Publications by authors named "Palotie A"
To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.
View Article and Find Full Text PDFBackground: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes.
Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.
Article Synopsis
- * A large study involving nearly 10,000 DCM cases and close to a million controls identified 70 significant genetic locations linked to the disease, revealing the importance of heart muscle cells in its development.
- * The research also indicates that factors like higher body weight and blood pressure may contribute to DCM, and genetic risk scores can help predict the condition across different populations.
Female infertility is a common and complex health problem affecting millions of women worldwide. While multiple factors can contribute to this condition, the underlying cause remains elusive in up to 15%-30% of affected individuals. In our large genome-wide association study (GWAS) of 22,849 women with infertility and 198,989 control individuals from the Finnish population cohort FinnGen, we unveil a landscape of genetic factors associated with the disorder.
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- * The research identified 12 significant genetic markers linked to MG, with certain markers associated specifically with early-onset (under 50) and late-onset (50 and older) forms of the disease.
- * Additionally, the study highlighted the potential role of genetic factors in determining the age of disease onset and demonstrated that polygenic risk scores could help predict MG status, explaining over 4% of the variation in disease presence.
Article Synopsis
- In Finland, isolated cleft palate (CP) occurs more frequently than cleft lip with or without cleft palate (CL/P), which is the opposite trend seen in other European countries.
- A genome-wide association study revealed a specific single nucleotide polymorphism (rs570516915) strongly linked to CP in the Finnish population, showing significant statistical results and confirmed in other cohorts.
- The risk allele for rs570516915 disrupts a binding site for the IRF6 transcription factor, leading to decreased IRF6 expression, indicating that this genetic alteration may be a key factor in the mechanism causing CP.
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.
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- Traumatic brain injury (TBI) is a big problem worldwide, causing many deaths and disabilities, and there aren't great treatments to help recovery.
- Researchers studied whether TBI shares similar causes with other brain conditions, like Alzheimer's and schizophrenia, to find new treatment ideas.
- They found specific brain pathways related to TBI recovery that might also be important for those other conditions, especially pathways dealing with important brain chemicals like serotonin and acetylcholine.
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.
Article Synopsis
- * A meta-analysis identified eight genetic loci linked to Raynaud's syndrome, with specific genes like ADRA2A, NOS3, and IRX1 showing important roles in blood vessel behavior and gene expression.
- * The research utilized CRISPR gene editing and functional assays, revealing how these genes influence blood vessel contraction in response to cold, emphasizing the complexity of genes in understanding this syndrome.
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.
Article Synopsis
- Circulating plasma proteins are crucial for human health and can help measure biological age, which may predict risks for age-related diseases and overall mortality.
- A study using data from the UK Biobank identified 204 proteins that accurately predict chronological age and are linked to 18 chronic diseases, as well as various health measures such as cognitive function and frailty.
- The findings were validated in studies from China and Finland, showing that this proteomic age clock can reliably assess age-related health risks across different populations.
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).
View Article and Find Full Text PDFA diagnosis of epilepsy has significant consequences for an individual but is often challenging in clinical practice. Novel biomarkers are thus greatly needed. Here, we investigated how common genetic factors (epilepsy polygenic risk scores, [PRSs]) influence epilepsy risk in detailed longitudinal electronic health records (EHRs) of > 700k Finns and Estonians.
View Article and Find Full Text PDFThe population of Russia consists of more than 150 local ethnicities. The ethnic diversity and geographic origins, which extend from eastern Europe to Asia, make the population uniquely positioned to investigate the shared properties of inherited disease risks between European and Asian ancestries. We present the analysis of genetic and phenotypic data from a cohort of 4,145 individuals collected in three metro areas in western Russia.
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- In Finland, isolated cleft palate (CP) occurs more frequently than cleft lip with or without cleft palate (CL/P), which is the opposite trend seen in other European nations.
- A genome-wide association study identified a specific SNP (rs570516915) that is strongly linked to CP in the Finnish and Estonian populations.
- This SNP disrupts a binding site for the transcription factor IRF6, leading to decreased enhancer activity and impaired autoregulation, which may contribute to the increased risk of CP.
Article Synopsis
- Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
- They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
- Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
Article Synopsis
- Mosaic loss of the X chromosome (mLOX) is a common genetic alteration in female leukocytes, found in 12% of a study involving 883,574 female participants, with around 2% of their leukocytes showing this alteration.
- Female individuals with mLOX have a higher risk of developing myeloid and lymphoid leukemias, and genetic studies revealed 56 common variants linked to mLOX, pointing towards genes involved in chromosomal errors and diseases.
- The research also found specific rare genetic variants that significantly increase the risk of mLOX and demonstrated how certain X chromosome alleles are preferentially retained, suggesting that both genetic predispositions and selective pressures play a role in the development and growth
Polygenic scores (PGSs) offer the ability to predict genetic risk for complex diseases across the life course; a key benefit over short-term prediction models. To produce risk estimates relevant to clinical and public health decision-making, it is important to account for varying effects due to age and sex. Here, we develop a novel framework to estimate country-, age-, and sex-specific estimates of cumulative incidence stratified by PGS for 18 high-burden diseases.
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- The TWINGEN study aims to identify individuals at high risk for Alzheimer's disease (AD) by assessing various cognitive and health-related factors through an observational clinical recall and biomarker analysis.
- The study involves around 800 participants, gathering data through blood samples, questionnaires, and wearable technology for lifestyle metrics, while also including a smaller group for in-person assessments.
- All data collected will be integrated with existing Finnish biobank records and utilized for further research, following ethical guidelines set by relevant authorities.
Individuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Using whole-exome or whole-genome sequencing of 1,051 individuals with T1D, we aimed to find rare and low-frequency genomic variants associated with stroke in T1D. We analysed the genome comprehensively with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters.
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- The study investigates the genetic basis of supraventricular tachycardias, focusing on atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways/reciprocating tachycardia (AVAP/AVRT).
- Through multiancestry meta-analyses of genome-wide association studies, researchers identified significant genetic loci associated with AVNRT and AVAP/AVRT, implicating specific genes in these cardiac conditions.
- The results suggest that gene regions related to ion channels and cardiac development play crucial roles in susceptibility to supraventricular tachycardias, potentially influencing other cardiovascular issues such as atrial fibrillation