This basically performs an internal self-consistency check in the quantification using differently absorbed X-ray lines, which is in principle equivalent to an absorption correction as a function of specimen thickness but has the practical advantage that the specimen thickness itself does not actually need to be measured

Diffusion and jump-length distribution in liquid and amorphous Cu33_{33}Zr67_{67}

Using molecular dynamics simulation, we calculate the distribution of atomic jum ps in Cu$_{33}$Zr$_{67}$ in the liquid and glassy states. In both states the distribution of jump lengths can be described by a temperature independent exponential of the length and an effective activation energy plus a contribution of elastic displacements at short distances. Upon cooling the contribution of shorter jumps dominates. No indication of an enhanced probability to jump over a nearest neighbor distance was found. We find a smooth transition from flow in the liquid to jumps in the g lass. The correlation factor of the diffusion constant decreases with decreasing temperature, causing a drop of diffusion below the Arrhenius value, despite an apparent Arrhenius law for the jump probability

Methylation Array Data Can Simultaneously Identify Individual and Convey Protected Health Information: an Unrecognized Ethical Concern

Background: Genome-wide methylation arrays are increasingly used tools in studies of complex medical disorders. Because of their expense and potential utility to the scientific community, current federal policy dictates that data from these arrays, like those from genome-wide genotyping arrays, be deposited in publicly available databases. Unlike the genotyping information, access to the expression data is not restricted. An underlying supposition in the current nonrestricted access to methylation data is the belief that protected health and personal identifying information cannot be simultaneously extracted from these arrays. Results: In this communication, we analyze methylation data from the Illumina HumanMethylation450 array and show that genotype at 1,069 highly informative loci, and both alcohol and smoking consumption information, can be derived from the array data. Conclusions: We conclude that both potentially personally identifying information and substance-use histories can be simultaneously derived from methylation array data. Because access to genetic information about a database subject or one of their relatives is critical to the de-identification process, this risk of de-identification is limited at the current time. We propose that access to genome-wide methylation data be restricted to institutionally approved investigators who accede to data use agreements prohibiting re-identification

Impact of child sex abuse on adult psychopathology: A genetically and epigenetically informed investigation

Genetic, environmental, and epigenetic influences and their transactions were examined in a sample of 155 women from the Iowa adoptee sample who had been removed from their biological parents shortly after birth and assessed when participants were an average of 41.10 years old. We observed an interactive effect of child sex abuse (CSA) and biological parent psychopathology (i.e., genetic load) on substance abuse as well as a main effect of CSA on substance abuse in adulthood. We also observed main effects of CSA and genetic load on depression and on antisocial characteristics. As predicted, CSA, but not genetic load or later substance abuse, was associated with epigenetic change. In addition, the interaction between genetic load and CSA predicted epigenetic change, indicating a potential genetic basis for a differential impact of CSA on epigenetic change. Finally, epigenetic change partially mediated the effect of CSA on antisocial characteristics. The results suggest the relevance of genetic and epigenetic processes for future theorizing regarding marital and family precursors of several forms of adult psychopathology. Implications for preventive intervention are discussed

Methylation of MTHFR Moderates the Effect of Smoking on Genomewide Methylation Among Middle Age African Americans

Differential methylation at MTHFR (mMTHFR) has been examined previously as a moderator of changes in methylation among nascent smokers, but the effects of mMTHFR on genomewide patterns of methylation among established smokers in middle age are unknown. In the current investigation we examined a sample of 180 African American middle-aged smokers and non-smokers to test for patterns indicative of three different potential mechanisms of impact on epigenetic remodeling in response to long-term smoking. We found that mMTHFR moderated the association between smoking and changes in methylation for more than 25% of the 909 loci previously identified as being associated with smoking at a genomewide level of significance in middle-aged African Americans. Observed patterns of effect indicated amplification of both hyper and hypo methylating responses to smoking among those with lower mMTHFR. Moderating effects were robust to controls for sex, age, diet, and cell-type variation. Implications for potential mechanisms conferring effects are discussed. Of particular potential practical importance was a strong effect of mMTHFR on hypomethylation at GPR15 in response to smoking, indicative of the differential impact of MTHFR activity on changes in a specific cell population linked to inflammatory disease in smokers

Self-organized transient facilitated atomic transport in Pt/Al(111)

During the course of atomic transport in a host material, impurity atoms need to surmount an energy barrier driven by thermodynamic bias or at ultra-low temperatures by quantum tunneling. In the present article we demonstrate using atomistic simulations that at ultra-low temperature transient inter-layer atomic transport is also possible without tunneling when the Pt/Al(111) impurity/host system self-organizes itself spontaneously into an intermixed configuration. No such extremely fast athermal concerted process has been reported before at ultra low temperatures. The outlined novel transient atomic exchange mechanism could be of general validity. We find that the source of ultra-low temperature heavy particle barrier crossing is intrinsic and no external bias is necessary for atomic intermixing and surface alloying in Pt/Al although the dynamic barrier height is few eV. The mechanism is driven by the local thermalization of the Al(111) surface in a self-organized manner arranged spontaneously by the system without any external stimulus. The core of the short lived thermalized region reaches the local temperature of $\sim 1000$ K (including few tens of Al atoms) while the average temperature of the simulation cell is $\sim 3$ K. The transient facilitated intermixing process also takes place with repulsive impurity-host interaction potential leading to negative atomic mobility hence the atomic injection is largely independent of the strength of the impurity-surface interaction. We predict that similar exotic behaviour is possible in other materials as well.Comment: 12 pages, 8 figures, full paper at: http://www.mfa.kfki.hu/~sule/papers/ptonal.pdf . J. Chem. Phys. (2008), in pres

Education and older adults at the University of the Third Age

This article reports a critical analysis of older adult education in Malta. In educational gerontology, a critical perspective demands the exposure of how relations of power and inequality, in their myriad forms, combinations, and complexities, are manifest in late-life learning initiatives. Fieldwork conducted at the University of the Third Age (UTA) in Malta uncovered the political nature of elder-learning, especially with respect to three intersecting lines of inequality - namely, positive aging, elitism, and gender. A cautionary note is, therefore, warranted at the dominant positive interpretations of UTAs since late-life learning, as any other education activity, is not politically neutral.peer-reviewe

Screening of MAMLD1 Mutations in 70 Children with 46,XY DSD: Identification and Functional Analysis of Two New Mutations

More than 50% of children with severe 46,XY disorders of sex development (DSD) do not have a definitive etiological diagnosis. Besides gonadal dysgenesis, defects in androgen biosynthesis, and abnormalities in androgen sensitivity, the Mastermind-like domain containing 1 (MAMLD1) gene, which was identified as critical for the development of male genitalia, may be implicated. The present study investigated whether MAMLD1 is implicated in cases of severe 46,XY DSD and whether routine sequencing of MAMLD1 should be performed in these patients