Age-induced and photoinduced changes in gene expression profiles in facial skin of Caucasian females across 6 decades of age.

BACKGROUND: Intrinsic and extrinsic factors, including ultraviolet irradiation, lead to visible signs of skin aging. OBJECTIVE: We evaluated molecular changes occurring in photoexposed and photoprotected skin of white women 20 to 74 years of age, some of whom appeared substantially younger than their chronologic age. METHODS: Histologic and transcriptomics profiling were conducted on skin biopsy samples of photoexposed (face and dorsal forearm) or photoprotected (buttocks) body sites from 158 women. 23andMe genotyping determined genetic ancestry. RESULTS: Gene expression and ontologic analysis revealed progressive changes from the 20s to the 70s in pathways related to oxidative stress, energy metabolism, senescence, and epidermal barrier; these changes were accelerated in the 60s and 70s. The gene expression patterns from the subset of women who were younger-appearing were similar to those in women who were actually younger. LIMITATIONS: Broader application of these findings (eg, across races and Fitzpatrick skin types) will require further studies. CONCLUSIONS: This study demonstrates a wide range of molecular processes in skin affected by aging, providing relevant targets for improving the condition of aging skin at different life stages and defining a molecular pattern of epidermal gene expression in women who appear younger than their chronologic age.

Virtual research visits and direct-to-consumer genetic testing in Parkinson's disease.

OBJECTIVE: The purpose of this study was to conduct a proof-of-concept study to evaluate remote recruitment and assessment of individuals ("virtual research visits") with Parkinson's disease who have pursued direct-to-consumer genetic testing. METHODS: Participants in 23andMe's "Parkinson's Research Community" were contacted by 23andMe. Fifty willing participants living in 23 states underwent a remote, standardized assessment including cognitive and motor tests by a neurologist via video conferencing and then completed a survey. Primary outcomes assessed were (a) proportion of participants who completed the remote assessments; (b) level of agreement (using Cohen's kappa coefficient) of patient-reported data with that of a neurologist; and (c) interest in future virtual research visits. RESULTS: The self-reported diagnosis of Parkinson's disease was confirmed in all cases (k = 1.00). The level of agreement for age of symptom onset (k = 0.97) and family history (k = 0.85) was very good but worse for falling (k = 0.59), tremor (k = 0.56), light-headedness (k = 0.31), and urine control (k = 0.15). Thirty-eight (76%) of the 50 participants completed a post-assessment survey, and 87% of respondents said they would be more or much more willing to participate in future clinical trials if they could do research visits remotely. CONCLUSION: Remote clinical assessments of individuals with known genotypes were conducted nationally and rapidly from a single site, confirmed self-reported diagnosis, and were received favorably. Direct-to-consumer genetic testing and virtual research visits together may enable characterization of genotype and phenotype for geographically diverse populations.

Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis.

Despite evidence for heritable variation in cannabis involvement and the discovery of cannabinoid receptors and their endogenous ligands, no consistent patterns have emerged from candidate endocannabinoid (eCB) genetic association studies of cannabis involvement. Given interactions between eCB and stress systems and associations between childhood stress and cannabis involvement, it may be important to consider childhood adversity in the context of eCB-related genetic variation. We employed a system-level gene-based analysis of data from the Comorbidity and Trauma Study (N = 1,558) to examine whether genetic variation in six eCB genes (anabolism: DAGLA, DAGLB, NAPEPLD; catabolism: MGLL, FAAH; binding: CNR1; SNPs N = 65) and childhood sexual abuse (CSA) predict cannabis dependence symptoms. Significant interactions with CSA emerged for MGLL at the gene level (p = .009), and for rs604300 within MGLL (ΔR2 = .007, p < .001), the latter of which survived SNP-level Bonferroni correction and was significant in an additional sample with similar directional effects (N = 859; ΔR2 = .005, p = .026). Furthermore, in a third sample (N = 312), there was evidence that rs604300 genotype interacts with early life adversity to predict threat-related basolateral amygdala habituation, a neural phenotype linked to the eCB system and addiction (ΔR2 = .013, p = .047). Rs604300 may be related to epigenetic modulation of MGLL expression. These results are consistent with rodent models implicating 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid metabolized by the enzyme encoded by MGLL, in the etiology of stress adaptation related to cannabis dependence, but require further replication.