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.

Traumatic life events as predictors for depression in middle-aged men and women: A Finnish twin study.

Background: We examined exposure to adulthood traumatic life events (TLEs) and their associations with depression in women and men. Then we examined whether those associations are independent of exposure loading and vulnerability including familial confounding.

Methods: The fourth survey in 2011 of the population-based Finnish Twin Cohort had 8410 participants (45 % men, mean age 60 years).

Development and evaluation of a web-based diet quality screener for vegans (VEGANScreener): a cross-sectional, observational, multicenter, clinical study.

Consumption of plant-based diets, including vegan diets, necessitates attention to the quality of the diet for the prevention and early detection of nutritional deficiencies. Within the VEGANScreener project, a unique brief screening tool for the assessment and monitoring of diet quality among vegans in Europe was developed. To provide a standardized tool for public use, a clinical study will be conducted to evaluate the VEGANScreener against a reference dietary assessment method and nutritional biomarkers.

Cancer incidence following non-neoplastic medical conditions: a prospective population-based cohort study.

Background And Purpose: Many non-neoplastic diseases have been established to be tumorigenic, and cancers are sometimes misdiagnosed as non-neoplastic diseases. We conducted a comprehensive registry-based study of site-specific cancer diagnosis risk following the diagnosis of any preceding medical condition (PMC) encoded by the International Classification of Diseases (ICD)-10 classification.

Material And Methods: We analyzed healthcare data and cancer data for a random population-based sample of 2.

A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery.

The gene-regulatory dynamics governing drug responses in cancer are yet to be fully understood. Here, we report a pipeline capable of producing high-throughput pharmacotranscriptomic profiling through live-cell barcoding using antibody-oligonucleotide conjugates. This pipeline combines drug screening with 96-plex single-cell RNA sequencing.

Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer.

Epithelial tumors are characterized by abundant inter- and intra-tumor heterogeneity, which complicates diagnostics and treatment. The contribution of cancer-stroma interactions to this heterogeneity is poorly understood. Here, we report a paradigm to quantify phenotypic diversity in head and neck squamous cell carcinoma (HNSCC) with single-cell resolution.

Exposure to antibiotics and risk of latent autoimmune diabetes in adults and type 2 diabetes: results from a Swedish case-control study (ESTRID) and the Norwegian HUNT study.

Aims/hypothesis: Some studies find an increased risk of type 1 diabetes in children exposed to antibiotics. We investigated if exposure to antibiotics increases the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes.

Methods: We used data from a Swedish case-control study (Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes [ESTRID]: LADA, n=597; type 2 diabetes, n=2065; control participants matched on participation time, n=2386) and a case-control study nested within the Norwegian Trøndelag Health Study (HUNT) (n=82/1279/2050).

Y chromosome sequencing data suggest dual paths of haplogroup N1a1 into Finland.

The paternally inherited Y chromosome is highly informative of genetic ancestry, therefore making it useful in studies of population history. In Finland, two Y-chromosomal haplogroups reveal the major substructure of the population: N1a1 enriched in the northeast and I1a in the southwest, suggested to reflect eastern and western ancestry contributions to the population. Yet, beyond these major Y-chromosomal lineages, the distribution of finer-scale Y-chromosomal variation has not been assessed in Finland.

Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far.

Venetoclax triggers sublethal apoptotic signaling in venetoclax-resistant acute myeloid leukemia cells and induces vulnerability to PARP inhibition and azacitidine.

Venetoclax plus azacitidine treatment is clinically beneficial for elderly and unfit acute myeloid leukemia (AML) patients. However, the treatment is rarely curative, and relapse due to resistant disease eventually emerges. Since no current clinically feasible treatments are known to be effective at the state of acquired venetoclax resistance, this is becoming a major challenge in AML treatment.

Maternal psychological distress and temperament traits in children from infancy to late childhood.

Background: Maternal psychological distress during pregnancy is associated with infant temperament. Whether associations persist into late childhood, whether maternal distress is associated with temperament change from infancy to late childhood, whether associations are independent of maternal concurrent distress, and whether maternal distress has sensitive exposure periods on child temperament remain unclear.

Methods: Our study includes mother-child dyads from Finnish, prospective Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study.

Association Between Accelerometer-Measured Physical Activity and Mobility Limitations in Twins.

Background: The associations between mobility limitations and device-measured physical activity are sparsely studied. In this study, these associations are studied among community-dwelling older twins.

Methods: This cross-sectional study utilized data gathered in 2014-2016 for the MOBILETWIN study.

Fine-mapping a genome-wide meta-analysis of 98,374 migraine cases identifies 181 sets of candidate causal variants.

Migraine is a highly prevalent neurovascular disorder for which genome-wide association studies (GWAS) have identified over one hundred risk loci, yet the causal variants and genes remain mostly unknown. Here, we meta-analyzed three migraine GWAS including 98,374 cases and 869,160 controls and identified 122 independent risk loci of which 35 were new. Fine-mapping of a meta-analysis is challenging because some variants may be missing from some participating studies and accurate linkage disequilibrium (LD) information of the variants is often not available.

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.