Evaluating the Impact of Oleocanthal and Oleacein on Skin Aging: Results of a Randomized Clinical Study.

The prevalence of skin aging and the request for effective treatments have driven dermatological research towards natural solutions. This study investigates the anti-aging efficacy of two bioactive natural polyphenols, Oleocanthal and Oleacein, in a skincare formulation. A single-blind, randomized clinical trial involved 70 participants, using a comprehensive exclusion criterion to ensure participant safety and study integrity. Participants applied the Oleocanthal and Oleacein 1% serum formulation twice daily for 30 days. The efficacy was objectively assessed using the VISIA® Skin Analysis System at baseline, after 15 days, and after 30 days. Results indicated significant wrinkle reduction in most groups. For women aged 45-79 years, the mean change was -33.91% (95% CI: -46.75% to -21.07%). For men aged 20-44 years, it was -51.93% (95% CI: -76.54% to -27.33%), and for men aged 45-79 years, it was -46.56% (95% CI: -58.32% to -34.81%). For women aged 20-44 years, the change was -25.68% (95% CI: -63.91% to 12.54%), not statistically significant. These findings highlight the potential of EVOO-derived polyphenols in anti-aging skincare, particularly for older adults. This research paves the way for further exploration into natural compounds in dermatology, particularly for aging skin management.

Peripheral Blood Mononuclear Cells (PB-MNCs) for the treatment of chronic tissue dystrophy in a complex case of lower limb reconstruction.

BACKGROUND: Recently, the infiltration of a subpopulation of cells represented by mononucleated cells extracted from peripheral blood [Peripheral Blood-Mononuclear Cells (PB-MNCs)] is becoming a useful technique for medical and surgical regenerative procedures. Due to the angiogenetic and regenerative properties of PB-MNCs, the infiltration of these cells is, in our opinion, a new option indicated in the treatment of pathologies characterized by tissue dystrophy, loss of vascularization, and non-healing wounds. CASE PRESENTATION: A 25-year-old active smoker patient was diagnosed with Rhabdomyosarcoma of the anterior tibial muscle of his left leg and treated with neoadjuvant chemo- and radiotherapy (RT). After the tumor excision, the patient developed wound dehiscence with bone exposure and a perilesional radiation-induced chronic dermatitis characterized by skin dyschromia and hair thinning along the treated area. The patient underwent surgical debridement and reconstruction with autologous skin grafts and dermal substitutes, with poor outcomes due to graft failure. The patient was subsequently treated with surgical debridement and coverage with a reverse sural fascia-cutaneous flap. After 13 days, wound dehiscence was observed, and reconstruction of the dehiscent areas was performed with a split-thickness autologous skin graft with no success. After wound debridement, a new split-thickness skin graft was performed, and a concentrate of autologous PB-MNCs was injected in the flap and perilesional skin. After 14 days, graft take was reached, and improvements in perilesional tissue tropism were noted. At 2 months follow-up, the patient appeared completely healed. CONCLUSIONS: In our opinion, the use of PB-MNCs to treat conditions characterized by tissue dystrophy, which require neoangiogenesis and cell regeneration, can be a useful and unconsidered technique that could be utilized to improve tissue tropism. Furthermore, prospective trials are necessary to validate our observations.

Coffee Intake, Plasma Caffeine Levels, and Kidney Function: Two-Sample Mendelian Randomization Among East Asian and European Ancestries.

Introduction: Previous Mendelian randomization (MR) studies for the coffee-kidney association have reported inconsistent relationships in European populations and never examined mediators of this association. We aimed to evaluate this causal relationship using two-sample MR among both East Asian and European ancestries and to explore underlying mechanisms using plasma caffeine levels. Methods: Among East Asians, the largest genome-wide association study (GWAS) results for coffee intake, plasma caffeine levels, and kidney outcomes were obtained from 152,634; 8940; and 47,070 Japanese adults. Among Europeans, summary statistics were acquired from European GWAS with 428,860; 7719; and 564,470 adults for each trait. We applied different MR methods (inverse-variance weighted [IVW] with random effects, weighted median, weighted mode, and MR-Egger). Results: After excluding possible pleiotropic variants, among East Asian ancestry, drinking an extra coffee intake per week showed a protective association on serum creatinine-based estimated glomerular filtration rate (eGFRcre) (ß = 0.077; 95% confidence interval [CI] = 0.003 to 0.150). Analysis in European ancestry also showed a causal relationship between drinking an extra coffee intake per day and eGFRcre (ß = 0.052; 95% CI = 0.027 to 0.078). These results were consistent across different MR methods accounting for invalid instruments. Higher plasma caffeine levels were associated with lower eGFRcre among both East Asian (ß = -0.071; 95% CI = -0.137 to -0.006) and European ancestries (ß = -0.048; 95% CI = -0.057 to -0.040). Conclusions: Our cross-ancestry MR study found beneficial effects of coffee intake on eGFRcre. However, given the possible adverse effects of plasma caffeine levels on eGFRcre, interpretation of the results should be carefully considered and further investigations on noncaffeine and biological pathways are needed.

Genetic determinants of complement activation in the general population.

Complement is a fundamental innate immune response component. Its alterations are associated with severe systemic diseases. To illuminate the complement's genetic underpinnings, we conduct genome-wide association studies of the functional activity of the classical (CP), lectin (LP), and alternative (AP) complement pathways in the Cooperative Health Research in South Tyrol study (n = 4,990). We identify seven loci, encompassing 13 independent, pathway-specific variants located in or near complement genes (CFHR4, C7, C2, MBL2) and non-complement genes (PDE3A, TNXB, ABO), explaining up to 74% of complement pathways' genetic heritability and implicating long-range haplotypes associated with LP at MBL2. Two-sample Mendelian randomization analyses, supported by transcriptome- and proteome-wide colocalization, confirm known causal pathways, establish within-complement feedback loops, and implicate causality of ABO on LP and of CFHR2 and C7 on AP. LP causally influences collectin-11 and KAAG1 levels and the risk of mouth ulcers. These results build a comprehensive resource to investigate the role of complement in human health.

Asthma and incident coronary heart disease: an observational and Mendelian randomisation study.

BACKGROUND: Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings. METHODS: First, we conducted an observational study using UK medical records to match asthma patients 1:1, by age, sex and general practitioner (GP) practice, to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium (TAGC) and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium (CARDIoGRAM). Using 64 asthma single nucleotide polymorphisms, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy. RESULTS: In our observational study (n=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR 1.06, 95% CI 1.01-1.13); after accounting for healthcare behaviour, we found no association (model 2: HR 0.99, 95% CI 0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR 1.11, 95% CI 1.01-1.21; males: HR 0.91, 95% CI 0.84-0.98). Our MR study (n=589 875) found no association between asthma and CHD (OR 1.01, 95% CI 0.98-1.04) and no modification by sex. CONCLUSIONS: Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.

Fresh vs. frozen embryo transfer in assisted reproductive techniques: a single center retrospective cohort study and ethical-legal implications.

OBJECTIVE: Several studies have shown higher pregnancy rates and better perinatal outcomes with frozen embryo transfers than with fresh techniques, with better results in patients with polycystic ovary syndrome (PCOS) but with a higher rate of pregnancy complications such as preeclampsia. This retrospective cohort study aims to compare the cumulative live birth rates, maternal and neonatal complications of fresh embryo transfers (ET) and frozen-embryo transfers (FET) in infertile women who underwent assisted reproduction techniques (ART) at the Azienda Ospedaliera Ospedali Riuniti (AOOR) Villa Sofia Cervello, Palermo, Italy. In addition, the authors have focused on the legislative and ethical complexities which such a procedure entails. PATIENTS AND METHODS: Out of 475 women undergoing in vitro fertilization programs from January 2017 to January 2021, 128 were enrolled; 70 patients underwent ET, and 58 patients FET. The main outcome measure was live birth rates. Secondary outcomes were clinical pregnancy, ongoing pregnancy, pregnancy loss, low birth weight (LBW), ectopic pregnancy, and obstetrical and perinatal complications. RESULTS: The cumulative live birth rates were similar between the fresh transfer (95.7%) and frozen transfer (93.1%). Biochemical pregnancy rates, clinical pregnancy, ongoing pregnancy, and pregnancy loss were similar between the groups. CONCLUSIONS: Obstetrical outcomes were not statistically different between the two groups; a higher preterm delivery rate was reported in the FET group. ET birth weights were notably lower for singletons compared to the freeze-all strategy. ET patients also had higher LBW rates, with a 2.5-fold higher rate compared to FET. No significant differences were found in cumulative live birth rates between ET and FET, which is consistent with earlier studies. FET protocols are linked to higher neonatal birth weight and lower risk of LBW than fresh ET. The ethical and legal quandaries inherent in such techniques, as technology moves on and outpaces current legislative frameworks, cannot be discounted.

Clinical course and features of persistent polyclonal B-cell lymphocytosis with BCL-6 amplification during pregnancy.

BACKGROUND: Persistent polyclonal B-cell lymphocytosis is a rare nonmalignant disorder characterized by mild persistent lymphocyte proliferation with possible evolution to aggressive lymphoma. Its biology is not well known, but it is characterized by a specific immunophenotype with rearrangement of the BCL-2/IGH gene, whereas amplification of the BCL-6 gene has rarely been reported. Given the paucity of reports, it has been hypothesized that this disorder is associated with poor pregnancy outcomes. CASE REPORT: To our knowledge, only two successful pregnancies have been described in women with this condition. We report the third successful pregnancy in a patient with PPBL and the first with amplification of the BCL-6 gene. CONCLUSIONS: PPBL is still a poorly understood clinical condition with insufficient data to demonstrate an adverse effect on pregnancy. The role of BCL-6 dysregulation in the pathogenesis of PPBL and its prognostic significance are still unknown. Evolution into aggressive clonal lymphoproliferative disorders is possible and prolonged hematologic follow-up is warranted in patients with this rare clinical disorder.

Molecular phenotypes of mitochondrial dysfunction in clinically non-manifesting heterozygous PRKN variant carriers.

Homozygous or compound heterozygous (biallelic) variants in PRKN are causal for PD with highly penetrant symptom expression, while the much more common heterozygous variants may predispose to PD with highly reduced penetrance, through altered mitochondrial function. In the presence of pathogenic heterozygous variants, it is therefore important to test for mitochondrial alteration in cells derived from variant carriers to establish potential presymptomatic molecular markers. We generated lymphoblasts (LCLs) and human induced pluripotent stem cell (hiPSC)-derived neurons from non-manifesting heterozygous PRKN variant carriers and tested them for mitochondrial functionality. In LCLs, we detected hyperactive mitochondrial respiration, and, although milder compared to a biallelic PRKN-PD patient, hiPSC-derived neurons of non-manifesting heterozygous variant carriers also displayed several phenotypes of altered mitochondrial function. Overall, we identified molecular phenotypes that might be used to monitor heterozygous PRKN variant carriers during the prodromal phase. Such markers might also be useful to identify individuals at greater risk of eventual disease development and for testing potential mitochondrial function-based neuroprotective therapies before neurodegeneration advances.

The causal relationship between gastro-oesophageal reflux disease and idiopathic pulmonary fibrosis: a bidirectional two-sample Mendelian randomisation study.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is associated with idiopathic pulmonary fibrosis (IPF) in observational studies. It is not known if this association arises because GORD causes IPF or because IPF causes GORD, or because of confounding by factors, such as smoking, associated with both GORD and IPF. We used bidirectional Mendelian randomisation (MR), where genetic variants are used as instrumental variables to address issues of confounding and reverse causation, to examine how, if at all, GORD and IPF are causally related. METHODS: A bidirectional two-sample MR was performed to estimate the causal effect of GORD on IPF risk and of IPF on GORD risk, using genetic data from the largest GORD (78 707 cases and 288 734 controls) and IPF (4125 cases and 20 464 controls) genome-wide association meta-analyses currently available. RESULTS: GORD increased the risk of IPF, with an OR of 1.6 (95% CI 1.04-2.49; p=0.032). There was no evidence of a causal effect of IPF on the risk of GORD, with an OR of 0.999 (95% CI 0.997-1.000; p=0.245). CONCLUSIONS: We found that GORD increases the risk of IPF, but found no evidence that IPF increases the risk of GORD. GORD should be considered in future studies of IPF risk and interest in it as a potential therapeutic target should be renewed. The mechanisms underlying the effect of GORD on IPF should also be investigated.

Chronic graft vs. host disease and hypogammaglobulinemia predict a lower immunological response to the BNT162b2 mRNA COVID-19 vaccine after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Due to the high mortality rate of COVID-19, the assessment of BNT162b2 SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) efficacy in allogeneic hematopoietic stem cell transplant (HSCT) recipients is mandatory. PATIENTS AND METHODS: We conducted a single-center pilot study with the main objective of evaluating the immunogenicity of the BNT162b2 mRNA vaccine in 31 hematological patients who underwent hematopoietic stem cell transplantation within the previous 12 months and/or were affected by chronic graft-vs.-host-disease (cGVHD), by the assessment of antibody levels at 30-45 days after the second dose of vaccine. RESULTS: After the second dose of vaccine, 23 out of 31 patients (74%) showed a positive immune response. The presence of severe cGVHD or Ig deficiency identified 7 out of 8 (85%) of non-responders. The median absolute cluster of differentiation 19 (CD19) count was significantly lower in non-responders vs. responders (109/µl vs. 351/µl). Underlying pathology, comorbidities, type of donor, time intervals from transplant and cluster of differentiation 3/cluster of differentiation 4/cluster of differentiation 8 (CD3/CD4/CD8) subsets were not significantly associated with an effective immune response to vaccination. CONCLUSIONS: Despite the limited sample of patients enrolled, our findings suggest that hypogammaglobulinemia and cGVHD could be associated with poor humoral response to the BNT162b2.

Pyoderma Gangrenosum and inflammatory bowel disease: a combined medical and surgical approach - case report and literature review.

OBJECTIVE: Pyoderma Gangrenosum (PG) is an immune-mediated neutrophilic dermatosis, characterized by large painful ulcers occurring in various body segments. It can be associated to Inflammatory Bowel Disease (IBD) including both Ulcerative Colitis and Crohn Disease. Prompt and effective management is fundamental, due to its high morbidity and mortality rates. By presenting our clinical experience, we aimed at showing the efficacy of a combined therapeutic approach, in which the best of every specialty cooperates managing this hazardous disease. PATIENTS AND METHODS: We report on two patients attending our outpatient clinic with ulcerative skin lesions at the level of the back. Patient 1 suffered from Crohn disease and Patient 2 presented a positive history of abdominal pain, diarrhea with mucus and blood in the stool. Histological exam was performed with final diagnosis of PG associated with IBD. A Literature review was carried out in order to highlight the role of combined clinical-surgical management of PG in adult patients with IBD. RESULTS: Complete resolution of the lesions was achieved in 4 months and 3 months for each patient respectively without relapse. PubMed was searched from 2000 to 2020 with the following keywords: (Pyoderma) AND/OR (Pyoderma Gangrenosum) AND (Inflammatory Bowel Disease) AND/OR (Ulcerative Colitis) AND/OR (Crohn Disease) AND (Management). Seven papers were included (4 case reports, 2 case series, 1 comprehensive review) and reviewed using a descriptive checklist. CONCLUSIONS: PG should be treated by dedicated multidisciplinary teams, in which every specialist plays a crucial role from the diagnosis to the treatment and up to the long-term follow-up.

Whole Exome Sequencing Enhanced Imputation Identifies 85 Metabolite Associations in the Alpine CHRIS Cohort.

Metabolites are intermediates or end products of biochemical processes involved in both health and disease. Here, we take advantage of the well-characterized Cooperative Health Research in South Tyrol (CHRIS) study to perform an exome-wide association study (ExWAS) on absolute concentrations of 175 metabolites in 3294 individuals. To increase power, we imputed the identified variants into an additional 2211 genotyped individuals of CHRIS. In the resulting dataset of 5505 individuals, we identified 85 single-variant genetic associations, of which 39 have not been reported previously. Fifteen associations emerged at ten variants with >5-fold enrichment in CHRIS compared to non-Finnish Europeans reported in the gnomAD database. For example, the CHRIS-enriched ETFDH stop gain variant p.Trp286Ter (rs1235904433-hexanoylcarnitine) and the MCCC2 stop lost variant p.Ter564GlnextTer3 (rs751970792-carnitine) have been found in patients with glutaric acidemia type II and 3-methylcrotonylglycinuria, respectively, but the loci have not been associated with the respective metabolites in a genome-wide association study (GWAS) previously. We further identified three gene-trait associations, where multiple rare variants contribute to the signal. These results not only provide further evidence for previously described associations, but also describe novel genes and mechanisms for diseases and disease-related traits.

A Mendelian randomization study investigating the causal role of inflammation on Parkinson's disease.

There is increasing evidence for inflammation as a determinant in the pathogenesis of Parkinson's disease, but its role in parkinsonian neurodegeneration remains elusive. It is not clear whether inflammatory cascades are causes or consequences of dopamine neuron death. In the present study, we aim to perform an in-depth statistical investigation of the causal relationship between inflammation and Parkinson's disease using a two-sample Mendelian randomization design. Genetic instruments were selected using summary-level data from the largest genome-wide association studies to date (sample size ranging from 13 955 to 204 402 individuals) conducted on a European population for the following inflammation biomarkers: C-reactive protein, interleukin-6, interleukin 1 receptor antagonist and tumour necrosis factor α. Genetic association data on Parkinson's disease (56 306 cases and 1 417 791 controls) and age at onset of Parkinson's disease (28 568 cases) were obtained from the International Parkinson's Disease Genomics Consortium. On primary analysis, causal associations were estimated on sets of strong (P-value < 5 × 10-8; F-statistic > 10) and independent (linkage disequilibrium r2 < 0.001) genetic instruments using the inverse-variance weighted method. In sensitivity analysis, we estimated causal effects using robust Mendelian randomization methods and after removing pleiotropic genetic variants. Reverse causation was also explored. We repeated the analysis on different data sources for inflammatory biomarkers to check the consistency of the findings. In all the three data sources selected for interleukin-6, we found statistical evidence for an earlier age at onset of Parkinson's disease associated with increased interleukin-6 concentration [years difference per 1 log-unit increase = -2.364, 95% confidence interval (CI) = -4.789-0.060; years difference per 1 log-unit increase = -2.011, 95% CI = -3.706 to -0.317; years difference per 1 log-unit increase = -1.569, 95% CI = -2.891 to -0.247]. We did not observe any statistical evidence for causal effects of C-reactive protein, interleukin 1 receptor antagonist and tumour necrosis factor α on both Parkinson's disease and its age at onset. Results after excluding possible pleiotropic genetic variants were consistent with findings from primary analyses. When investigating reverse causation, we did not find evidence for a causal effect of Parkinson's disease or age at onset on any biomarkers of inflammation. We found evidence for a causal association between the onset of Parkinson's disease and interleukin-6. The findings of this study suggest that the pro-inflammatory activity of the interleukin-6 cytokine could be a determinant of prodromal Parkinson's disease.

Monocarboxylate transporter 1 deficiency impacts CD8+ T lymphocytes proliferation and recruitment to adipose tissue during obesity.

Lactate sits at the crossroad of metabolism, immunity, and inflammation. The expression of cellular lactate transporter MCT1 (known as Slc16a1) increases during immune cell activation to cope with the metabolic reprogramming. We investigated the impact of MCT1 deficiency on CD8+ T cell function during obesity-related inflammatory conditions. The absence of MCT1 impaired CD8+ T cell proliferation with a shift of ATP production to mitochondrial oxidative phosphorylation. In Slc16a1 f/f Tcell cre mice fed a high-fat diet, a reduction in the number of CD8+ T cells, which infiltrated epididymal visceral adipose tissue (epiWAT) or subcutaneous adipose tissue, was observed. Adipose tissue weight and adipocyte area were significantly reduced together with downregulation of adipogenic genes only in the epiWAT. Our findings highlight a distinct effect of MCT1 deficiency in CD8+ T cells in the crosstalk with adipocytes and reinforce the concept that targeting immunometabolic reprogramming in lymphocyte could impact the immune-adipose tissue axis in obesity.

Update on fertility preservation: new opportunities and challenges in the fight against infertility.

Abstract: Infertility has been characterized as a disease by the World Health Organization (WHO) and reportedly affects about 10-12% of couples worldwide, while the incidence is even higher in Italy, at about 15%. The issue of iatrogenic infertility arising from treatments that can compromise an individual's reproductive capacity, it is necessary to inform patients of the possible damage on their future fertility and on the possibilities to preserve it. The complexities inherent in the various techniques and approaches aimed at preserving fertility should be expounded upon thoroughly to the patients, who should also receive proper psychological assistance and counseling, which ought to take into account the ethical distinctive challenges and the possible misgivings that may be caused in patients. Ovarian Tissue Cryopreservation (OTC) and ovarian tissue transplantation (OTT) can constitute a valuable part of the clinical armamentarium for preserving fertility, although the data are still inconclusive, particularly in over-36 patients. The multidisciplinary nature of the healthcare teams involved in such interventions is of paramount importance to optimize results.

Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology.

Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.

A multi-omics study of circulating phospholipid markers of blood pressure.

High-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The associations of blood pressure and 151 plasma phospholipids measured by electrospray ionization tandem mass spectrometry were performed by linear regression in five European cohorts (n = 2786 in discovery and n = 1185 in replication). We further explored the blood pressure-related phospholipids in Erasmus Rucphen Family (ERF) study by associating them with multiple cardiometabolic traits (linear regression) and predicting incident hypertension (Cox regression). Mendelian Randomization (MR) and phenome-wide association study (Phewas) were also explored to further investigate these association results. We identified six phosphatidylethanolamines (PE 38:3, PE 38:4, PE 38:6, PE 40:4, PE 40:5 and PE 40:6) and two phosphatidylcholines (PC 32:1 and PC 40:5) which together predicted incident hypertension with an area under the ROC curve (AUC) of 0.61. The identified eight phospholipids are strongly associated with triglycerides, obesity related traits (e.g. waist, waist-hip ratio, total fat percentage, body mass index, lipid-lowering medication, and leptin), diabetes related traits (e.g. glucose, insulin resistance and insulin) and prevalent type 2 diabetes. The genetic determinants of these phospholipids also associated with many lipoproteins, heart rate, pulse rate and blood cell counts. No significant association was identified by bi-directional MR approach. We identified eight blood pressure-related circulating phospholipids that have a predictive value for incident hypertension. Our cross-omics analyses show that phospholipid metabolites in the circulation may yield insight into blood pressure regulation and raise a number of testable hypothesis for future research.

Systematic review of Mendelian randomization studies on Parkinson's disease.

Background: Parkinson's disease (PD) is known to be associated with non-genetic factors. To infer causality, Mendelian randomization (MR) studies are increasingly used. Here, genetic variants are used as instrumental variables for the risk factor but have no direct effect on PD themselves. Methods: We performed a systematic literature review on MR studies for PD. Studies were identified searching the PubMed database. Upon data extraction, we evaluated the methodological quality and summarized the evidence. Results: Twelve articles were included. Most studies showed "good" methodological quality, but most did not report proper power estimations. Twelve analyses yielded nominally significant effects. Conclusions: Our systematic review shows that most MR studies were well performed and allow to identify causal exposures, which may inform further studies on the prevention and early intervention of PD.