Genetics of hypertension-related sex differences and hypertensive disorders of pregnancy.

Hypertension and hypertensive disorders of pregnancy (HDP) cause a significant burden of disease on societies and individuals by increasing cardiovascular disease risk. Environmental risk factors alone do not explain the observed sexual dimorphism in lifetime blood pressure (BP) trajectories nor inter-individual variation in HDP risk. In this short review, we focus on the genetics of hypertension-related sex differences and HDP and discuss the importance of genetics utilization for sex-specific hypertension risk prediction.

Association between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery: a multi-ancestry study in 10 960 individuals from 9 biobanks.

Obesity is a significant public health concern. GLP-1 receptor agonists (GLP1-RA), predominantly in use as a type 2 diabetes treatment, are a promising pharmacological approach for weight loss, while bariatric surgery (BS) remains a durable, but invasive, intervention. Despite observed heterogeneity in weight loss effects, the genetic effects on weight loss from GLP1-RA and BS have not been extensively explored in large sample sizes, and most studies have focused on differences in race and ethnicity, rather than genetic ancestry.

Novel epigenetic biomarkers for hematopoietic cancer found in twins.

Background And Purpose: This article aims to identify epigenetic markers and detect early development of hematopoietic malignancies through an epigenome wide association study of DNA methylation data.

Materials And Methods: This register-based study includes 1,085 Danish twins with 31 hematopoietic malignancies and methylation levels from 450,154 5'-C-phospate-G-3' (CpG) sites. Associations between methylation levels and incidence of hematopoietic malignancy is studied through time-to-event regression.

Evidence of survival bias in the association between and age at ischemic stroke onset.

Introduction: Large genome-wide association studies (GWASs) using case-control study designs have now identified tens of loci associated with ischemic stroke (IS). As a complement to these studies, we performed GWAS in a case-only design to identify loci influencing the age at onset (AAO) of ischemic stroke.

Methods: Analyses were conducted in a discovery cohort of 10,857 ischemic stroke cases using a linear regression framework.

Overactive mitochondrial DNA replication disrupts perinatal cardiac maturation.

High mitochondrial DNA (mtDNA) amount has been reported to be beneficial for resistance and recovery of metabolic stress, while increased mtDNA synthesis activity can drive aging signs. The intriguing contrast of these two mtDNA boosting outcomes prompted us to jointly elevate mtDNA amount and frequency of replication in mice. We report that high activity of mtDNA synthesis inhibits perinatal metabolic maturation of the heart.

Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study.

Background: Inter-individual differences in treatment response are marked in multiple sclerosis (MS). This is true for Natalizumab (NTZ), to which a subset of patients displays sub-optimal treatment response. We conducted a multi-centric genome-wide association study (GWAS), with additional pathway and network analysis to identify genetic predictors of response to NTZ.

High Burden of Ileus and Pneumonia in Clozapine-Treated Individuals With Schizophrenia: A Finnish 25-Year Follow-Up Register Study.

Objective: The authors used longitudinal biobank data with up to 25 years of follow-up on over 2,600 clozapine users to derive reliable estimates of the real-world burden of clozapine adverse drug events (ADEs).

Methods: A total of 2,659 participants in the FinnGen biobank project had a schizophrenia diagnosis and clozapine purchases with longitudinal electronic health record follow-up for up to 25 years after clozapine initiation. Diseases and health-related events enriched during clozapine use were identified, adjusting for disease severity.

Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles.

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic).

Targeting the Tie-2 Receptor With Faricimab in Central Serous Chorioretinopathy: A Case Series Motivated by a Genetic Finding.

Purpose: To investigate the effects of faricimab, a bispecific antibody targeting VEGF and Ang-2 (thus increasing Tie-2 activity), in patients with CSC based on a recent genetic study that implicated Tie-2 signaling in CSC pathophysiology.

Design: A retrospective interventional multicenter case series.

Methods: We included patients with chronic CSC (persistent or recurrent SRF for ≥6 months) who received at least one faricimab 6 mg injection between January 1 2022, and April 1 2024,.

The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.

The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls.

Associations between gut microbiota and incident fractures in the FINRISK cohort.

The gut microbiota (GM) can regulate bone mass, but its association with incident fractures is unknown. We used Cox regression models to determine whether the GM composition is associated with incident fractures in the large FINRISK 2002 cohort (n = 7043, 1092 incident fracture cases, median follow-up time 18 years) with information on GM composition and functionality from shotgun metagenome sequencing. Higher alpha diversity was associated with decreased fracture risk (hazard ratio [HR] 0.

Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort.

Background And Objectives: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH).

Methods: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records.