Genome-wide association study of anterior uveitis.

Background/aims: The purpose of this study is to define genetic factors associated with anterior uveitis through genome-wide association study (GWAS).

Methods: In this GWAS meta-analysis, we combined data from the FinnGen, Estonian Biobank and UK Biobank with a total of 12 205 anterior uveitis cases and 917 145 controls. We performed a phenome-wide association study (PheWAS) to investigate associations across phenotypes and traits.

Personalized Profiling of Lipoprotein and Lipid Metabolism Based on 1018 Measures from Combined Quantitative NMR and LC-MS/MS Platforms.

Applications of advanced omics methodologies are increasingly popular in biomedicine. However, large-scale studies aiming at clinical translation are typically siloed to single technologies. Here, we present the first comprehensive large-scale population data combining 209 lipoprotein measures from a quantitative NMR spectroscopy platform and 809 lipid classes and species from a quantitative LC-MS/MS platform.

Understanding lipidomics associations and the lipoprotein-related caveats in population epidemiology.

Mass spectrometry lipidomics is becoming customary to analyse serum/plasma samples in epidemiology. The measurables are molecular constituents of lipoprotein particles, but very little is known on the consequences of adjusting lipidomics data with lipoprotein measures. We studied two population cohorts with 5,657 and 2,036 participants.

GLS2 links glutamine metabolism and atherosclerosis by remodeling artery walls.

Metabolic dysregulation, including perturbed glutamine-glutamate homeostasis, is common among patients with cardiovascular diseases, but the underlying mechanisms remain largely unknown. Using the human MESA cohort, here we show that plasma glutamine-glutamate ratio is an independent risk factor for carotid plaque progression. Mice deficient in glutaminase-2 (Gls2), the enzyme that mediates hepatic glutaminolysis, developed accelerated atherosclerosis and susceptibility to catastrophic cardiac events, while Gls2 overexpression partially protected from disease progression.

Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations.

Given that lumbar disc herniation (LDH) is a prevalent spinal condition that causes significant individual suffering and societal costs, the genetic basis of LDH has received relatively little research. Our aim is to increase understanding of the genetic factors influencing LDH. We perform a genome-wide association analysis (GWAS) of LDH in the FinnGen project and in Estonian and UK biobanks, followed by a genome-wide meta-analysis to combine the results.

Genome-wide association study indicates novel associations of annexin A13 to secretory and GAS2L2 with mucous otitis media.

To evaluate the genetics of chronic nonsuppurative otitis media (OM). We performed a genome-wide association study of 429,599 individuals included in the FinnGen study using three different case definitions: combined chronic nonsuppurative OM (7034 cases) (included serous and mucous chronic OM), mucous chronic OM (5953 cases), and secretory chronic OM (1689 cases). Individuals without otitis media were used as controls (417,745 controls).

Does previous total hip arthroplasty affect the outcomes of total knee arthroplasty? A one- and five-year follow-up registry study in a monocentric hospital.

Background: Osteoarthritis in the lower extremities becomes more common as people age. In addition to conservative treatments, hip or knee arthroplasty is often needed. The aim of this study was to evaluate total knee arthroplasty (later TKA) in patients, comparing those who had previously undergone THA (later THA/TKA), with those who had not undergone such procedure.

Cone-beam computed tomography imaging and three-dimensional analysis of midfoot joints during non-weightbearing and weightbearing in 11 healthy feet.

Background: Studies report that Lisfranc injury is more common than thought. Several imaging methods for assessing the stability of Lisfranc injury have been described but many are impossible to standardize and not accurate enough.

Purpose: To present a three-dimensional (3D) method for analyzing the changes in the joint space width of the midfoot joint and the joints of the medial part of the Lisfranc complex in healthy individuals.

Precision treatment of beta-cell monogenic diabetes: a systematic review.

Background: Beta-cell monogenic forms of diabetes have strong support for precision medicine. We systematically analyzed evidence for precision treatments for GCK-related hyperglycemia, HNF1A-, HNF4A- and HNF1B-diabetes, and mitochondrial diabetes (MD) due to m.3243 A > G variant, 6q24-transient neonatal diabetes mellitus (TND) and SLC19A2-diabetes.

Novel Genetic Variants Associated with Primary Myocardial Fibrosis in Sudden Cardiac Death Victims.

Myocardial fibrosis is a common finding in victims of sudden cardiac death (SCD). Whole exome sequencing was performed in 127 victims of SCD with primary myocardial fibrosis as the only pathological finding. These cases are derived from the Fingesture study which has collected data from autopsy-verified SCD victims in Northern Finland.

Human iPSC and CRISPR targeted gene knock-in strategy for studying the somatic TIE2 mutation in endothelial cells.

Induced pluripotent stem cell (iPSC) derived endothelial cells (iECs) have emerged as a promising tool for studying vascular biology and providing a platform for modelling various vascular diseases, including those with genetic origins. Currently, primary ECs are the main source for disease modelling in this field. However, they are difficult to edit and have a limited lifespan.

Identifying Atopic Dermatitis Risk Loci in 1,094,060 Individuals with Subanalysis of Disease Severity and Onset.

Atopic dermatitis (AD) is a common inflammatory skin disease highly attributable to genetic factors. In this study, we report results from a genome-wide meta-analysis of AD in 37,541 cases and 1,056,519 controls with data from the FinnGen project, the Estonian Biobank, the UK Biobank, the EAGLE Consortium, and the BioBank Japan. We detected 77 independent AD-associated loci, of which 10 were, to our knowledge, previously unreported.

Clinical and biochemical associations of urinary metabolites: quantitative epidemiological approach on renal-cardiometabolic biomarkers.

Background: Urinary metabolomics has demonstrated considerable potential to assess kidney function and its metabolic corollaries in health and disease. However, applications in epidemiology remain sparse due to technical challenges.

Methods: We added 17 metabolites to an open-access urinary nuclear magnetic resonance metabolomics platform, extending the panel to 61 metabolites (n = 994).

Simultaneous bilateral versus unilateral total hip arthroplasty: Pain and physical function in a one- and five-year follow-up - retrospective patients record study.

Background: Total hip arthroplasty (THA) decreases pain and improves function in patients with osteoarthritis. In some cases, both hips have been operated simultaneously. Our aim was to report patients' pain and physical function after one- and five-years post-operatively among patients who underwent unilateral THA and those who underwent bilateral THA at the same time in one orthopaedic hospital in Finland.

Low and high serum IgG associates with respiratory infections in a young and working age population.

Background: We investigated health consequences and genetic properties associated with serum IgG concentration in a young and working age general population.

Methods: Northern Finland Birth Cohort 1966 (NFBC1966, n = 12,231) health data have been collected from birth to 52 years of age. Relationships between life-long health events, medications, chronic conditions, lifestyle, and serum IgG concentration measured at age 46 years (n = 5430) were analysed.

Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy.

Importance: A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.

Objective: To disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.

Design, Setting, And Participants: This GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders.

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes.

Background: Beta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for precision medicine. We reviewed treatment of hyperglycemia in GCK-related hyperglycemia, HNF1A-HNF4A- and HNF1B-diabetes, Mitochondrial diabetes (MD) due to m.3243A>G variant, 6q24-transient neonatal diabetes (TND) and SLC19A2-diabetes.

Risk factors for revision due to prosthetic joint infection following total knee arthroplasty based on 62,087 knees in the Finnish Arthroplasty Register from 2014 to 2020.

Background And Purpose: Periprosthetic joint infection (PJI) is the commonest reason for revision after total knee arthroplasty (TKA). We assessed the risk factors for revision due to PJI following TKA based on the Finnish Arthroplasty Register (FAR).

Patients And Methods: We analyzed 62,087 primary condylar TKAs registered between June 2014 and February 2020 with revision for PJI as the endpoint.